A Probe Into The Impact Of MMP-2 And MMP-9 Upon The Stability Of Atherosclerotic Plaques In Internal Carotid Artery

Objective: Carotid artery stenosis refers to carotid artery intima injuries regardless of any causes.These injuries lead to deposition of lipid material and blood cells in the blood which can cause discontinuity of arterial intima and intimal smooth muscle hyperplasia.Growth of connective tissue,deposition of intracellular and extracellular cholesterol,fatty acid and calcium carbonate and the gathering of collagen and proteoglycan will destroy the normal structure of artery wall.Eventually the arterial diameter becomes thinner,causing the entire arteries lose elasticity.Matrix metalloproteinase 2(MMP-2),also known as gelatinase A,has wide expressions in human body and can cause degradation of gelatin,multiple collagen and basement membrane composition.It plays an important role in proliferation and migration of smooth muscle cells.MMP-2 can specifically cause degradation of Type I and Type II collagen into smaller fragments,and degrade a variety of extracellular matrix,including fibronectin,elastin,protein sugar,etc.MMP-2 has a low collagenase activity in solution compared with MMP-1 and other matrix metalloproteinases.But its precursor can effectively cause collagen degradation on cell surface.Matrix metalloproteinase-9(MMP-9),also known as gelatinase B,is also a member of matrix metalloproteinases(MMPs).It is one of the major mediators of extracellular matrix degradation.MMP-9 is mainly expressed in atherosclerotic plaque,plaque basal vascular membrane and atherosclerotic lesion of smooth muscle cells,macrophages and endothelial cells.Meanwhile,MMP-9 also plays an important role in vascular regeneration.However,clinical study of MMP-2 and MMP-9 impacts upon stability of carotid atherosclerosis plaque is relatively less than other studies.We design and carry out this experiment and try to explore the expression of MMP-2 and MMP-9 in human carotid atherosclerotic plaque and relationship between MMP-2 and MMP-9 and the stability of atherosclerotic plaque.Method:1 Selection of specimens for experiment43 plaque specimens are chosen from the internal carotid artery endarterectomy cases finished in the Department of Neurosurgery of The No.2 Affiliated Hospital of Hebei Medical University during March,2014 to September,2015.These plaque tissues are HE stained and divided into two groups under light microscope: an unstable plaque group and a stable plaque group.The former consists of 20 cases from 17 male and 3 females,average age of 66.4 years old;the latter consists of 23 cases from 19 males and 4 female,average age of 59.9 years old.2 Distribution,location and quantitative analysis of MMP-2 and MMP-9 in internal carotid atherosclerotic plaquesTo detect the expression of MMP-2 and MMP-9 in the above defined two groups of plaque tissues using immunohistochemical method.We use Image-Pro-Plus5.0 software to analyze the above mentioned quantitative indexes of carotid artery plaques.Result:1 Under the microscope the expression of MMP-2 and MMP-9 can be observed in vascular smooth muscle cells,vascular endothelial cells,foam cells and macrophages in plaque tissues,especially in macrophages and foam cells where large number of expression of MMP-2 and MMP-9 are found.Expressions are more obvious in plaque shoulder area than in other parts.2 Immunohistochemical test of MMP-2 and MMP-9 expressions and quantitative analysis: the expressions of MMP-2 and MMP-9 in the stable group are different from those in the unstable group and the differences are of statistical significance(P<0.01).Conclusion:1 The expression of MMP-2 and MMP-9 in the unstable plague group is obviously higher than that in the stable group and the difference between these two groups is significant(P < 0.01).This shows that the level of MMP-2 and MMP-9 expression in plaques clearly correlated with plague stability.MMP-2 and MMP-9 are important factors to form unstable plaques.2 The level of MMP-2 and MMP-9 expression in the unstable plaques is much higher than in the stable plaques,and one of the important components in the fibrous cap is extracellular matrix.Both MMP-2,MMP-9 can cause degradation of extracellular matrix.Therefore,the increased expression of MMP-2 and MMP-9 is bound to increase degradation of collagen fibers and connective tissues in the fibrous cap of atheromatous plaques,which can lead to thinning of the fibrous cap or even fibrous cap rupture.