Effects Of Perindopril And Enalapril On Atherosclerosis Development Of Apolipoprotein E Knockout Mice

ObjectiveTo investigate the effects of angiotensin converting enzyme(ACE) inhibitors on the development of atherosclerotic lesions,particularly on the composition of plaque,in ApoE knockout mice,and to compare the different effects between perindopril and enalapril.MethodsApoE knockout mice were treated with perindopril(1.5mg·kg^-1·d^-1, n=20),or enalapril(7.5 mg·kg^-1·d^-1,n=20)or saline(0.2 ml/d,n=20) per gavage for 20 weeks.Blood pressure and lipids were measured at the study end.Aortic root atherosclerotic plaque was then quantified and the content of collagen and the size of lipid core in the plaque were assessed. Cryostat sections were used to quantify the expressions of monocyte/macrophage-2(MOMA-2),intercellular adhesion molecule-1 (ICAM-1),vascular cell adhesion molecule-1(VCAM-1) and matrix metalloproteinases-9(MMP-9) in the plaque by immunofluorescence method. ResultsBlood pressure and lipid profiles were similar among different groups.Compared with control group,the plaque areas of perindopril group and enalapril group displayed significant decrease(25.33%and 22.86%,respectively,both P＜0.01).However,no significant differences were observed in the plaque size between the different ACE inhibitor groups.It was demonstrated that in perindopril group and enalapril group the size of lipid core significantly decreased(52.98%and 38.98%, respectively,both P＜0.01) and the expression of MOMA-2(88.38%and 52.16%,respectively,both P＜0.01),ICAM-1(80.87%and 49.59%, respectively,both P＜0.01),VCAM-1(77.56%and 56.44%,respectively, both P＜0.01) and MMP-9(86.93%and 55.56%,respectively,both P＜0.01) also significantly decreased,and the plaque collagen content increased significantly(298.36%and 168.14%,respectively,both P＜0.01) and the effects of perindopril were superior to those of enalapril(all P＜0.05).ConclusionsACE inhibitors significantly suppressed tissue inflammation and attenuated the development of atherosclerosis in ApoE knockout mice independent of their effects on the lipid and blood pressure.Perindopril is superior to enalapril in stabilizing the plaques and has similar effect on reducing the plaque size as that of enalapril. ObjectiveTo investigate the effects of perindopril on the development of atherosclerotic lesions in coronary artery and aortic root of ApoE knockout mice.MethodsTwenty ApoE knockout mice were randomly divided into two groups:perindoprilor group(1.5mg·kg^-1·d^-1,n=10) and control group (saline,0.2 ml/d,n=10).These mice were sacrificed after 20 weeks.The plaque areas of coronary artery and aortic root were measured after the sections were stained with a modified Movat pentachrome stain.ResultsCompared with control group,plaque areas of coronary artery (81599±6041μm² and 65718±5059μm²,respectively,P＜0.01) and aortic root(937678±90445μm² and 700148±72537μm²,respectively, P＜0.01) in perindopril group were significantly decreased.The plaque areas of coronary artery were positively correlated with the plaque areas of aortic root in perindopril group(r=0.791,P＜0.01).The plaque areas of coronary artery were also positively correlated with the plaque areas of aortic root in control group(r=0.721,P＜0.05).ConclusionsPerindopril not only decreases plaque areas of coronary artery but also decreases plaque areas of aortic root.The plaque areas of coronary artery are closely correlated with the plaque areas of aortic root.