CA2801459C - Lipidomic biomarkers for identification of high-risk coronary artery disease patients - Google Patents
Lipidomic biomarkers for identification of high-risk coronary artery disease patients Download PDFInfo
- Publication number
- CA2801459C CA2801459C CA2801459A CA2801459A CA2801459C CA 2801459 C CA2801459 C CA 2801459C CA 2801459 A CA2801459 A CA 2801459A CA 2801459 A CA2801459 A CA 2801459A CA 2801459 C CA2801459 C CA 2801459C
- Authority
- CA
- Canada
- Prior art keywords
- cer
- total
- apolipoprotein
- lipid
- cholesterol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 208000029078 coronary artery disease Diseases 0.000 title claims description 32
- 239000000090 biomarker Substances 0.000 title description 18
- 150000002632 lipids Chemical class 0.000 claims abstract description 219
- 238000000034 method Methods 0.000 claims abstract description 123
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 623
- BPLYVSYSBPLDOA-WVILEFPPSA-N N-tetracosanoylsphinganine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)CCCCCCCCCCCCCCC BPLYVSYSBPLDOA-WVILEFPPSA-N 0.000 claims description 441
- VODZWWMEJITOND-NXCSZAMKSA-N N-octadecanoylsphingosine Chemical compound CCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)\C=C\CCCCCCCCCCCCC VODZWWMEJITOND-NXCSZAMKSA-N 0.000 claims description 426
- PGROHZHFGAHXNO-PMERELPUSA-N 2-[[(2s)-2-(hexadecanoylamino)-6-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]hexanoyl]amino]ethyl 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@H](C(=O)NCCOP([O-])(=O)OCC[N+](C)(C)C)CCCCNC1=CC=C([N+]([O-])=O)C2=NON=C12 PGROHZHFGAHXNO-PMERELPUSA-N 0.000 claims description 396
- XWBWIAOWSABHFI-NUKVNZTCSA-N N-icosanoylsphingosine Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)\C=C\CCCCCCCCCCCCC XWBWIAOWSABHFI-NUKVNZTCSA-N 0.000 claims description 366
- 235000012000 cholesterol Nutrition 0.000 claims description 310
- KEPQASGDXIEOIL-UHFFFAOYSA-N (2S,3R)-N-(docosanoate)-1,3-dihydroxy-2-amino-octadeca-4-(E)-ene Natural products CCCCCCCCCCCCCCCCCCCCCC(=O)NC(CO)C(O)C=CCCCCCCCCCCCCC KEPQASGDXIEOIL-UHFFFAOYSA-N 0.000 claims description 264
- KEPQASGDXIEOIL-GLQCRSEXSA-N N-docosanoylsphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)\C=C\CCCCCCCCCCCCC KEPQASGDXIEOIL-GLQCRSEXSA-N 0.000 claims description 264
- 101710095342 Apolipoprotein B Proteins 0.000 claims description 263
- 102100040202 Apolipoprotein B-100 Human genes 0.000 claims description 263
- 108010059886 Apolipoprotein A-I Proteins 0.000 claims description 260
- 102000005666 Apolipoprotein A-I Human genes 0.000 claims description 260
- SXPRAKSDHOEHIG-ZESVVUHVSA-N N-docosanoylsphinganine Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)CCCCCCCCCCCCCCC SXPRAKSDHOEHIG-ZESVVUHVSA-N 0.000 claims description 226
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 218
- 239000000523 sample Substances 0.000 claims description 165
- 150000003626 triacylglycerols Chemical class 0.000 claims description 159
- 238000008214 LDL Cholesterol Methods 0.000 claims description 148
- 230000003247 decreasing effect Effects 0.000 claims description 137
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 claims description 128
- YDNKGFDKKRUKPY-TURZORIXSA-N N-hexadecanoylsphingosine Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)\C=C\CCCCCCCCCCCCC YDNKGFDKKRUKPY-TURZORIXSA-N 0.000 claims description 128
- 108010010234 HDL Lipoproteins Proteins 0.000 claims description 122
- 102000015779 HDL Lipoproteins Human genes 0.000 claims description 122
- 238000011282 treatment Methods 0.000 claims description 111
- SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 claims description 104
- 239000013068 control sample Substances 0.000 claims description 91
- YAMUFBLWGFFICM-PTGWMXDISA-N 1-O-oleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C YAMUFBLWGFFICM-PTGWMXDISA-N 0.000 claims description 75
- ZJVVOYPTFQEGPH-UHFFFAOYSA-N 102917-80-6 Natural products CCCCCCCCCCCCCCCCCCCCCCCC(=O)NC(CO)C(O)C=CCCCCCCCCCCCCC ZJVVOYPTFQEGPH-UHFFFAOYSA-N 0.000 claims description 73
- ZJVVOYPTFQEGPH-AUTSUKAISA-N N-tetracosanoylsphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)\C=C\CCCCCCCCCCCCC ZJVVOYPTFQEGPH-AUTSUKAISA-N 0.000 claims description 73
- SPJFYYJXNPEZDW-FTJOPAKQSA-N 1-linoleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C SPJFYYJXNPEZDW-FTJOPAKQSA-N 0.000 claims description 67
- KDEYEEYMIPNKIJ-OGIIFMLESA-N beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-N-tetracosanoylsphingosine Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KDEYEEYMIPNKIJ-OGIIFMLESA-N 0.000 claims description 60
- 206010000891 acute myocardial infarction Diseases 0.000 claims description 55
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 51
- ASWBNKHCZGQVJV-HSZRJFAPSA-N 1-hexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-HSZRJFAPSA-N 0.000 claims description 34
- 239000003814 drug Substances 0.000 claims description 27
- 108010028554 LDL Cholesterol Proteins 0.000 claims description 22
- 229940079593 drug Drugs 0.000 claims description 19
- CJROVRTUSFQVMR-GVOPMEMSSA-N N-hexacosanoylsphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)\C=C\CCCCCCCCCCCCC CJROVRTUSFQVMR-GVOPMEMSSA-N 0.000 claims description 17
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 17
- 108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 claims description 16
- 102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 claims description 16
- 108010023302 HDL Cholesterol Proteins 0.000 claims description 16
- 230000008859 change Effects 0.000 claims description 16
- 238000004949 mass spectrometry Methods 0.000 claims description 16
- 210000002966 serum Anatomy 0.000 claims description 14
- 230000009469 supplementation Effects 0.000 claims description 12
- 201000001320 Atherosclerosis Diseases 0.000 claims description 11
- FJLGEFLZQAZZCD-MCBHFWOFSA-N (3R,5S)-fluvastatin Chemical compound C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 FJLGEFLZQAZZCD-MCBHFWOFSA-N 0.000 claims description 10
- 229960003765 fluvastatin Drugs 0.000 claims description 10
- 108010056301 Apolipoprotein C-III Proteins 0.000 claims description 9
- 102000030169 Apolipoprotein C-III Human genes 0.000 claims description 9
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 claims description 8
- 210000004369 blood Anatomy 0.000 claims description 8
- 239000008280 blood Substances 0.000 claims description 8
- 229940125753 fibrate Drugs 0.000 claims description 8
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 7
- 229920000080 bile acid sequestrant Polymers 0.000 claims description 7
- 230000027455 binding Effects 0.000 claims description 7
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 7
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 7
- 238000000926 separation method Methods 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 5
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 5
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 5
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 5
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 5
- 229960005370 atorvastatin Drugs 0.000 claims description 5
- 229960005110 cerivastatin Drugs 0.000 claims description 5
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 claims description 5
- 235000015872 dietary supplement Nutrition 0.000 claims description 5
- 238000003018 immunoassay Methods 0.000 claims description 5
- 229960004844 lovastatin Drugs 0.000 claims description 5
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 5
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 5
- 229960002797 pitavastatin Drugs 0.000 claims description 5
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 claims description 5
- 229960002965 pravastatin Drugs 0.000 claims description 5
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 5
- 229960000672 rosuvastatin Drugs 0.000 claims description 5
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 5
- 229960002855 simvastatin Drugs 0.000 claims description 5
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 5
- 238000004704 ultra performance liquid chromatography Methods 0.000 claims description 5
- 108010024284 Apolipoprotein C-II Proteins 0.000 claims description 3
- 102100039998 Apolipoprotein C-II Human genes 0.000 claims description 3
- 238000002965 ELISA Methods 0.000 claims description 3
- 238000005481 NMR spectroscopy Methods 0.000 claims description 3
- 238000010387 dual polarisation interferometry Methods 0.000 claims description 3
- 238000001506 fluorescence spectroscopy Methods 0.000 claims description 3
- 208000030613 peripheral artery disease Diseases 0.000 claims description 3
- 208000023516 stroke disease Diseases 0.000 claims description 3
- VTAKZNRDSPNOAU-UHFFFAOYSA-M 2-(chloromethyl)oxirane;hydron;prop-2-en-1-amine;n-prop-2-enyldecan-1-amine;trimethyl-[6-(prop-2-enylamino)hexyl]azanium;dichloride Chemical group Cl.[Cl-].NCC=C.ClCC1CO1.CCCCCCCCCCNCC=C.C[N+](C)(C)CCCCCCNCC=C VTAKZNRDSPNOAU-UHFFFAOYSA-M 0.000 claims description 2
- YZQLWPMZQVHJED-UHFFFAOYSA-N 2-methylpropanethioic acid S-[2-[[[1-(2-ethylbutyl)cyclohexyl]-oxomethyl]amino]phenyl] ester Chemical compound C=1C=CC=C(SC(=O)C(C)C)C=1NC(=O)C1(CC(CC)CC)CCCCC1 YZQLWPMZQVHJED-UHFFFAOYSA-N 0.000 claims description 2
- 229920001268 Cholestyramine Polymers 0.000 claims description 2
- 229920002905 Colesevelam Polymers 0.000 claims description 2
- 229920002911 Colestipol Polymers 0.000 claims description 2
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 claims description 2
- MZZLGJHLQGUVPN-HAWMADMCSA-N anacetrapib Chemical compound COC1=CC(F)=C(C(C)C)C=C1C1=CC=C(C(F)(F)F)C=C1CN1C(=O)O[C@H](C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)[C@@H]1C MZZLGJHLQGUVPN-HAWMADMCSA-N 0.000 claims description 2
- 229950000285 anacetrapib Drugs 0.000 claims description 2
- 229960000516 bezafibrate Drugs 0.000 claims description 2
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 229960001214 clofibrate Drugs 0.000 claims description 2
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 claims description 2
- 229960001152 colesevelam Drugs 0.000 claims description 2
- 229960002604 colestipol Drugs 0.000 claims description 2
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 claims description 2
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 claims description 2
- 229960000815 ezetimibe Drugs 0.000 claims description 2
- 229960002297 fenofibrate Drugs 0.000 claims description 2
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 claims description 2
- 229960003627 gemfibrozil Drugs 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- IMNTVVOUWFPRSB-JWQCQUIFSA-N sch-48461 Chemical compound C1=CC(OC)=CC=C1[C@H]1N(C=2C=CC(OC)=CC=2)C(=O)[C@@H]1CCCC1=CC=CC=C1 IMNTVVOUWFPRSB-JWQCQUIFSA-N 0.000 claims description 2
- CMSGWTNRGKRWGS-NQIIRXRSSA-N torcetrapib Chemical group COC(=O)N([C@H]1C[C@@H](CC)N(C2=CC=C(C=C21)C(F)(F)F)C(=O)OCC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CMSGWTNRGKRWGS-NQIIRXRSSA-N 0.000 claims description 2
- 229950004514 torcetrapib Drugs 0.000 claims description 2
- 239000012472 biological sample Substances 0.000 abstract description 9
- 238000003745 diagnosis Methods 0.000 abstract description 3
- 208000037998 chronic venous disease Diseases 0.000 abstract 5
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 409
- 150000008106 phosphatidylserines Chemical class 0.000 description 255
- FGJIXPPBZNPEHW-CRMMDXJYSA-N beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-N-eicosanoylsphingosine Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 FGJIXPPBZNPEHW-CRMMDXJYSA-N 0.000 description 218
- FYMCIBHUFSIWCE-WVXFKAQASA-N cholesteryl linolenate Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCCCCCC\C=C/C\C=C/C\C=C/CC)C1 FYMCIBHUFSIWCE-WVXFKAQASA-N 0.000 description 167
- QYWVASPEUXEHSY-NNRNTGNWSA-N beta-D-galactosyl-(1->4)-beta-D-glucosyl-N-(docosanoyl)sphingosine Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 QYWVASPEUXEHSY-NNRNTGNWSA-N 0.000 description 98
- RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 description 79
- VOZHMDQUIRUFQW-LOTHNZFDSA-N beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-N-octadecanoylsphingosine Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 VOZHMDQUIRUFQW-LOTHNZFDSA-N 0.000 description 75
- HODJWNWCVNUPAQ-XDOSKZMUSA-N cholesteryl palmitoleate Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCCCCCC\C=C/CCCCCC)C1 HODJWNWCVNUPAQ-XDOSKZMUSA-N 0.000 description 72
- YEYCQJVCAMFWCO-PXBBAZSNSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] formate Chemical compound C1C=C2C[C@@H](OC=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 YEYCQJVCAMFWCO-PXBBAZSNSA-N 0.000 description 66
- 150000002305 glucosylceramides Chemical class 0.000 description 62
- 150000001982 diacylglycerols Chemical class 0.000 description 53
- MKOKWBRPIBQYJJ-WZBOJYASSA-N beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-N-[(15Z)-tetracosenoyl]sphingosine Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@@H]([C@H](O)/C=C/CCCCCCCCCCCCC)NC(=O)CCCCCCCCCCCCC\C=C/CCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MKOKWBRPIBQYJJ-WZBOJYASSA-N 0.000 description 46
- 101150102415 Apob gene Proteins 0.000 description 41
- RLMIGWIAENJHMP-RJRTUNKTSA-N cholesteryl (9Z)-heptadecenoate Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCCCCCC\C=C/CCCCCCC)C1 RLMIGWIAENJHMP-RJRTUNKTSA-N 0.000 description 26
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 21
- XWKBYMQTSGGZLW-PHSKOSPPSA-N PKDdiA-PC Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC(=O)\C=C\C(O)=O XWKBYMQTSGGZLW-PHSKOSPPSA-N 0.000 description 18
- QEDPUVGSSDPBMD-XTAIVQBESA-N N-lignoceroylsphingosine-1-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)[C@H](O)\C=C\CCCCCCCCCCCCC QEDPUVGSSDPBMD-XTAIVQBESA-N 0.000 description 15
- KYICBZWZQPCUMO-PSALXKTOSA-N N-myristoylsphingosine-1-phosphocholine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@H](COP([O-])(=O)OCC[N+](C)(C)C)NC(=O)CCCCCCCCCCCCC KYICBZWZQPCUMO-PSALXKTOSA-N 0.000 description 15
- DFELABABMXOKTD-IYFIADHGSA-N beta-D-glucosyl-N-eicosanoylsphingosine Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)N[C@H]([C@H](O)\C=C\CCCCCCCCCCCCC)CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O DFELABABMXOKTD-IYFIADHGSA-N 0.000 description 15
- XZFUGMCJZFRBKF-BDJFIEMMSA-N cholesteryl (5Z,8Z,11Z,14Z,17Z-eicosapentaenoate) Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC)C1 XZFUGMCJZFRBKF-BDJFIEMMSA-N 0.000 description 15
- 230000000875 corresponding effect Effects 0.000 description 13
- HLIJNIKSBCIDGO-QKLMXXKVSA-N beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-N-hexadecanoylsphingosine Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HLIJNIKSBCIDGO-QKLMXXKVSA-N 0.000 description 12
- -1 C18:3 Cholesterol ester Chemical class 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- NAACPBBQTFFYQB-LJAITQKLSA-N cholesteryl linoleate Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCCCCCC\C=C/C\C=C/CCCCC)C1 NAACPBBQTFFYQB-LJAITQKLSA-N 0.000 description 11
- 238000005259 measurement Methods 0.000 description 10
- 241000894007 species Species 0.000 description 10
- SXZWBNWTCVLZJN-NMIJJABPSA-N N-tricosanoylsphing-4-enine-1-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)[C@H](O)\C=C\CCCCCCCCCCCCC SXZWBNWTCVLZJN-NMIJJABPSA-N 0.000 description 9
- 239000003550 marker Substances 0.000 description 9
- 239000002245 particle Substances 0.000 description 8
- 238000011002 quantification Methods 0.000 description 7
- 108010007622 LDL Lipoproteins Proteins 0.000 description 6
- 102000007330 LDL Lipoproteins Human genes 0.000 description 6
- YMQZQHIESOAPQH-JXGHDCMNSA-N N-heptadecanoylsphingosine-1-phosphocholine Chemical compound CCCCCCCCCCCCCCCCC(=O)N[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)[C@H](O)\C=C\CCCCCCCCCCCCC YMQZQHIESOAPQH-JXGHDCMNSA-N 0.000 description 6
- YMYQEDCYNANIPI-DYJXBSQNSA-N beta-D-glucosyl-N-octadecanoylsphingosine Chemical compound CCCCCCCCCCCCCCCCCC(=O)N[C@H]([C@H](O)\C=C\CCCCCCCCCCCCC)CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O YMYQEDCYNANIPI-DYJXBSQNSA-N 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 208000010125 myocardial infarction Diseases 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 5
- 239000012491 analyte Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 108010087614 Apolipoprotein A-II Proteins 0.000 description 3
- 102000009081 Apolipoprotein A-II Human genes 0.000 description 3
- 101710105047 Lipoprotein B Proteins 0.000 description 3
- 102000004895 Lipoproteins Human genes 0.000 description 3
- 108090001030 Lipoproteins Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- LKQLRGMMMAHREN-YJFXYUILSA-N N-stearoylsphingosine-1-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)N[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)[C@H](O)\C=C\CCCCCCCCCCCCC LKQLRGMMMAHREN-YJFXYUILSA-N 0.000 description 3
- POQRWMRXUOPCLD-GZXCKHLVSA-N beta-D-glucosyl-N-(tetracosanoyl)sphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@H]([C@H](O)\C=C\CCCCCCCCCCCCC)CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O POQRWMRXUOPCLD-GZXCKHLVSA-N 0.000 description 3
- 230000007211 cardiovascular event Effects 0.000 description 3
- RJECHNNFRHZQKU-RMUVNZEASA-N cholesteryl oleate Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)C1 RJECHNNFRHZQKU-RMUVNZEASA-N 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- 102100037320 Apolipoprotein A-IV Human genes 0.000 description 2
- 101710086822 Apolipoprotein C-IV Proteins 0.000 description 2
- 102100037322 Apolipoprotein C-IV Human genes 0.000 description 2
- 102100037324 Apolipoprotein M Human genes 0.000 description 2
- 101710095646 Apolipoprotein M Proteins 0.000 description 2
- 102000013918 Apolipoproteins E Human genes 0.000 description 2
- 108010025628 Apolipoproteins E Proteins 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010053172 Fatal outcomes Diseases 0.000 description 2
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 102100035476 Serum paraoxonase/arylesterase 1 Human genes 0.000 description 2
- 101710180981 Serum paraoxonase/arylesterase 1 Proteins 0.000 description 2
- 108020004459 Small interfering RNA Proteins 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 108010073614 apolipoprotein A-IV Proteins 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- 231100001261 hazardous Toxicity 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 238000012615 high-resolution technique Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002552 multiple reaction monitoring Methods 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000012502 risk assessment Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000004055 small Interfering RNA Substances 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 description 2
- 238000001195 ultra high performance liquid chromatography Methods 0.000 description 2
- IHNKQIMGVNPMTC-UHFFFAOYSA-N (2-hydroxy-3-octadecanoyloxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C IHNKQIMGVNPMTC-UHFFFAOYSA-N 0.000 description 1
- HVYWMOMLDIMFJA-UHFFFAOYSA-N 3-cholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 HVYWMOMLDIMFJA-UHFFFAOYSA-N 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 102100029470 Apolipoprotein E Human genes 0.000 description 1
- 101710095339 Apolipoprotein E Proteins 0.000 description 1
- 102000007592 Apolipoproteins Human genes 0.000 description 1
- 108010071619 Apolipoproteins Proteins 0.000 description 1
- 102000018623 Apolipoproteins M Human genes 0.000 description 1
- 108010027018 Apolipoproteins M Proteins 0.000 description 1
- 102000006996 Aryldialkylphosphatase Human genes 0.000 description 1
- 108010008184 Aryldialkylphosphatase Proteins 0.000 description 1
- 102000004954 Biglycan Human genes 0.000 description 1
- 108090001138 Biglycan Proteins 0.000 description 1
- 102000003780 Clusterin Human genes 0.000 description 1
- 108090000197 Clusterin Proteins 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 101710091951 Glycerol-3-phosphate acyltransferase Proteins 0.000 description 1
- 102100027772 Haptoglobin-related protein Human genes 0.000 description 1
- 101710122541 Haptoglobin-related protein Proteins 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 102000017286 Histone H2A Human genes 0.000 description 1
- 108050005231 Histone H2A Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 102000011971 Sphingomyelin Phosphodiesterase Human genes 0.000 description 1
- 108010061312 Sphingomyelin Phosphodiesterase Proteins 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 108010031318 Vitronectin Proteins 0.000 description 1
- 102100035140 Vitronectin Human genes 0.000 description 1
- JLPULHDHAOZNQI-JLOPVYAASA-N [(2r)-3-hexadecanoyloxy-2-[(9e,12e)-octadeca-9,12-dienoyl]oxypropyl] 2-(trimethylazaniumyl)ethyl phosphate Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC JLPULHDHAOZNQI-JLOPVYAASA-N 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 239000000091 biomarker candidate Substances 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 208000006170 carotid stenosis Diseases 0.000 description 1
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 description 1
- 239000012568 clinical material Substances 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 150000002433 hydrophilic molecules Chemical class 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000005040 ion trap Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000002705 metabolomic analysis Methods 0.000 description 1
- 230000001431 metabolomic effect Effects 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000001269 time-of-flight mass spectrometry Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/92—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving lipids, e.g. cholesterol, lipoproteins, or their receptors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2405/00—Assays, e.g. immunoassays or enzyme assays, involving lipids
- G01N2405/04—Phospholipids, i.e. phosphoglycerides
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2405/00—Assays, e.g. immunoassays or enzyme assays, involving lipids
- G01N2405/04—Phospholipids, i.e. phosphoglycerides
- G01N2405/06—Glycophospholipids, e.g. phosphatidyl inositol
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2570/00—Omics, e.g. proteomics, glycomics or lipidomics; Methods of analysis focusing on the entire complement of classes of biological molecules or subsets thereof, i.e. focusing on proteomes, glycomes or lipidomes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/32—Cardiovascular disorders
- G01N2800/324—Coronary artery diseases, e.g. angina pectoris, myocardial infarction
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/50—Determining the risk of developing a disease
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10006399 | 2010-06-20 | ||
| EP10006399.9 | 2010-06-20 | ||
| US35667510P | 2010-06-21 | 2010-06-21 | |
| US61/356,675 | 2010-06-21 | ||
| PCT/EP2011/060253 WO2011161062A2 (en) | 2010-06-20 | 2011-06-20 | Lipidomic biomarkers for identification of high-risk coronary artery disease patients |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2801459A1 CA2801459A1 (en) | 2011-12-29 |
| CA2801459C true CA2801459C (en) | 2018-04-24 |
Family
ID=44627661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2801459A Active CA2801459C (en) | 2010-06-20 | 2011-06-20 | Lipidomic biomarkers for identification of high-risk coronary artery disease patients |
Country Status (6)
| Country | Link |
|---|---|
| US (5) | US9201080B2 (cg-RX-API-DMAC7.html) |
| EP (2) | EP2583107A2 (cg-RX-API-DMAC7.html) |
| JP (2) | JP6262529B2 (cg-RX-API-DMAC7.html) |
| CN (2) | CN103154742B (cg-RX-API-DMAC7.html) |
| CA (1) | CA2801459C (cg-RX-API-DMAC7.html) |
| WO (1) | WO2011161062A2 (cg-RX-API-DMAC7.html) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9541565B2 (en) | 2011-04-08 | 2017-01-10 | Zora Biosciences Oy | Biomarkers for sensitive detection of statin-induced muscle toxicity |
| EP2592423A1 (en) | 2011-11-08 | 2013-05-15 | Zora Biosciences OY | Lipidomic biomarkers for the prediction of cardiovascular outcomes in coronary artery disease patients not undergoing statin treatment |
| EP2592422A1 (en) * | 2011-11-08 | 2013-05-15 | Zora Biosciences OY | Lipidomic biomarkers for the prediction of cardiovascular outcomes in coronary artery disease patients undergoing statin treatment |
| ES2552371T3 (es) * | 2012-05-25 | 2015-11-27 | Zora Biosciences Oy | Biomarcadores sensibles, eficaces e inocuos, para la inhibición de la Proproteína Convertasa Subtilisina/Kexina de tipo 9 (PCSK9) |
| US20130312498A1 (en) * | 2012-05-25 | 2013-11-28 | Foundation For Health Improvement And Technology | Cardiovascular disease risk assessment and treatment by sterol and/or stanol markers |
| WO2014135696A1 (en) * | 2013-03-08 | 2014-09-12 | Zora Biosciences Oy | Non-high density lipoprotein derived cvd markers |
| CN104063570B (zh) * | 2013-03-20 | 2017-06-16 | 中国科学院大连化学物理研究所 | 一种脂质代谢网络动态研究的方法 |
| KR101594515B1 (ko) * | 2013-12-24 | 2016-02-16 | 연세대학교 산학협력단 | 혈장 대사체를 이용한 제2형 당뇨병 진단 키트 |
| NZ724790A (en) | 2014-04-10 | 2022-07-29 | MEP Equine Solutions LLC | Method for the quantification of parasite eggs in feces |
| US9347960B2 (en) * | 2014-06-16 | 2016-05-24 | Zora Biosciences, Oy | Ceramides and their use in diagnosing CVD |
| CN108027354B (zh) * | 2015-08-20 | 2021-01-08 | 深圳华大生命科学研究院 | 冠心病的生物标志物 |
| WO2017097852A2 (en) | 2015-12-07 | 2017-06-15 | Zora Biosciences Oy | Use of ceramides and lpls in diagnosing cvd |
| CN105424841B (zh) * | 2015-12-25 | 2017-11-03 | 齐炼文 | 用于诊断冠状动脉粥样硬化的代谢标志物 |
| CN105486773A (zh) * | 2015-12-25 | 2016-04-13 | 齐炼文 | 用于诊断冠心病的代谢标志物 |
| CN105628809B (zh) * | 2015-12-25 | 2018-04-03 | 中国药科大学 | 用于诊断区分冠状动脉粥样硬化和冠心病的代谢标志物 |
| CN105445408B (zh) * | 2016-01-25 | 2018-06-12 | 齐炼文 | 诊断区分冠状动脉粥样硬化和稳定型心绞痛的代谢标志物 |
| CN109870536B (zh) * | 2017-12-05 | 2021-08-10 | 中国科学院大连化学物理研究所 | 一种基于液相色谱-质谱联用的高覆盖脂质组学分析方法 |
| CN114062581A (zh) * | 2017-12-14 | 2022-02-18 | 江苏豪思生物科技有限公司 | 一种用于评估冠状动脉疾病的试剂盒 |
| EP3891509A1 (en) | 2018-12-06 | 2021-10-13 | Zora Biosciences OY | Biomarkers for cardiovascular events |
| US20240003921A1 (en) * | 2020-10-16 | 2024-01-04 | Indian Institute Of Science | A lipid based indicator for cardiovascular disorder |
| CN112305124B (zh) * | 2020-10-30 | 2022-03-04 | 河北医科大学第二医院 | 一种生物标志物及其在疾病诊断中的应用 |
| CN112147344B (zh) * | 2020-10-30 | 2021-07-13 | 河北医科大学第二医院 | 动脉粥样硬化性脑梗死的代谢标志物及其在诊疗中的应用 |
| CN112305119B (zh) * | 2020-10-30 | 2021-08-17 | 河北医科大学第二医院 | 动脉粥样硬化性脑梗死的生物标志物及其应用 |
| EP4043884A1 (en) * | 2021-02-10 | 2022-08-17 | Eberhard-Karls-Universität Tübingen | Medium-chain fatty acyls and phospholipids as biomarkers for cardiovascular diseases |
| CN113533754A (zh) * | 2021-07-12 | 2021-10-22 | 北京市心肺血管疾病研究所 | 神经酰胺在制备用于评估高血压患者发生不良事件风险的试剂盒中的应用 |
| CN114791459B (zh) * | 2022-03-29 | 2023-02-14 | 浙江苏可安药业有限公司 | 用于检测肺结核的血清代谢标志物及其试剂盒 |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002514999A (ja) * | 1991-09-26 | 2002-05-21 | ヘム・ファーマスーティカル・コーポレーション | dsRNAを用いてIL−1を中和する方法 |
| ATE489633T1 (de) | 1997-06-10 | 2010-12-15 | Lpath Inc | Verfahren zum frühzeitigen nachweis herzerkrankungen |
| AU5610801A (en) * | 2000-03-03 | 2001-09-12 | Gerd Schmitz | Method for the analysis of exogenic and endogenic cell activation based on measuring the aggregation of receptors |
| US6664230B1 (en) * | 2000-08-24 | 2003-12-16 | The Regents Of The University Of California | Orally administered peptides to ameliorate atherosclerosis |
| JP4062514B2 (ja) | 2001-01-02 | 2008-03-19 | ザ・クリーブランド・クリニック・ファンデーション | ミエロペルオキシダーゼ、心臓血管疾患についての危険性指示因子 |
| ES2429528T3 (es) | 2001-01-02 | 2013-11-15 | The Cleveland Clinic Foundation | Mieloperoxidasa, un indicador de riesgo para enfermedad cardiovascular |
| BR0206400A (pt) | 2001-01-10 | 2005-01-18 | Univ Michigan | Compostos de amino ceramidas e seus usos em métodos terapêuticos |
| DE60225145D1 (de) | 2001-07-06 | 2008-04-03 | Lipomics Technologies Inc | Erzeugen, betrachten, interpretieren und verwenden einer quantitativen datenbank von metaboliten |
| WO2003017177A2 (en) * | 2001-08-13 | 2003-02-27 | Beyong Genomics, Inc. | Method and system for profiling biological systems |
| US7262017B2 (en) * | 2001-09-14 | 2007-08-28 | Torrey Pines Institute For Molecular Studies | Diagnostic markers for ischemia |
| WO2004038381A2 (en) | 2002-10-25 | 2004-05-06 | Metabolon, Inc. | Methods for drug discovery, disease treatment, and diagnosis using metabolomics |
| EP1431399A1 (en) * | 2002-12-20 | 2004-06-23 | Clinigenetics | Methods and composition for identifying therapeutic agents of atherosclerotic plaque lesions |
| WO2004085610A2 (en) * | 2003-03-28 | 2004-10-07 | Washington University In St. Louis | Multidimensional mass spectrometry of serum and cellular lipids directly from biologic extracts |
| AU2004308966A1 (en) * | 2003-12-23 | 2005-07-14 | Musc Foundaton For Research Development | Methods and compositions for the prevention and treatment of inflammatory diseases or conditions |
| CN1897961A (zh) * | 2003-12-23 | 2007-01-17 | Musc研究发展基金会 | 预防和治疗炎性疾病或病症的方法和组合物 |
| US20080027088A1 (en) | 2004-03-26 | 2008-01-31 | Warner-Lambert Company, Llc | Imidazole-Based Hmg-Coa Reductase Inhibitors |
| FI20041340A0 (fi) | 2004-10-15 | 2004-10-15 | Jurilab Ltd Oy | Menetelmä ja testipakkaus äkillisen sydäninfarktin riskin havaitsemiseksi |
| JP2008531603A (ja) | 2005-03-03 | 2008-08-14 | バイタル ヘルス サイエンシズ プロプライアタリー リミティド | 脂質低下特性を有する化合物 |
| EP1726962A1 (en) | 2005-05-24 | 2006-11-29 | Leiden University Medical Center | Apolipoprotein E plasma levels for monitoring and reducing the risk of cardiovascular disease |
| WO2007050318A2 (en) * | 2005-10-24 | 2007-05-03 | Duke University | Lipidomics approaches for central nervous system disorders |
| US7972802B2 (en) | 2005-10-31 | 2011-07-05 | University Of Washington | Lipoprotein-associated markers for cardiovascular disease |
| WO2007127192A2 (en) | 2006-04-24 | 2007-11-08 | Duke University | Lipidomic approaches to determining drug response phenotypes in cardiovascular disease |
| US8137977B2 (en) * | 2006-04-24 | 2012-03-20 | Children's Hospital & Research Center At Oakland | Lipidomic approaches to determining drug response phenotypes in cardiovascular disease |
| CN101522910A (zh) | 2006-06-12 | 2009-09-02 | 佐拉生物科学有限公司 | 肌病的诊断方法 |
| JP2009540314A (ja) * | 2006-06-12 | 2009-11-19 | ゾラ バイオサイエンシズ オイ | 筋障害診断方法 |
| DE102006034153B4 (de) | 2006-07-24 | 2018-02-08 | Magna powertrain gmbh & co kg | Getriebe |
| US8321154B2 (en) | 2007-03-26 | 2012-11-27 | Bg Medicine, Inc. | Methods for detecting coronary artery disease |
| EP2153236A1 (en) | 2007-06-07 | 2010-02-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method for assessing the risk of a cardiovascular disease and for diagnosing dyslipidemia |
| US7847245B2 (en) * | 2007-07-18 | 2010-12-07 | Platomics, Inc. | Multiplexing matrix-analyte stereo electronic interactions for high throughput shotgun metabolomics |
| US8026099B2 (en) | 2007-07-26 | 2011-09-27 | Washington University | Lipid profile as a biomarker for early detection of neurological disorders |
| WO2009132082A2 (en) | 2008-04-22 | 2009-10-29 | Medical College Of Georgia Research Institute, Inc. | Immunogenic compositions containing ceramide and methods of use thereof |
| JP2010038858A (ja) * | 2008-08-08 | 2010-02-18 | Ikagaku:Kk | 動脈硬化に起因する疾患の発症を予知するために用いるキット |
| WO2010038104A1 (en) * | 2008-10-03 | 2010-04-08 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Combination of cardiovascular risk factors for the diagnosis/prognosis of a cardiovascular disease/event. |
| WO2011063470A1 (en) | 2009-11-27 | 2011-06-03 | Baker Idi Heart And Diabetes Institute Holdings Limited | Lipid biomarkers for stable and unstable heart disease |
| NO2385374T3 (cg-RX-API-DMAC7.html) | 2010-05-05 | 2014-06-07 |
-
2011
- 2011-06-20 EP EP11728229.3A patent/EP2583107A2/en not_active Withdrawn
- 2011-06-20 CA CA2801459A patent/CA2801459C/en active Active
- 2011-06-20 CN CN201180035877.9A patent/CN103154742B/zh active Active
- 2011-06-20 WO PCT/EP2011/060253 patent/WO2011161062A2/en not_active Ceased
- 2011-06-20 CN CN201711362402.6A patent/CN108445241B/zh active Active
- 2011-06-20 EP EP17184534.0A patent/EP3293522A3/en not_active Withdrawn
- 2011-06-20 JP JP2013515841A patent/JP6262529B2/ja active Active
- 2011-06-20 US US13/805,319 patent/US9201080B2/en active Active
-
2015
- 2015-10-05 US US14/875,087 patent/US9841431B2/en active Active
-
2017
- 2017-03-07 JP JP2017042837A patent/JP6605521B2/ja active Active
- 2017-11-03 US US15/803,252 patent/US10261101B2/en active Active
-
2019
- 2019-03-04 US US16/291,845 patent/US10955427B2/en active Active
-
2021
- 2021-02-17 US US17/177,503 patent/US12270816B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US10955427B2 (en) | 2021-03-23 |
| EP2583107A2 (en) | 2013-04-24 |
| US12270816B2 (en) | 2025-04-08 |
| US20160025751A1 (en) | 2016-01-28 |
| US9841431B2 (en) | 2017-12-12 |
| US9201080B2 (en) | 2015-12-01 |
| EP3293522A3 (en) | 2018-05-02 |
| CN108445241A (zh) | 2018-08-24 |
| JP6605521B2 (ja) | 2019-11-13 |
| US20130216560A1 (en) | 2013-08-22 |
| CA2801459A1 (en) | 2011-12-29 |
| WO2011161062A2 (en) | 2011-12-29 |
| CN103154742B (zh) | 2017-11-21 |
| US10261101B2 (en) | 2019-04-16 |
| JP2017129592A (ja) | 2017-07-27 |
| JP2013531238A (ja) | 2013-08-01 |
| EP3293522A2 (en) | 2018-03-14 |
| US20180067138A1 (en) | 2018-03-08 |
| CN108445241B (zh) | 2021-11-02 |
| US20210239719A1 (en) | 2021-08-05 |
| JP6262529B2 (ja) | 2018-01-17 |
| CN103154742A (zh) | 2013-06-12 |
| US20200003794A1 (en) | 2020-01-02 |
| WO2011161062A3 (en) | 2012-06-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US12270816B2 (en) | Lipidomic biomarkers for identification of high-risk coronary artery disease patients | |
| US20240385201A1 (en) | Lipidomic biomarkers for atherosclerosis and cardiovascular disease | |
| US9459265B2 (en) | Lipidomic biomarkers for the prediction of cardiovascular outcomes in coronary artery disease patients undergoing statin treatment | |
| US9863965B2 (en) | Lipidomic biomarkers for the prediction of cardiovascular outcomes in coronary artery disease patients not undergoing statin treatment |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20131220 |