ANGIOTENSIN-(1-7) RECEPTOR Mas AGONIST AMELIORATES PROGRESS OF ATHEROSCLEROSIS IN apoE-KNOCKOUT MICE

作者：Jawen J^*; Toton Zuranska J; Gajda M; Niepsuj A; Gebska A; Kus K; Suski M; Pyka Fosciak G; Nowak B; Guzik T J; Marcinkiewicz J; Olszanecki R; Korbut R

来源：Journal of Physiology and Pharmacology, 2012, 63(1): 77-85.

• angiotensin-(1-7)
• renin-angiotensin system
• apoE-knockout mice
• atherosclerosis
• AVE 0991
• cholesterol
• triglycerides

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 mu mol/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 %26quot;en face%26quot; 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. %26quot;Cross-section%26quot; 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 mu m(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.

• 出版日期2012-2