Angiotensin-(1-7) receptor Mas agonist ameliorates progress of atherosclerosis in apoE-knockout mice

Our interest focused on an open question whether at-(1-7),nonpeptide receptor agonist: ave 0991,is able to ameliorate atherosclerosis. we used an apolipoprotein e (apoe) - knockout mice model of atherosclerosis. experimental groups received the same diet as control,mixed with: ave 0991 at a dose of 0.58 μmol/kg b.w./day,perindopril at a dose of 0.4 mg/kg b.w./day or with tiorphan at a dose of 2.5 mg/kg b.w./day. a-779 [(d-alanine)- angiotensin (1-7)] was given at a dose of 3.3 mg/kg b.w.,3 times a week i.p. measured by en face method,the percentage of occupied by sudan iv-stained surfaces were as follows: 14.2±1.9% in control group,whereas in ave 0991-treated as well as in perindopril-treated groups percentages were statistically significantly lower. in tiorphan group there was no change comparing to control group,whereas in a-779 group percentage was statistically significantly higher. cross-section of aortic roots revealed also the difference in atherosclerotic lesions. the mean surfaces,occupied by oil red o-stained changes were: 91.213±8.123 μm 2 in control group,while in ave 0991-treated as well as in perindopril-treated groups lesions were statistically significantly lower. in tiorphan group there was no change; however,in a-779 group lesions were statistically significantly higher. measured by real time rt-pcr relative p22phox (submit of nadph oxidase) expression was significantly decreased in ave 0991-treated mice. as revealed by flow cytometry,the expression of co-stimulatory molecules: cd86,cd80 and cd40 on both dendritic cells (cd11c+) and macrophages (f4/80+) was reduced in ave 0991-treated group,which correlated with decreased expression of cd69 activation marker on cd4+t cells. in our report we showed the beneficial effect of ave 0991 on atherogenesis in gene-targeted mice.