CN104356209A - Polypeptide for reducing blood pressure and protecting heart - Google Patents
Polypeptide for reducing blood pressure and protecting heart Download PDFInfo
- Publication number
- CN104356209A CN104356209A CN201410449896.1A CN201410449896A CN104356209A CN 104356209 A CN104356209 A CN 104356209A CN 201410449896 A CN201410449896 A CN 201410449896A CN 104356209 A CN104356209 A CN 104356209A
- Authority
- CN
- China
- Prior art keywords
- polypeptide
- blood pressure
- hypertension
- heart
- seq
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
The invention relates to polypeptide for reducing blood pressure and protecting the heart. The sequence of polypeptide is as shown in SEQ ID NO: 1-2. Polypeptide has a relatively good effect of treating hypertension and also has the effect of protecting the heart.
Description
Invention field
The invention belongs to Biotechnological medicine and biomedicine field, be specifically related to a kind of reducing blood pressure and the polypeptide of cardioprotection, and this polypeptide is in treatment essential hypertension and prevent in heart disease etc. effect.
Background of invention
Hypertension is the worldwide problem of serious harm human health, and Chinese Prevalence of Hypertension 18.8% (2002), there are nearly 200,000,000 hyperpietics in the current whole nation.Hypertension is the Major Risk Factors of cardiovascular and cerebrovascular disease, Chinese Cerebral Haemorrhage Invasion Rate about 2,50/,100,000 people, Incidence of CHD about 50,/10 ten thousand people, actively controls the important measures that hypertension is preventing brain stroke and coronary heart disease.Current Chinese outpatient service hyperpietic treats inverse amplification factor 30.6%, and Chinese hypertension therapeutic overall control rate only 6.1%.
Treatment and preventing hypertension are the very important problems of current social.Peptide is the important Altace Ramipril of a class, and the newfound active polypeptide relevant to hypertension mainly contains following several:
(1) Apelin cardiovascular active polypeptide
Apelin is the new active polypeptide that Japanese scholars Tatemoto etc. utilizes " orphan receptor strategy " to extract from ox gastric secretions first in 1998 by reverse pharmacology method, is the endogenic ligand of G-protein coupling receptor APJ.Apelin participates in the adjustment of different physiological roles and pathologic process, especially at many-sided the important regulative such as blood pressure regulation, cardiovascular function, central nervous system function.In recent years, Apelin has been proved the adjustment that take part in blood pressure, and Apelin not only can change arterial pressure, can also play the vasorelaxation action of endothelium-dependent relaxation and the positive inotropic action to isolated heart in vivo.Apelin, as a kind of diuresis neuropeptide, by the biological action suppressing the release of arginine vasopressin (argininevasopressin, AVP) neuronic activity and AVP to suppress AVP, thus regulates blood pressure and maintains body fluid equilibrium.In addition, it also causes vasodilation by NO/L-arginine pathway, shows the mechanisms mediate of the endothelium-dependent relaxation vasodilation of apelin.Apelin-Angiotensin sample acceptor-1 (AGTRL1) system has vital role for fluid homeostasis and blood pressure regulation.At present, the research strategy applying extensive family finds that Apelin with AGTRL1 gene pleiomorphism is relevant with hypertension or Relevant phenotype first on gene level, infer and be positioned at the SNPs of promoter region and haplotype variation may cause producing new transcription regulaton factor binding domain, thus affect transcribing of gene, then affect the expression of albumen.Conversely, the change of protein expression level can affect again the change of hypertensive Development process and phenotype.The severity extent of Apelin change level and essential hypertension is closely related, may have important clinical meaning for the generation of prediction primary hypertension patient adverse events and change of illness state, for predicting from now on, office hypertension and essential hypertension high risk population carry out early screening and provide new approaches.
(2) ADM2
ADM2 is calcitonin-gene-related peptide (CGRP) superfamily member of cloning recently out, and its similar, in CGRP, adrenomedullin, is worked by Calcitonin receptor-like receptor/receptor radiopharmaceuticals.IMD/ADM2 is a kind of endogenous heart-protection renal factor; in Various Tissues, play extensive biological function as circulating hormone and side/autocrine factor, have and reduce blood pressure, coronary artery dilating, anti-heart ischemia/reperfusion injury, regulate fluid and electrolyte balance, regulate the biological effect such as pituitary hormone secretion.There is reported literature, after the brain stem nucleus tractus solitaril (NTS) of CRLR expressed in abundance gives IMD Micro-perfusion in Graft After, arteriotony and heart rate can be caused obviously to rise.Due to the termination position that NTS is the peripheral organ's pressure receptor afferent fibre comprising cardiovascular systems, it is the primary central of afferent message, the endogenous IMD of prompting NTS regulates systemic hemodynamic to need can significantly reduce mouse blood pressure by autonomic nervous system competence exertion effect IMD, and it is strong to act on comparatively AMD; Can in dose-dependently making mean arterial pressure reduce; Rat total peripheral resistance can be reduced, reduce blood pressure, the capacity vessel of diastole rat.In addition, IMD, as a kind of potent vasoactive expanding peptide, has protective effect to organ.IMD has abundant expression at kidney, and infer that IMD regulates peptide as a kind of endogenous, its minimizing may play an important role in the development of hyperpietic's injury of the kidney.
(3) urotensin II (urotensinII, UII) urotensin II recently found be so far known to the strongest vaso-excitor material, it is a kind of Somatostatin cyclic peptide separated at teleostean spinal cord caudal neurosecretory system the earliest, Ames finds a kind of isolated g protein coupled receptor GPR14 first in human body, research shows that it is the specific receptors of UII, is mainly present in cardiovascular systems.Various biological effect is caused after UII and receptors bind.The UII found in human body in recent years and acceptor thereof become the focus of medical circle research, its principal biological effect is mediate vascular contraction, myocardial ischemia, short vascular smooth muscle cell and Proliferation of Cardiac Fibroblasts, short cardiac myocyte hypertrophy etc., the consequently reconstruct of heart and blood vessel.Recently, studies have found that UII can also promote that blood vessel adventitia fibroblast is to myofibroblast Phenotype Transition, promote collage synthesis, promote Adventitial fibroblasts migration.Separately studies have reported that Plasma of Patients with Hypertension UII level is apparently higher than blood pressure normal population; Carotid plaques and interior, media thickness thereof, systolic pressure etc., hypertension group is also apparently higher than normal group, and UII to the effect of Mottling formation far above other Hazard Factor such as known age, blood pressure, blood fat, showing that blood plasma UII level increases the evolution that may participate in the chronic AS of primary hypertension patient as independent hazard factor, is also important factor in essential hypertension vascular remodeling process.Nearest discovery; the rising of blood plasma UII level often occurs in endothelial function disturbance diseases, such as hypertension, diabetes, atherosclerosis; UII expresses Vcam1 and intercellular adhesion molecule-1 by stimulating endothelial cell; raise acyltransferase A and accelerate foam wanshing; active oxygen (ROS) is produced by induction, and the propagation of the synergy stimulated vascular smooth muscle cell of Ox LDL and thrombotonin.The rising of blood plasma UII level and the severity of hyperpietic's carotid atherosclerosis are proportionate.
(4) catechol chalone (catestatin) catechol chalone (catestatin) is the endogenous polypeptide of 21 amino acid compositions, derives from the chromogranin A in adrenal pheochromocytoma and adrenal neurons endochylema.The release of effective suppression sympathicoadrenal system catecholamine stimulates histamine release of mast cell, vasodilation, reduces blood pressure, reduces myocardial contraction.Primary and secondary hypertension patients blood plasma catechol chalone obviously reduce, urinate suprarenin excretion significantly increases.Research finds, the level of plasma C atestatin can prior to the generation of the rising prediction of hypertension of blood pressure, and Catestatin clinical there is hypertension before occur significantly to decline, infer that it may take part in hypertensive onset process.Catestatin can suppress sympathetic activity, reduces blood pressure.The hypotensive effect of Catestatin is also relevant with its suppression Secretion of Catecholamine.Catestatin has powerful regulating effect to blood pressure and heart function, new cardiovascular mark and AD-targeted drugs may be become, but at present about the basis of Catestatin and clinical study still few, mechanism of action and clinical value all need discussion deep further.
(5) coupling factor 6 (CouplingFactor6)
Coupling factor 6 (CouplingFactor6) is a subunit of mitochondrial ATP synthase (ATPsynthase, ATPsyn), and be present in plastosome, in cardiac muscle, content is the highest, is the important component of plastosome energy metabolism.CF6 is a strong vasoconstrictor peptide, the activity of endochylema Phospholipase A2 can be suppressed, reduce the release of plasma membrane arachidonic acid thus affect Epoprostenol Sodium (PGI2) synthesis, be endogenous PGI2 synthesis inhibitory factor unique in hitherto known body, the pathogenic process of hypertension, myocardial ischemia and thrombosis etc. may be participated in.Research finds that the release of ADMA under CF6 effect in mankind's vascular endothelial cell increases, and NO activity reduces.Therefore infer, the increase of CF6 blood plasma level, ADMA is discharged to be increased, and NO generates minimizing, thus raising blood pressure.Separately studies have found that diabetes B patients blood plasma CF6 significantly increases, be negative correlation with blood plasma PGI2 level and be proportionate with blood sugar and blood fat.CF6 level in blood may be the impaired distinguishing mark of endotheliocyte, and can be used as the Hazard Factor promoting that blood vessel injury is new, also may be the factor making diabetic subject's elevation of blood pressure.Coupling factor 6 brings out hypertension by cell oxypathy, and cell oxypathy is relevant with the generation of active oxygen.There is investigator recently, the transgenic mouse of coupling factor 6 process LAN have studied the impact of high salt diet on heart function and the generation of active oxygen, after finding high salt diet, coupling factor 6 can raise heart Triphosphopyridine nucleotide, reduced enzyme, and causing cardiac systolic function abnormal, CF6 may be a risk factor of the core function abnormality caused by hypertension.To sum up, abnormal and the dysequilibrium of network adjustment between multiple humoral factor or vaso-active substance and cause hypertensive generation and development, sometimes be not only single kind of hormone secretion to increase and cause, also may there is secretion and the dysregulation of vasoactive substances.Therefore, be all not enough to illustrate hypertension incidence mechanism and control it develop to the research of single molecule a certain in small-molecular peptides or the treatment of single target spot at present, the network adjustment that therefore must be formed these molecules carries out " integration " research.But the research of the foundation of complex system so far, network adjustment is very difficult, the research method of current functional proteomics is difficult to be suitable for this kind of material, owing to lacking high-throughout investigative technique, also cannot set up the research mode of small-molecular peptides complex system.By setting up relatively simple, the elementary network system, by studying the mutual relationship between this family internal members, and then between more complicated difference ' family ', the regulating networks of even whole body research transition, thus be more deeply familiar with hypertensive pathogenesis, for hypertensive prevention and diagnosis and treatment provide theoretical foundation.
In the prior art, the activity of the action target spot that peptide is hypotensive normally Angiotensin-converting enzyme inhibition (angiotensin-converting enzyme, ACE).Angiotensin-converting enzyme can be angiotensin I converting for having the vasoactive octapeptide Angiotensin II of strong contraction by not having a decapeptide of activity, thus make elevation of blood pressure, therefore suppresses ACE activity effectively can control hypertension.Polypeptide is the important ACE inhibitor of a class, and the Peptides of natural protein is the main source of ACE inhibitor peptide.Angiotensin-converting enzyme plays important regulating effect for body blood pressure and cardiovascular function, therefore suppresses the medicine of ACE activity to play a significant role in the treatment of the disease such as cardiovascular, in heart failure.The ACE inhibitor of polypeptide class can not cause the side effects such as the dry cough of common antihypertensive drugs while hypotensive.
Summary of the invention
The object of this invention is to provide the application of polypeptide in hypotensive and cardioprotection; Polypeptide has hypotensive activity, can as the medicinal application of hypertension, heart trouble and cardiovascular diseases.
For achieving the above object, polypeptide of the present invention its there is aminoacid sequence in sequence table SEQ ID NO:1; Described polypeptide is Altace Ramipril and the active ingredient of medicine providing Cardioprotective, wherein can add acceptable carrier or auxiliary material on pharmacology.
SEQ ID NO:1 sequence is: KRNNFKLVSSMAPAPKVLPVP, is the polypeptide with hypotensive activity, strand linear structure, and white powder is soluble in water, has very strong restraining effect to ACE activity.
The present invention compared with prior art, has following beneficial effect:
The invention provides a kind of biologically active polypeptides, this polypeptide has good application prospect as the medication medication for the treatment of hypertension and Cardioprotective.
Embodiment
The preparation of embodiment 1 SEQ ID NO:1 polypeptide
Adopt conventional polypeptide synthesis method, synthesis obtains corresponding polypeptide, by mass spectrometric detection, confirms to synthesize successfully.
Synthesize of the prior art known to the medicative polypeptide of hypertension: SEQ ID NO:2:VYNEGLPAP simultaneously, by mass spectrometric detection, confirm to synthesize successfully.
The ACE inhibitory activity of embodiment 2 polypeptide detects
ACE 37 DEG C, the simulation substrate Hippuryl-L-Histidyl-L-Leucine (HHL) of catalytic decomposition angiotensin I produces urobenzoic acid under the condition of PH8.3, this material has feature ultraviolet absorption peak at 228nm place.When adding ACE inhibition, the katalysis of ACE to HHL is suppressed, and the growing amount of urobenzoic acid can reduce.The size of inhibit activities can be calculated by measuring the urobenzoic acid ultraviolet absorption value added before and after inhibitor.
Reaction system
Damping fluid is 0.05M, PH8.3 borate buffer solution; Substrate is Hippuryl-L-Histidyl-L-Leucine (HHL), MW 429.47, is made into 5mM with above-mentioned damping fluid; ACE (angiotensin-converting enzyme) is made into 0.1U/ml with above-mentioned damping fluid.ODA (control group, light absorption value during for there is not inhibitor but there is enzyme): 50 μ l damping fluid+50ulHHL+50 μ l damping fluids, in 37 DEG C of water-bath 5min, then add 50 μ lACE, 37 DEG C of water-bath 30min, add 200 μ l, the HCl termination reaction of 1M, then add 1ml extraction into ethyl acetate production of hippuric acid, vibration 15S, the centrifugal 5min of 3500r/min, gets 0.8ml supernatant, 90 DEG C of drying with water bath 15min, heavily be dissolved in 0.Sml distilled water, it is ODA that light absorption value is detected at 228nm place.ODB (sample sets, for existing light absorption value when inhibitor and enzyme): 50 μ l sample+50 μ lHHL+50 μ l damping fluids, in 37 DEG C of water-bath 5min, then add 50 μ lACE, 37 DEG C of water-bath 30min, add 200 μ l, the HCl termination reaction of 1M, then add 1ml extraction into ethyl acetate production of hippuric acid, vibration 15S, the centrifugal 5min of 3500r/min, gets 0.8ml supernatant, 90 DEG C of drying with water bath 15min, heavily be dissolved in 0.8ml distilled water, it is ODB that light absorption value is detected at 228nm place.
ODC (blank group, for there is not light absorption value when inhibitor and enzyme): 50 μ l damping fluid+50 μ lHHL+50 μ l damping fluids, in 37 DEG C of water-bath 5min, then add 50 μ l damping fluids, 37 DEG C of water-bath 30min, add 200 μ l, the HCl termination reaction of 1M, then add 1ml extraction into ethyl acetate production of hippuric acid, vibration 15S, the centrifugal 5min of 3500r/min, gets 0.8ml supernatant, 90 DEG C of drying with water bath 15min, heavily be dissolved in 0.8ml distilled water, it is ODC that light absorption value is detected at 228nm place.
ACE inhibiting rate (%)=(ODA-ODB)/(ODA-ODC) × 100%
Use 0.5mg/ml respectively, the concentration of 0.1mg/ml, 0.01mg/ml, 0.001mg/ml, 0.0001mg/ml, carry out ACE inhibitory activity detection as stated above.Result is as following table:
| Concentration (mg/ml) | SEQ ID NO:1 inhibiting rate (%) | SEQ ID NO:2 inhibiting rate (%) |
| 0.5 | 99.78％ | 93.90％ |
| 0.1 | 90.20％ | 71.89％ |
| 0.01 | 75.87％ | 49.93％ |
| 0.001 | 62.14％ | 34.85％ |
| 0.0001 | 48.48％ | 28.62％ |
As can be seen here, the polypeptide shown in sequence 1 has higher ACE enzyme level effect relative to contrast polypeptide, and this is that polypeptide of the prior art institute is inaccessiable.
The experiment that embodiment 3 polypeptide reduces blood pressure
Get commercial bull spontaneous hypertensive rat as blood pressure measurement model: after injection 0,12,24,48,72h surveys the mouse tail blood pressure of most polypeptide injection group and negative control group, measures 8 times at every turn, gets its mean value.
As can be seen here, the polypeptide of SEQ ID NO:1 has relative to contrast polypeptide the effect better reduced blood pressure, and after continue for the long period, still can keep the characteristic that reduces blood pressure preferably.
Embodiment 4 polypeptide is to the available protecting of heart
By the rat of embodiment 3 after Measure blood pressure, continue cultivation 10 weeks, anaesthetize, carry out cardiac ultrasonic and detect, mainly probe into the systole and diastole the left room chambers of the heart diameter and the thickness of front and rear wall.Find by measuring, SEQ ID NO:1 polypeptide group systole IVSTd (IVSs, 3.01 ± 0.30mm), wall thickness (LVPWs after the systole, 3.37 ± 0.52mm) and diastole IVSTd (IVSd, 2.39 ± 0.20mm), wall thickness (LVPWd after diastole, 2.01 ± 0.38mm) and PBS negative control group (IVSs, 4.02 ± 0.50mm; LVPWs, 3.60 ± 0.26mm; IVSd, LVPWd, 2.93 ± 0.75mm) compare, all obviously thin (P < 0.01), and simultaneously SRQ ID NO:1 group systole, diastole left ventricular interior diameter (LVIDs, 3.87 ± 0.60mm; LVIDd, 5.99 ± 0.50mm) than PBS negative control group (LVIDs, 2.30 ± 0.60mm; LVIDd, 4.48 ± 0.74mm) want large (P < 0.01).Find, above parameter and the control group of the left room of SEQ ID NO:2 polypeptide group SHRs are substantially similar, do not have clear improvement simultaneously.
Embodiment 5 polypeptide is to the available protecting of kidney
The kidney getting SHRs carries out electron microscopy observation; and contrast polypeptide injection group rat kidney pathological manifestations; find that the kidney of SEQ ID NO:2 group rat has comparatively significantly mesangial matrix *; and basement membrane thickened; and SEQ ID NO:1 polypeptide group and PBS group do not have; show it and there is good kidney target organ protection function, also do not find the deposition of obvious immunocomplex simultaneously, show the security of this vaccine.
The security that embodiment 6 SEQ ID NO:1 polypeptide is thin
Get commercial male Wistar rat, 8 week age, adopt 12h/12h illumination and non-limiting full diet.Specifically be divided into 3 groups: SEQ ID NO:1 polypeptide group, SEQ ID NO:2 polypeptide group and blank group, often organize 30.The subcutaneous 3-4 point injection of rat back, only, dosage is only about 300ug/ to 400ul/, strengthens 1 time, totally 4 times after initial immunity every two weeks.Get rat tissue's organ and carry out light microscopic observation, find that organ (lungs, heart, mesentery three grades of arteries, kidney, liver and spleens) the pathology display of SEQ IDNO:1 polypeptide group Wistar rat tissue is without inflammatory cell infiltration, disimmune damages, with negative control group indifference.Kidney electron microscopy observation SEQ ID NO:1 polypeptide group and control group Wistar rat kidney, have no obvious pathological change, all do not find the deposition of high electron density immunocomplex at basilar membrane, and SEQ ID NO:2 polypeptide group has comparatively significantly mesangial matrix *.As can be seen here, SEQ ID NO:1 polypeptide group has good biological safety.
Claims (4)
1. reduce blood pressure and the polypeptide of cardioprotection, its sequence is for shown in SEQ ID NO:1 or 2.
2. a pharmaceutical composition, comprises arbitrary described polypeptide and pharmaceutically acceptable carrier or thinner in the claim 1 for the treatment of significant quantity.
3. pharmaceutical composition according to claim 2 for the preparation for the treatment of hypertensive medicine in utilization.
4. the utilization of pharmaceutical composition according to claim 2 in the medicine for the preparation of cardioprotection while for the treatment of hypertension.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410449896.1A CN104356209A (en) | 2014-08-28 | 2014-08-28 | Polypeptide for reducing blood pressure and protecting heart |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410449896.1A CN104356209A (en) | 2014-08-28 | 2014-08-28 | Polypeptide for reducing blood pressure and protecting heart |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104356209A true CN104356209A (en) | 2015-02-18 |
Family
ID=52523539
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410449896.1A Pending CN104356209A (en) | 2014-08-28 | 2014-08-28 | Polypeptide for reducing blood pressure and protecting heart |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104356209A (en) |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006067163A2 (en) * | 2004-12-22 | 2006-06-29 | Dsm Ip Assets B.V. | Blood pressure lowering oligopeptides in a single enzymatic step |
| CN1894273A (en) * | 2003-12-01 | 2007-01-10 | 明治乳业株式会社 | Peptide inhibiting angiotensin converting enzyme |
| CN101570568A (en) * | 2009-06-15 | 2009-11-04 | 东北农业大学 | ACE inhibitory peptide in fermented milk and preparation method thereof |
| CN101618207A (en) * | 2009-06-17 | 2010-01-06 | 中国科学院大连化学物理研究所 | Application of polypeptide in preparing ACE inhibitor and medicine for lowering blood pressure |
| CN102276694A (en) * | 2011-08-05 | 2011-12-14 | 成都中医药大学 | Blood pressure lowering functional polypeptide from pig blood and application thereof |
| CN102475884A (en) * | 2010-11-29 | 2012-05-30 | 中国科学院大连化学物理研究所 | Application of four polypeptides in preparation ACE inhibitor and antihypertensive drug |
| CN103172698A (en) * | 2013-04-10 | 2013-06-26 | 华东理工大学 | Antihypertensive polypeptides |
| CN103242430A (en) * | 2013-05-31 | 2013-08-14 | 南京中医药大学 | Angiotensin-converting enzyme inhibitory peptide, and preparation method and application thereof |
| CN103275176A (en) * | 2013-06-18 | 2013-09-04 | 天津商业大学 | ACE inhibitory peptide and preparation method thereof |
| CN103923177A (en) * | 2014-04-26 | 2014-07-16 | 宁波大学 | Angiotensin-converting enzyme inhibition peptide sourcing from marine microalgae |
| CN103980347A (en) * | 2014-05-22 | 2014-08-13 | 浙江海洋学院 | Antihypertensive peptide of swim bladder of large yellow croaker and preparation method and use thereof |
-
2014
- 2014-08-28 CN CN201410449896.1A patent/CN104356209A/en active Pending
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1894273A (en) * | 2003-12-01 | 2007-01-10 | 明治乳业株式会社 | Peptide inhibiting angiotensin converting enzyme |
| WO2006067163A2 (en) * | 2004-12-22 | 2006-06-29 | Dsm Ip Assets B.V. | Blood pressure lowering oligopeptides in a single enzymatic step |
| CN101570568A (en) * | 2009-06-15 | 2009-11-04 | 东北农业大学 | ACE inhibitory peptide in fermented milk and preparation method thereof |
| CN101618207A (en) * | 2009-06-17 | 2010-01-06 | 中国科学院大连化学物理研究所 | Application of polypeptide in preparing ACE inhibitor and medicine for lowering blood pressure |
| CN102475884A (en) * | 2010-11-29 | 2012-05-30 | 中国科学院大连化学物理研究所 | Application of four polypeptides in preparation ACE inhibitor and antihypertensive drug |
| CN102276694A (en) * | 2011-08-05 | 2011-12-14 | 成都中医药大学 | Blood pressure lowering functional polypeptide from pig blood and application thereof |
| CN103172698A (en) * | 2013-04-10 | 2013-06-26 | 华东理工大学 | Antihypertensive polypeptides |
| CN103242430A (en) * | 2013-05-31 | 2013-08-14 | 南京中医药大学 | Angiotensin-converting enzyme inhibitory peptide, and preparation method and application thereof |
| CN103275176A (en) * | 2013-06-18 | 2013-09-04 | 天津商业大学 | ACE inhibitory peptide and preparation method thereof |
| CN103923177A (en) * | 2014-04-26 | 2014-07-16 | 宁波大学 | Angiotensin-converting enzyme inhibition peptide sourcing from marine microalgae |
| CN103980347A (en) * | 2014-05-22 | 2014-08-13 | 浙江海洋学院 | Antihypertensive peptide of swim bladder of large yellow croaker and preparation method and use thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Song et al. | Protein kinase C promotes cardiac fibrosis and heart failure by modulating galectin-3 expression | |
| Pacurari et al. | The renin-angiotensin-aldosterone system in vascular inflammation and remodeling | |
| Rai et al. | Downregulation of the apelinergic axis accelerates aging, whereas its systemic restoration improves the mammalian healthspan | |
| Sukumaran et al. | Azilsartan ameliorates diabetic cardiomyopathy in young db/db mice through the modulation of ACE-2/ANG 1–7/Mas receptor cascade | |
| Sakata et al. | Renin angiotensin system-dependent hypertrophy as a contributor to heart failure in hypertensive rats: different characteristics from renin angiotensin system-independent hypertrophy | |
| Nishikimi et al. | Cardioprotective effect of adrenomedullin in heart failure | |
| US20090081274A1 (en) | Mast cell-derived renin | |
| Wu et al. | The role of cardiokines in heart diseases: beneficial or detrimental? | |
| da Silva et al. | Adenosine A2A receptor agonist prevents cardiac remodeling and dysfunction in spontaneously hypertensive male rats after myocardial infarction | |
| Wang et al. | An EP4 receptor agonist inhibits cardiac fibrosis through activation of PKA signaling in hypertrophied heart | |
| Leong et al. | Reversal effects of low-dose imatinib compared with sunitinib on monocrotaline-induced pulmonary and right ventricular remodeling in rats | |
| Carver et al. | Angiotensin‐(1‐7) prevents angiotensin II‐induced fibrosis in cremaster microvessels | |
| Yang et al. | Effects of enalapril on the expression of cardiac angiotensin-converting enzyme and angiotensin-converting enzyme 2 in spontaneously hypertensive rats | |
| Rademaker et al. | Adrenomedullin and heart failure | |
| WO2018026442A1 (en) | Small molecule inhibition for preventing or treating fibrotic diseases | |
| Kompa et al. | Chronic urotensin II receptor antagonist treatment does not alter hypertrophy or fibrosis in a rat model of pressure-overload hypertrophy | |
| Redon et al. | The metabolic syndrome in hypertension | |
| Jin et al. | Inhibiting STAT5 significantly attenuated Ang II-induced cardiac dysfunction and inflammation | |
| JP2022523821A (en) | Istaloxime-containing intravenous formulation for the treatment of acute heart failure (AHF) | |
| Reyes et al. | Angiotensin-(1–12)/chymase axis modulates cardiomyocyte L-type calcium currents in rats expressing human angiotensinogen | |
| Wu et al. | Olmesartan ameliorates pressure overload-induced cardiac remodeling through inhibition of TAK1/p38 signaling in mice | |
| Shao et al. | Inhibitory effect of ethyl acetate extract of Aristolochia yunnanensis on cardiac fibrosis through extracellular signal-regulated kinases 1/2 and transforming growth factor β/small mother against decapentaplegic signaling pathways | |
| CN104356209A (en) | Polypeptide for reducing blood pressure and protecting heart | |
| Miyauchi et al. | Effects of selective endothelin (ET)-A receptor antagonist versus dual ET-A/B receptor antagonist on hearts of streptozotocin-treated diabetic rats | |
| Ito et al. | Activation of Rho-kinase in the brainstem enhances sympathetic drive in mice with heart failure |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150218 |
|
| WD01 | Invention patent application deemed withdrawn after publication |