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Angiotensin-(1-7) receptor Mas agonist ameliorates progress of atherosclerosis in apoE-knockout mice
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نویسنده
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jawien 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.
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منبع
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journal of physiology and pharmacology - 2012 - دوره : 63 - شماره : 1 - صفحه:77 -85
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چکیده
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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.
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کلیدواژه
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Angiotensin-(1-7); ApoE-knockout mice; Atherosclerosis; AVE 0991; Cholesterol; Renin-angiotensin system; Triglycerides
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آدرس
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chair of pharmacology,jagiellonian university medical college,cracow, Poland, chair of pharmacology,jagiellonian university medical college,cracow, Poland, department of histology,jagiellonian university medical college,cracow, Poland, chair of pharmacology,jagiellonian university medical college,cracow, Poland, chair of pharmacology,jagiellonian university medical college,cracow, Poland, chair of pharmacology,jagiellonian university medical college,cracow, Poland, chair of pharmacology,jagiellonian university medical college,cracow, Poland, department of histology,jagiellonian university medical college,cracow, Poland, department of immunology,jagiellonian university medical college,cracow, Poland, department of internal and agricultural medicine,jagiellonian university medical college,cracow, Poland, department of immunology,jagiellonian university medical college,cracow, Poland, chair of pharmacology,jagiellonian university medical college,cracow, Poland, chair of pharmacology,jagiellonian university medical college,cracow, Poland
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Authors
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