CN106390142A - Function and application of IRF5 (interferon regulatory factor-5) and IRF5 inhibitor in treatment of restenosis after VI (vascular injury) - Google Patents
Function and application of IRF5 (interferon regulatory factor-5) and IRF5 inhibitor in treatment of restenosis after VI (vascular injury) Download PDFInfo
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Abstract
The invention discloses a function and an application of an IRF5 (interferon regulatory factor-5) and an IRF5 inhibitor in treatment of restenosis after VI (vascular injury). An IRF5 gene knockout mouse and a wild mouse are taken as experimental subjects, detection of intima neogenesis, vessel wall cell proliferation level and smooth muscle cell phenotype transformation of the mice are performed through a VI model, and results show that IRF5 gene knockout can obviously inhibit intima neogenesis and cell proliferation and inhibit transformation of smooth muscle cells from contractile phenotype to synthetic phenotype. Therefore, the function of the IRF5 on treatment of restenosis after VI mainly lies in promoting intima neogenesis, cell proliferation and smooth muscle cell phenotype transformation. Based on the function of the IRF5, the IRF5 can be taken as a drug target to be used for screening drugs for preventing and treating restenosis after VI, and the IRF5 inhibitor can be used for preparing a drug and an arterial stent for preventing and treating restenosis after VI.
Description
Technical field
The invention belongs to the function of gene and application, particularly to a kind of interferon regulatory factor 5 (interferon
Regulatory factor-5, IRF5) the answering in the medicine of screening treatment angiostenosis after damage as drug targets
With.
Background technology
Change with the developing rapidly of human social economy, the raising of living standards of the people and dietary structure and population
Aging process, the incidence of disease of angiocardiopathy raises year by year, it has also become the great disease of the global public health of serious harm
One of disease.Neointimal formation is atherosclerotic (atherosclerosis, AS), pulmonary hypertension, percutaneous coronary
The blood vessels such as PCI (percutaneous transluminal coronary intervention, PCI) postoperative restenosis
The pathologic process that proliferative vascular disease has.New intima and middle membrane tissue hyperplasia and simultaneously adjoint extracellular base
Matter is formed, and is the main pathological basis causing ISR.VSMC (vascular smooth muscle
Cells, VSMCs) Phenotypic Change plays important role during Neointimal formation.After injury of blood vessel, vascular smooth
Myocyte is migrated from middle film to inner membrance, the Proliferation and apoptosis loss of equilibrium of smooth muscle cell, and phenotype is changed from shrinkage type to synthesis type, blood
Tube wall discomfort is reinvented, thus causing endometrial hyperplasia.This kind of disease be there is no at present with radical cure method, the primary treatment hand of vascular surgery
Section is inaccessible section reconstructing blood vessel, inserts including balloon expandable, support and arterial bypass etc. is although blood vessel weight can be realized
Build, the artery that effectively dredging is blocked, improve blood supply, but the incidence of ISR higher (30～60%) after reconstructing blood vessel,
Greatly have impact on therapeutic effect, so far after reconstructing blood vessel, ISR is still a clinical problem.
Current research is known as, and interferon regulatory factor family is the main regulation adjusting immunity and cell survival conditions
The factor, by 9 member compositions [1-3] in mammal body.IRF5 is the important a member in IRFs family, it be initially from
Clone in the DC library of people and obtain, have now been found that expression in many immune cell type, such as macrophage, dendron shape is thin
Born of the same parents, B cell and monocyte [4].Similar to IRF1, due to there are 2 functional nuclear localization sequences (NLSs), IRF5 is usual
Express [5] in the nucleus do not stimulate cell.Research finds：Main Factors Blimp- by suppression regulation and control plasma cell differentiation
1 expression, IRF5 promote B cell maturation, IRF5 lack B cell can reduce cytokine induction to IgG2a/c's
Conversion [6].Its base in the growth of Th1 cell and the differentiation of macrophage is identified in the immunoregulatory research of IRF5 further
This function [7].Clinical investigation shows there be close contacting between IRF5 and various autoimmune disease, such as systemic red yabbi
Sore, inflammatory bowel disease, and rheumatoid arthritis [8].During inflammatory reaction, it is wide that IRF5 plays in panimmunity cell
General and main effect, is verified by building IRF5 knock-out mice, it is mainly shown as the minimizing of dead cell number
Release with the proinflammatory factor of endotaxin induction shock mediation.
Bibliography
1.Tamura, T., Yanai, H., Savitsky, D.＆Taniguchi, T.The IRF family
Transcription factors in immunity and oncogenesis.Annu.Rev.Immunol.26,535 584
(2008).
2.Ikushima, H., Negishi, H.＆Taniguchi, T.The IRF family transcription
factors at the interface of innate and adaptive immune responses.Cold Spring
Harb.Symp.Quant.Biol.78,105 116 (2013).
3.Yanai, H., Negishi, H.＆Taniguchi, T.The IRF family of transcription
factors:Inception, impact and implications in oncogenesis.Oncoimmunology 1,
1376–1386(2012).
4.Ryzhakov G,Eames HL,Udalova IA(2015)Activation and function of
interferon regulatory factor 5.J Interferon Cytokine Res 35:71-78doi:10.1089/
jir.2014.0023
5.Barnes BJ,Kellum MJ,Field AE,Pitha PM(2002)Multiple regulatory
domains of IRF-5control activation,cellular localization,and induction of
chemokines that mediate recruitment of T lymphocytes.Mol Cell Biol 22:5721-
5740
6.Fang CM,Roy S,Nielsen E,Paul M,Maul R,Paun A,Koentgen F,Raval FM,
Szomolanyi-Tsuda E,Pitha PM(2012)Unique contribution of IRF-5-Ikaros axis to
the B-cell IgG2a response.Genes Immun 13:421-430doi:10.1038/gene.2012.10
7.Tamura T,Yanai H,Savitsky D,Taniguchi T(2008)The IRF family
transcription factors in immunity and oncogenesis.Annu Rev Immunol 26:535-
584doi:10.1146/annurev.immunol.26.021607.090400
8.Xu WD,Pan HF,Xu Y,Ye DQ(2013)Interferon regulatory factor 5and
autoimmune lupus.Expert Rev Mol Med 15:e6doi:10.1017/erm.2013.7
9.Takaoka A,Yanai H,Kondo S,Duncan G,Negishi H,Mizutani T,Kano S,
Honda K,Ohba Y,Mak TW,Taniguchi T(2005)Integral role of IRF-5in the gene
induction programme activated by Toll-like receptors.Nature 434:243-249doi:
10.1038/nature03308
Content of the invention
For solving defect and the deficiency of above-mentioned prior art, it is an object of the invention to determining that the expression of IRF5 and blood vessel damage
The correlation of ISR after wound, provides a kind of IRF5 as drug targets in the medicine screening prevention of restenosis after vascular injury
In application, and then provide a kind of inhibitor of IRF5 preparation prevention of restenosis after vascular injury medicine in application.
The purpose of the present invention is achieved through the following technical solutions：
The present invention, with wild type C57BL/6 mouse and IRF5 knock out mice (IRF5-KO mouse) as experimental subjects, is led to
Cross the induction of arteria carotis seal wire damage model and obtain mouse vascular injury model (vascular injury, VI), carry out blood vessel damage
Wound model (VI) mouse neointima measures, the detection of the detection of cells of vascular wall propagation level and smooth muscle cell phenotype and grinding
Study carefully.Result shows：Contrast with wild type C56BL/6 mouse, IRF5 knock out mice shows neointima and cell proliferation
It is significantly less than WT mouse；IRF5 gene knockout can suppress proliferating cell nuclear antigen (Proliferating Cell Nuclear
Antigen, PCNA) and cyclin (Cyclin D1) expression, the propagation of smooth muscle cell and inner membrance can be suppressed to increase
Raw；IRF5 gene knockout can promote SMC differentiation specific antigen (smoothelin), smooth muscle actin
(Smooth Muscle Actin, SMA) and the expression of Smoothing Probablities (smooth muscle 22alpha, SM22 α), can press down
Smooth muscle cell processed from shrinkage type to the Phenotypic change of synthesis type, thus suppressing endometrial hyperplasia.The above results show IRF5 gene
Knockout can suppress the generation of angiostenosis after damage, and IRF5 can promote the formation of angiostenosis after damage, pre- for research
Novel targets that are anti-, alleviating and/or treat angiostenosis after damage and New Policy provide theoretical foundation and Clinical Basis.
Therefore, IRF5 gene as drug target, can build In vitro cell model or the animal mould of IRF5 gene overexpression
Type, for the medicine of screening prevention, alleviation and/or treatment angiostenosis after damage；IRF5 gene also can be used as gene therapy
In target gene, design and prepare prevention, alleviate and/or treatment angiostenosis after damage medicine.For example with IRF5 as target
Gene, design may interfere with double-strand siRNA of IRF5 expression, after being chemically synthesized, is injected into human body and is disturbed by RNA
Method make IRF5 gene silencing treat angiostenosis after damage；Can also design and build the mutant of IRF5, injection
Entering cell, the substrate specificity of competition IRF5 original shape afterwards, thus suppressing the function of IRF5, playing therapeutic purposes；Further, it is also possible to
With IRF5 for shot design micromolecular compound inhibitor, using external model or the animal model of IRF5 gene overexpression, lead to
Cross screening, find wherein to be capable of the molecule of specificity suppression IRF5, thus new for the treatment offer of angiostenosis after damage
Therapeutic molecules.
For the above-mentioned functions of IRF5, IRF5 is provided to treat the medicine of angiostenosis after damage in screening as drug targets
Application in thing.
For the above-mentioned functions of IRF5, the inhibitor providing IRF5 is in the medicine of preparation treatment angiostenosis after damage
Application.
A kind of medicine of protection vascular function, comprises the inhibitor of IRF5.
A kind of medicine treating angiostenosis after damage, comprises the inhibitor of IRF5.
The arterial bracket of a kind of prevention, alleviation and/or treatment angiostenosis after damage, it is coated with the suppression of IRF5
Agent.
The inhibitor of described IRF5 is preferably the rna interference vector of siRNA, IRF5 gene of IRF5 gene, IRF5's
Antibody and other can suppress one of inhibitor of IRF5 expression.
In the present invention, described injury of blood vessel is mainly vessel injury.
In the present invention, described injury of blood vessel refers to the injury of blood vessel that atherosclerotic causes, or in treatment artery
The injury of blood vessel causing when atherosis, for example, pass through balloon expandable or put into the injury of blood vessel that support causes, or after transplanting
The injury of blood vessel that arteriopathy or pulmonary hypertension cause.
In the present invention, described atherosclerotic had both included the hemadostewnosis phase that atherosclerotic is compared with commitment,
Also include atherosclerotic serious when the blood vessel obstruction phase.
In the present invention, described arterial bracket refers to, for supporting human body internal cause pathology and narrow, inaccessible blood vessel, recover
The tubular device of blood circulation, is made using metal or processing of high molecular material, can stay in human vas for a long time or temporarily.?
On the basis of tube chamber balloon expandable shapes, support stenosis occlusion section blood vessel, reduce blood vessel bullet to reach in lesion Stent Implantation
Property retraction and more moulding, keep the unobstructed purpose of tube chamber blood flow, both included peripheral arterial support, also included coronary stent.
In the present invention, described ISR refers to that done leads to vessel lumen again when local vascular occurs to damage
Narrow generality biologically.Here refer mainly to the reangiostenosis that iatrogenic injury causes, damage process is mainly by moving
Arteries and veins is reinvented and endotheliosis composition.
The present invention has such advantages as with respect to prior art and effect：
(1) present invention discover that the New function of IRF5 gene, that is, IRF5 has the effect deteriorating angiostenosis after damage.
(2) function in angiostenosis after damage is being deteriorated based on IRF5, it is to develop prevention, alleviate and/or treat
The medicine of angiostenosis after damage provides target.
(3) inhibitor of IRF5 can be used for preparing the medicine of prevention, alleviation and/or treatment angiostenosis after damage.
(4) inhibitor of IRF5 can be used for prepare prevention, alleviate and/or treatment angiostenosis after damage artery prop up
Frame.
Brief description
Fig. 1 is WT and IRF5-KO mouse postoperative 14 days and the EVG of 28 days dyes and Intimal area result statistics block diagram；
Wherein, A：EVG colored graph, B：Intimal area counts block diagram (*：P ＜ 0.05vs WT VI group).
Fig. 2 is WT and IRF5-KO mouse postoperative 14 days and the horizontal mark PCNA of 28 days cells of vascular wall propagation,
The immunofluorescence dyeing of CyclinD1 expression and result statistics block diagram；
Wherein, A：Immunofluorescence dyeing, B：Result counts block diagram (*：P ＜ 0.05vs WT VI group).
Fig. 3 is WT and IRF5-KO mouse postoperative 14 days and 28 days smooth muscle cell phenotype transition flag thing smoothelin,
The immunofluorescence dyeing of SMA, SM22 alpha expression and result statistics block diagram；
Wherein, A：Immunofluorescence dyeing, B：Block diagram (*：P ＜ 0.05vs WT VI group).
Specific embodiment
By combination accompanying drawing described further below it will be further appreciated that the features and advantages of the invention.The enforcement being provided
Example is only the explanation to the inventive method, and limits remaining content of present invention announcement never in any form.
Animal for research and raising
Animal used as test：From 8-10 week old, body weight in 24-27g, male, (WT mouse, purchased from Beijing China for C57BL/6 mouse
Fukang bio tech ltd), (IRF5-KO, purchased from U.S. The Jackson Laboratory for IRF5 knock out mice
Company, article No.：017311).
Feeding environment：All experiment mices are all raised in Wuhan University SPF level Experimental Animal Center.SPF level mouse feed
Purchased from Beijing Fukang bio tech ltd of China, rearing conditions：Room temperature between 22-24 DEG C, humidity between 40-70%,
It is 12h that light and shade replaces lighting hours, and free water is ingested.
【Embodiment 1】Mouse vascular injury model (VI) obtains
1. animal used as test packet：Using 8-10 week old, WT the and IRF5-KO mouse of body weight 24-27g, respectively it is divided into 2 groups：WT
Injury of blood vessel group, IRF5-KO injury of blood vessel group, every group of each 20 mouse.Put to death mouse within 14 days and 28 days after surgery respectively, take
Damage segmental vessels to be analyzed.
2. mouse vascular injury model operating process：
1) accurately weigh Mouse Weight (g) under dynamic mode with electronic balance, with distilled water accurately configuration 3% penta bar ratio
Appropriate sodium solution, is shaken gently for making it fully dissolve, using 80mg/kg body weight dose, Nembutal sodium solution volume needed for calculating
Accurately extract respective volume solution, row intraperitoneal injection of anesthesia mouse with 1mL syringe afterwards, treat that mouse fully anaesthetizes down (about 3min)
Afterwards, 8% vulcanized sodium neck depilation.
2) separate in neck and external carotid artery.
3) prick external carotid artery in internal carotid and external carotid artery crotch with 8-0 knot, use simultaneously blood vessel clip (WPI,
501784-G) temporary blocking-up internal carotid and arteria carotis communis blood supply.
4) use microscissors (WPI, 501839) one osculum of Transverse Shear above ligation of external carotid artery line.Cut through this blood vessel
The seal wire (No.C-SF-15-15, Cook, Bloomington, Indiana) of mouth 0.015 inch of diameter of insertion, rotation seal wire enters
Move back 5-6 time.
5) ligature external carotid artery in otch proximal end to heart, unclamp in neck and arteria carotis communis puts the blood vessel clip staying, cut off the end of a thread, clearly
Reason visual area, sutures cervical incision.
【Embodiment 2】Vascular injury model (VI) mouse neointima measures
1. mouse is drawn materials
1) anesthetized mice, breaks heart bloodletting.
2) cut arteria carotis from the nearly crotch of arteria carotis, take 0.5-0.6cm length, retain external carotid artery knot.
3) arteria carotis is put in PBS, softly drain intraluminal residual blood with microforceps.
4) blood vessel is put into equipped with fixing in the 1.5mL EP pipe of 1mL 4% paraformaldehyde.
2. pathology detection
2. pathology detection
2.1 prepare paraffin specimen section
Paraffin specimen section is prepared by laboratory profession pathology staff, primary operational program includes：4% paraformaldehyde
In after fixation overnight, blood vessel filter paper is carefully wrapped, puts into embedding frame → flowing water flushing → dehydration → transparent → waxdip → bag
Bury → cut into slices standby after the piece → dry or toast of (3 μm) → stand.
2.2EVG dyeing
Mainly comprise the following steps：55 DEG C of baking 30min → dimethylbenzene 5min, 3 times → 100% alcohol 3min, 2 times → 95% alcohol
3min, 1 time → 70% alcohol 3min, 1 time → distilled water 1min → liquor potassic permanganate 5min (Zhuhai shellfish rope, BA-4083B) →
Washing 1min → oxalic acid solution 5min (Zhuhai shellfish rope, BA-4083B) → washing 1min → 95% alcohol differentiation 2-3 second →
Elastin dye liquor (Zhuhai shellfish rope, BA-4083B) 8-24 hour → 95% alcohol breaks up rapidly 1s → flowing water and rinses 10min → bis-
Steam water 1min → Van Gieson dye liquor (Zhuhai shellfish rope, BA-4083B) 1min → 95% alcohol and break up rapidly 2-3s → 100%
Alcohol 2min, 2 times → dimethylbenzene 2min, 3 times → take advantage of in the not dry mounting → fume hood immediately of dimethylbenzene and dry up, microscope is taken pictures.
With Ink vessel transfusing elastic fibers and outer elastic fibers as boundary, it is endangium within interior elastic plate, beyond outer elastic plate
For externa, it is tunicae media vasorum between inside and outside elastic plate.Enclose each vessel lumen with Image-Pro Plus 6.0 software respectively
Area.
The calculating of Intimal area size is as follows with reference to formula：
Neointimal area=interior elastic force plate suqare-Lumen Area；
Media area=outer elastic force plate suqare-interior elastic force plate suqare.
The newborn result such as Fig. 1 of endangium after mouse EVG dyeing.Normal wall structures are complete, marshalling,
Endangium is monolayer endothelial cell, structural integrity, middle film smooth muscle cell marshalling.Observed by HE dyeing, blood vessel
Damage group (VI group) wall structures are imperfect, and vascular endothelial cell lacks, and neointimal hyperplasia is obvious, and with a large amount of inflammation
Cellular infiltration；IRF5-KO group 14 days after surgery, 28 days neointimal area substantially will reduce than WT mouse.Equally, lining endothelium
The ratio of long-pending/media area will be less than WT group in VI postoperative IRF5-KO group.The disappearance of this explanation IRF5 gene can suppress blood vessel
The neointima causing after damage.
【Embodiment 3】Cells of vascular wall breeds the detection of level
Immunofluorescence dyeing detection proliferating cell nuclear antigen (Proliferating Cell Nuclear Antigen,
PCNA), the expression of cyclin (Cyclin D1).A required anti-information：PCNA(#2586；1:100；mouse；Cell
Signaling Technology), cyclin D1 (#2978；1:25；rabbit；Cell Signaling Technology)；
Required two anti-information：Alexa Fluor 568-conjugated goat anti-rabbit IgG(A11011；
Invitrogen, Carlsbad, CA), Alexa Fluor 568-conjugated goat anti-mouse IgG
(A11004；Invitrogen,Carlsbad,150d,CA).
Mainly comprise the following steps：
1) bake piece：Paraffin section is placed in more than 60min in 55 DEG C of baking boxs.
2) dewax：Dimethylbenzene 8min × 3.
3) it is hydrated：100% ethanol 5min × 2；95% ethanol 5min；70% ethanol 5min；ddH2O embathes 5min × 2.
4) citrate tissue antigen recovery (Pressure method)：Take a certain amount of pH6.0 citrate antigen retrieval work
In repairing in box, the amount of repair liquid must be able to liquid (stepping neoformation Science and Technology Ltd., article No. MVS-0100 purchased from Foochow)
Whole section of submergence enough, puts in the pressure cooker adding appropriate running water by repairing box, and big fire is heated to seething with excitement, and will dewax
Histotomy after hydration is placed on high temperature resistant staining rack, then staining rack is slowly put in reparation box, covers pot cover, buckles pressure
Power valve, continues to be heated to jet, after starting timing 5min, pressure cooker deenergization, goes valve to uncap, takes out and repair box；Room temperature is put
Section is taken out after putting 20min natural cooling.
5)ddH2O rinses 5min × 2 time, and PBS rinses 5min × 2 time.
6) groupization stroke circle, dropping 10% donkey serum (GTX27481, GeneTex) closing, 37 DEG C of closings in wet box
60min.
7) abandon confining liquid, the one of dropping proper proportion dilution resists, 4 DEG C of overnight incubation, 37 DEG C of rewarming 30min discard one and resist,
PBS washes 8min × 4 time.
8) dropping two resists, 37 DEG C of incubation 60min in wet box, discards two and resists, PBS embathes 5min × 4 time.
9) SlowFade Gold antifade reagent with DAPI (S36939, Invitrogen) mounting.
10) viewed under fluoroscopy, takes pictures.If needing to preserve, 4 DEG C of preservations in dark wet box.
Fluorescence statistical method：PCNA immunofluorescence dyeing statistics is counted using IPP software, and PCNA positive cell percentage=
Total DAPI number * 100% of PCNA positive cell number/(inner membrance+middle film)；CyclinD1 immunofluorescence dyeing statistics adopts
Positive absorbance directly surveyed by IPP software.
Immunofluorescence technique observes smooth muscle cell proliferation mark PCNA, CyclinD1 in WT and IRF5-KO mouse blood vessel
Expression change after damage, result is shown in Fig. 2.PCNA, CyclinD1 have expression in vascular tissue, and IRF5-KO mouse is after surgery
The fluorescence intensity of 14 days, the positive cell number of 28 days PCNA and CyclinD1 is intended to be reduced to the WT mouse with group, shows
IRF5 gene knockout can suppress the expression of PCNA, CyclinD1, and the propagation of smooth muscle cell and endangium can be suppressed newborn.
【Embodiment 4】The detection of smooth muscle cell phenotype
Immunofluorescence dyeing detects SMC differentiation mark：SMC differentiation specific antigen
(smoothelin), smooth muscle actin (Smooth Muscle Actin, SMA), Smoothing Probablities (smooth muscle
22alpha, SM22 α) expression.A required anti-information：SMA(ab5694；1:100；rabbit；Abcam)and SM22α
(ab14106；1:100；rabbit；Abcam)；Required two anti-information：Alexa Fluor 488-conjugated goat
anti-rabbit IgG(A11008；Invitrogen,Carlsbad,CA).
Key step is with reference to embodiment 3.
Fluorescence statistical method：Positive absorbance is directly surveyed using IPP software.
Under normal physiological condition, VSMC remains static, and is mainly shown as shrinkage type；Injury of blood vessel
Afterwards, VSMC is migrated from middle film to inner membrance, the Proliferation and apoptosis loss of equilibrium of smooth muscle cell, and phenotype is from shrinkage type to conjunction
Shaping changes, and vascular wall discomfort is reinvented, thus causing endometrial hyperplasia.Immunofluorescence observes smoothelin, SMA, SM22 α in WT
Change with the expression after IRF5-KO mouse injury of blood vessel, result is shown in Fig. 3.Smoothelin, SMA, SM22 α is in vascular tissue
There is expression, IRF5-KO mouse 14 days after surgery, the fluorescence intensity of 28 days smoothelin, SMA, SM22 α are all higher than with group
WT mouse, shows that IRF5 gene knockout can promote the expression of smoothelin, SMA, SM22 α, can suppress smooth muscle cell by
Shrinkage type is to the Phenotypic change of synthesis type, thus suppressing endometrial hyperplasia.
Above example result shows, wild-type mice and IRF5-KO mouse are under the induction of vascular injury model (VI)
All there is angiostenosis after damage.The neointima of IRF5 knock out mice, cell proliferation level and smooth muscle cell
Phenotypic change is all inconspicuous than wild-type mice.These results indicate that the smooth muscle that IRF5 can increase injury of blood vessel induction is thin
The propagation of born of the same parents, Phenotypic Change and blood vessel neointima are formed.
Above-described embodiment is the present invention preferably embodiment, but embodiments of the present invention are not subject to above-described embodiment
Limit, other any Spirit Essences without departing from the present invention and the change made under principle, modification, replacement, combine, simplify,
All should be equivalent substitute mode, be included within protection scope of the present invention.
Claims (5)
- The application in the medicine of screening prevention of restenosis after vascular injury as drug targets of 1.IRF5 gene.
- 2. according to claim 1 application it is characterised in that：Described medicine is the medicine of suppression IRF5 gene expression； Described application is non-diagnostic and non-treatment.
- 3. according to claim 1 and 2 application it is characterised in that：Described injury of blood vessel is atherosclerotic, artery The injury of blood vessel that atherosis PCI, transplanting arteriopathy or pulmonary hypertension cause.
- 4. a kind of arterial bracket of prevention of restenosis after vascular injury is it is characterised in that be coated with the inhibitor of IRF5.
- 5. according to according to claim 4 application it is characterised in that：Described injury of blood vessel is atherosclerotic, moves The injury of blood vessel that pulse atherosclerosis PCI, transplanting arteriopathy or pulmonary hypertension cause.
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