Losartan Regulate The Expression Of Angiotensin-Convertion Enzyme 2 And The Effects In Rabbit Atherosclerotic Plaques

ObjectiveTo investigate regulation of the expression of angiotensin-convertion enzyme 2 and the effect of losartan in atherosclerotic plaques.MethodsThirty-six male New Zealand White rabbits were underwent balloon-induced arterial wall injury and fed with hige-cholesterol diet for 12 weeks to construct a atherosclerosis model.They are randomly and equally assigned to 3 groups:high cholesterol group(n=12),fed with high-cholesterol diet alone to 12 weeks;losartan group(n=12):fed with high-cholesterol diet to 12 weeks+losartan(25mg/kg·d) for 28 days;losartan+A779 group(n=12):fed with high-cholesterol diet to 12 weeks+losartan(25mg/kg·d)+injected with A779 100ng/(kg·d) through Ear vein for 28 days.There are 3 rabbits died during the time.We detect the concentration of serum TC,LDL-C at 0 week and 12 weeks.The thoracic aorta were harvested.We used HE staining,Oil red O staining,Masson staining to observe the morphology of thoracic aorta,lipid of atherosclerotic plaques and Collagen content of atherosclerotic plaques.We use immunohistochemical staining to measure the expression of ACE2,Ang-(1-7) proteins and macrophage.Data of nine animals in each group to choose to do statistical analysis.Results1 The results of lipid:The concentration of serum TC,LDL-C in high-cholesterol group,losartan group,losartan+A779 group at 12 weeks were significantly higher than it at 0 weeks(P＜0.01);Comparing the concentration of serum TC,LDL-C,There was no statistical difference between two groups(P＞0.05).losartan and A779 have no effect to lipid.2 The extent of atherosclerosis compared of each groupThe intima thickness,I/M thickness,intima area and I/M area of losartan group are less than high-cholesterol group(P＜0.05);The data of losartan+A779 group are larger than losartan group's(P＜0.05).There is no difference between losartan+A779 group and high-cholesterol group(P＞0.05).3 Lipid of atherosclerotic plaques in Each groupAtherosclerotic plaques contain clear lipid which stained red.The Lipid content in plaques of high-cholesterol group,losartan group and losartan +A779 group are (30.47±1.83)%,(22.92±2.41)%,(32.52±2.88)%.The Lipid content of losartan group is less than high-cholesterol group and losartan +A779 group(P＜0.05).There is no difference between losartan+A779 group and high-cholesterol group(P＞0.05).4 The protein expression of ACE2 and Ang-(1-7) and detection of macrophage cells:There are many tufted macrophage-positive cells in abdominal aorta plaque.The expression of losartan group are less than high-cholesterol group(P＜0.05);The expression of losartan +A779 group are more than losartan group's(P＜0.05).There is no difference between losartan+A779 group and high-cholesterol group(P＞0.05).Both angiotensin-convertion enzyme 2 and Angiotensin-(1-7) express in abdominal aorta plaque.A large proportion of macrophage-positive cells and a percentage of smooth muscle cells,endothelia within atherosclerotic plaques expressed ACE2 protein.Angiotensin-(1-7) is present in extracellular.Results Analysis of immunohistochemical staining:The expression of ACE2 and Angiotensin-(1-7)of losartan group and losartan+A779 group were higher than that of high-cholesterol group(P＜0.05).However,there is no difference between losartan group and losartan +A779 group(P＞0.05).5 Collagen content of atherosclerotic plaques in Each group The collagen content in plaques of high-cholesterol group,losartan group and losartan +A779 group are(13.64±2.39)%,(20.43±2.13)%,(13.75±1.75)%.There are more collagen in abdominal aorta plaque of losartan group than high-cholesterol group(P＜0.05).The collagen of losartan +A779 group are more than losartan group's (P＜0.05).There is no difference between losartan +A779 group and highcholesterol group(P＞0.05).Conclusions1.Losartan treatment can significantly reduce the extent of atherosclerosis;2 Losartan treatment can significantly improve the expression of ACE2 and Ang-(1-7) in Rabbit atherosclerotic plaques;3.Losartan can inhibit atherosclerosis through improve the expression of ACE2 protein then increase Ang-(1-7) level.A779—the specific receptor antagonist of Ang-(1-7)can block this effect.