title: Angiotensin-(1-7) ameliorates myocardial remodeling and interstitial fibrosis in spontaneous hypertension: role of MMPs/TIMPs.
abstract: Angiotensin-(1-7) displays antihypertensive and antiproliferative properties although its effect on cardiac remodeling and hypertrophy in hypertension has not been fully elucidated. The present study was designed to examine the effect of chronic angiotensin-(1-7) treatment on myocardial remodeling, cardiac hypertrophy and underlying mechanisms in spontaneous hypertension. Adult male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were treated with or without angiotensin-(1-7) or the angiotensin-(1-7) antagonist A-779 for 24 weeks. Mean arterial pressure, left ventricular geometry, expression of the hypertrophic markers ANP and β-MHC, collagen contents (type I and III), collagenase (MMP-1), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of MMPs-1 (TIMP-1) were evaluated in WKY and SHR rats with or without treatment. Our data revealed that chronic angiotensin-(1-7) treatment significantly suppressed hypertension, left ventricular hypertrophy, expression of ANP and β-MHC as well as myocardial fibrosis in SHR rats, the effects of which were nullified by the angiotensin-(1-7) receptor antagonist A-779. In addition, angiotensin-(1-7) treatment significantly counteracted hypertension-induced changes in the mRNA expression of MMP-2 and TIMP-1 and collagenase activity, the effects of which were blunted by A-779. In vitro study revealed that angiotensin-(1-7) directly increased the activity of MMP-2 and MMP-9 while decreasing the content of TIMP-1 and TIMP-2. Taken together, our results revealed a protective effect of angiotensin-(1-7) against cardiac hypertrophy and collagen deposition, which may be related to concerted changes in MMPs and TIMPs levels. These data indicated the therapeutic potential of angiotensin-(1-7) in spontaneous hypertension-induced cardiac remodeling.
authors.affiliation: Department of Cardiology, The Third Hospital, Nanchang, Jiangxi, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Pei
authors.forename: Rongsen
authors.initials: R
authors.lastname: Meng
authors.forename: Guangwei
authors.initials: G
authors.lastname: Li
authors.forename: Guangmei
authors.initials: G
authors.lastname: Yan
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Zhenbiao
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000032:analysis / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000517:prevention & control*; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D005355:Fibrosis; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000032:analysis / Q000235:genetics; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis / Q000502:physiology*
chemical_list: D000959:Antihypertensive Agents; C000594638:MYH7 protein, rat; D010446:Peptide Fragments; D019714:Tissue Inhibitor of Metalloproteinases; D009320:Atrial Natriuretic Factor; D003094:Collagen; D000803:Angiotensin I; D017364:Collagenases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D018995:Myosin Heavy Chains; C118790:angiotensin I (1-7)