ADAMTS-4 And Vascular Endothelial Growth Factor(VEGF) And The Study On The Relationship Between The Stability Of Atherosclerotic Plaques

Atherosclerosis(Atherosclerosis,AS)is a chronic,progressive,inflammatory related artery disease,mainly involving large,elastic artery,it is a lipid deposition,inflammatory cells infiltration and migration of smooth muscle cells,extracellular matrix degradation is a prominent feature.Its pathogenesis is not yet clear,a number of experimental evidence show that coronary atherosclerosis in endothelial cell dysfunction,for initial event progress to a series of inflammatory cytokines(IL-1 beta,TNF alpha,MCP-1,IL-8,ICAM 1,VCAM 1,etc.),matrix protease(MMPs,Tryptase/Chymase,Serine proteinases plasminogen activator and plasminogen,Cathepsins,ADAMTSs,etc.)involved in,accompanied by chronic vascular inflammation cell hyperplasia.Acute coronary syndrome(Acute coronary syndrome,ACS)is coronary atherosclerosis end-stage performance outcome.Several studies have shown that coronary atherosclerosis plaque rupture and secondary thrombosis,lead to coronary artery lumen narrowed sharply or totally occluded,it's unstable angina,acute myocardial infarction and sudden cardiac death in the main pathophysiological mechanisms.Atherosclerotic plaque lesions within macrophages composition determines the process of atherosclerosis,decided the atheromatous plaque stability,and is closely related to thrombosis complications.Four closely connected,but independent of the process control in atherosclerotic plaques in macrophages composition change,Are: chemical chemotaxis,adhesion,migration and differentiation,apoptosis(foam cells).At home and abroad a large number of data show that chemical chemokine in endothelial cells or other the expression of atherosclerosis related cells increases,for the progress of atherosclerosis and plaque stability to have more far-reaching consequences.ADAMTSs is the recent discovery of a new members of the family of metalloproteinases,its molecular structure and protein hydrolysis is similar to the MMPs.Both contain peptide enzyme in zinc dependent,participate in the ECM protein hydrolysis.Unlike MMPs,ADAMTSs to integrin and structure domain and platelet response element structure domain.The latest findings.ADAMTS-4 in human atherosclerosis carotid plaque and coronary artery of unstable plaque high expression in the parts that are rich in macrophages.However,its expression in atherosclerotic artery is very low.Atheromatous plaque in macrophages.Invasion of macrophages in plaque of the fibrous cap,the plaque is more fragile,it has to do with macrophages to secrete proteolytic enzyme degradation of ECM in thin fibrous cap.Therefore we conclude that the unstable plaque macrophages in the rich area ADAMTS4 high expression,its action may also be similar to the MMPs,through the degradation of ECM in thin fibrous cap,and then induce the plaque rupture.Vascular endothelial growth factor(VEGF)is found that the specificity of the strongest angiogenesis factors,Have prompted the role of vascular permeability increase at the same time,growth factor and inflammatory factor [1],a lack of oxygen,etc all can stimulate the endothelial cells,smooth muscle cells,and macrophages to secrete VEGF.Now think of VEGF in ischemia,inflammation,tumor has physiological and pathological role in carcinogenesis,it can promote angiogenesis and collateral circulation formation.clinical research has confirmed that the increased level of VEGF expression in unstable plaques,the ACS severity is related,it can accelerate the process of atherosclerosis,clinical judgment is plaque stability and the occurrence,development and prognosis of acute coronary syndrome(ACS)important serological markers.But VEGF induced plaque unstable concrete mechanism has not yet been related research.Objective: The first part: discussing ADAMTS-4 in the stable plaque and unstable plaques of expression.Compare ADAMTS-4 expression differences in stable plaques and unstable plaques.Understand ADAMTS-4(human autopsy specimens)unstable plaques in the expression,to determine if it can be as the histological indexes of judging the stability of plaque.The second part: to study the vascular endothelial growth factor(VEGF)expression in stable plaques and unstable plaques.Methods: select autopsy extract with acute coronary syndrome(ACS)specimens as ACS group,choose not acute coronary syndrome(ACS)or the specimens with old myocardial infarction as control group,Take the left,right coronary artery respectively wax block.The first part of the immunohistochemical(IHC)method to detect ADAMTS-4 and VEGF expression differences in plaque and unstable plaque stabilization and its expression.The second part by immunohistochemical(IHC)method to detect VEGF expression differences in plaque and unstable plaque stabilization and its expression.Results: The first part: the ADAMTS-4 in plaque rupture site expression(91.75±6.64)is significantly enhance hemal wall and vascular smooth muscle cells,ADAMTS-4 show lower expression in the plaques surrounding tissue(16.08±2.37),Have obvious statistical significance difference(P < 0.05).ADAMTS-4 most were highly expressed in ACS group(95.67±7.84),and most are not showing in the control group(8.17±1.74),a handful of lower expression Have obvious statistical significance difference(P < 0.05).The second part: VEGF in plaque rupture site expression(90.13 + 6.18)obviously increased in the blood vessels and vascular smooth muscle cells and VEGF in plaque around also have moderate expression in vascular smooth muscle cells(72.24 + /-5.11),no obvious statistical significance difference(P > 0.05).VEGF in ACS group(93.46 + 7.29)for the vast majority are in high expression,and in the control group(10.47 + 2.19)most shows don't express,a handful of lower expression.Conclusion: 1.ADAMTS-4 and VEGF is highly expressed in unstable plaques,and expression is not obvious in the stable plaque,and macrophages in the unstable plaque area high expression of rich?2.VEGF in plaques are expressed in the peripheral vascular smooth muscle cells.