title: Angiotensin-(1-7) regulates angiotensin II-induced matrix metalloproteinase-8 in vascular smooth muscle cells.
abstract: Angiotensin II (Ang II) is a bioactive peptide that is related to cardiovascular disease such as atherosclerosis, whereas angiotensin-(1-7) (Ang-(1-7)) is a counter-regulator of angiotensin II, which protects against cardiovascular disease. Matrix metalloproteinase 8 (MMP-8) is thought to participate in plaque destabilization though degradation of extracellular matrix, improving the development of atherosclerosis. Whether Ang-(1-7) modulates Ang II-induced MMP-8 remains unclear. In this study, we investigated the effect of Ang-(1-7) on Ang II-induced MMP-8 expression in smooth muscle cells.
  
  
  
  Smooth muscle cells were treated with Ang II, Ang-(1-7) and their antagonists. In addition, ApoE knockout mice were fed a high fat diet and subcutaneously injected with Ang II, Ang-(1-7), Ang II+Ang-(1-7) (±A779).
  
  
  
  We found that Ang II increased MMP-8 mRNA and protein expression in vascular smooth muscle cells, while Ang-(1-7) alone had no effect. However, Ang-(1-7) inhibited Ang II-induced MMP-8 expression. The inhibitory effect of Ang-(1-7) could be abolished by the competitive antagonist of Ang-(1-7) at the MAS receptor. Furthermore, Ang II induced p38 MAPK activation, and this was inhibited by the treatment of Ang-(1-7). Ang II-induced MMP-8 expression could be attenuated by the p38 MAPK inhibitor SB203580. Ang-(1-7) also significantly suppressed Ang II-induced MMP-8 in both atherosclerotic plaques and serum in ApoE-/-mice. The atherosclerotic plaques in mice treated with Ang-(1-7) and Ang II appeared to be more stable with more type I collagen contents than those in mice treated with Ang II.
  
  
  
  Our results suggest that Ang-(1-7) plays an important role in protecting against atherosclerosis via counter-regulation of Ang II-induced MMP-8.
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China.
authors.forename: Junxian
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China. Electronic address: chenhongbj@medmail.com.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006801:Humans; D020784:Matrix Metalloproteinase 8 / Q000235:genetics / Q000378:metabolism*; D000074085:Mice, Knockout, ApoE; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D058226:Plaque, Atherosclerotic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D000803:Angiotensin I; D048051:p38 Mitogen-Activated Protein Kinases; C488762:MMP8 protein, human; C576328:MMP8 protein, mouse; D020784:Matrix Metalloproteinase 8; C118790:angiotensin I (1-7)
keywords: Angiotensin; Matrix metalloproteinase-8; Smooth muscle cell