title: Angiotensin-(1-7) receptor Mas agonist ameliorates progress of atherosclerosis in apoE-knockout mice.
abstract: 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.
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, Cracow, Poland. mmjawien@cyf-kr.edu.pl
authors.forename: J
authors.initials: J
authors.lastname: Jawien
authors.forename: J
authors.initials: J
authors.lastname: Toton-Zuranska
authors.forename: M
authors.initials: M
authors.lastname: Gajda
authors.forename: A
authors.initials: A
authors.lastname: Niepsuj
authors.forename: A
authors.initials: A
authors.lastname: Gebska
authors.forename: K
authors.initials: K
authors.lastname: Kus
authors.forename: M
authors.initials: M
authors.lastname: Suski
authors.forename: G
authors.initials: G
authors.lastname: Pyka-Fosciak
authors.forename: B
authors.initials: B
authors.lastname: Nowak
authors.forename: T J
authors.initials: TJ
authors.lastname: Guzik
authors.forename: J
authors.initials: J
authors.lastname: Marcinkiewicz
authors.forename: R
authors.initials: R
authors.lastname: Olszanecki
authors.forename: R
authors.initials: R
authors.lastname: Korbut
mesh_terms: D000803:Angiotensin I / Q000819:agonists* / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000819:agonists* / Q000378:metabolism; D020913:Perindopril / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000819:agonists* / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000819:agonists* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D015244:Thiorphan / Q000494:pharmacology
chemical_list: C469726:AVE 0991; D015703:Antigens, CD; D001057:Apolipoproteins E; D007093:Imidazoles; D008055:Lipids; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011945:Receptors, Angiotensin; D043562:Receptors, G-Protein-Coupled; D000803:Angiotensin I; D015244:Thiorphan; C118790:angiotensin I (1-7); D020913:Perindopril