Carvedilol, a pharmacological antioxidant, inhibits neointimal matrix metalloproteinase-2 and -9 in experimental atherosclerosis.

Carvedilol, a pharmacological antioxidant, inhibits neointimal matrix metalloproteinase-2 and -9 in experimental atherosclerosis. Research Abstract Details 

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Carvedilol, a pharmacological antioxidant, inhibits neointimal matrix metalloproteinase-2 and -9 in experimental atherosclerosis. Abstract Text:

Tao-Cheng Wu,Yung-Hsiang Chen,Hsin-Bang Leu,Yuh-Lien Chen,Feng-Yen Lin,Shing-Jong Lin,Jaw-Wen Chen,Tao-Cheng Wu,Yung-Hsiang Chen,Hsin-Bang Leu,Yuh-Lien Chen,Feng-Yen Lin,Shing-Jong Lin,Jaw-Wen Chen,Tao-Cheng Wu,Yung-Hsiang Chen,Hsin-Bang Leu,Yuh-Lien Chen,Feng-Yen Lin,Shing-Jong Lin,Jaw-Wen Chen,

Matrix metalloproteinase (MMP) is critical to the progression of atherosclerosis and neointima hyperplasia after vascular injury. We investigated the effects of carvedilol, a pharmacological antioxidant with alpha- and beta-adrenergic blocking activity, on MMP-2 and MMP-9 expression. Vascular injury was induced with the balloon catheters on abdominal aortas of high-cholesterol-fed rabbits. On Day 21, there was significant aortic neointima formation with increased oxidative DNA damage by immunostaining with 8-hydroxy-2'-deoxyguanosine and enhanced MMP-2 and MMP-9 expressions by Western blotting, which were significantly reduced by oral administration of carvedilol (20 mg/kg/day) or probucol (100 mg/kg/day). Vascular expression (by Western blot), activity (by gelatin zymography), and mRNA levels of MMP-2 and MMP-9 were also reduced by carvedilol or probucol. Besides, pretreatment with carvedilol or probucol but not propranolol, a beta-blocker, or prazocin, an alpha-blocker, inhibited tumor necrosis factor-alpha-stimulated expressions and activities of MMP-2 and MMP-9 in human aortic smooth muscle cells. On electrophoretic mobility-shift assay, carvedilol inhibited the binding activities of activator protein-1 and specific protein-1, two major transcription factors for MMP promoter regions. Accordingly, carvedilol, a pharmacological antioxidant, inhibited in vivo and in vitro expression of MMP-2 and MMP-9 properly by modulating the redox-related pathways, suggesting its potential clinical implications.

Carvedilol, a pharmacological antioxidant, inhibits neointimal matrix metalloproteinase-2 and -9 in experimental atherosclerosis. Publishing Authors By Initials

TC Wu,YH Chen,HB Leu,YL Chen,FY Lin,SJ Lin,JW Chen,TC Wu,YH Chen,HB Leu,YL Chen,FY Lin,SJ Lin,JW Chen,TC Wu,YH Chen,HB Leu,YL Chen,FY Lin,SJ Lin,JW Chen,

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Carvedilol, a pharmacological antioxidant, inhibits neointimal matrix metalloproteinase-2 and -9 in experimental atherosclerosis. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Free radical biology & medicine

VOLUME: 43

Page Numbers: 1508-22

Journal Abbreviation: Free Radic. Biol. Med.

ISSN: 0891-5849

DAY: 24

MONTH: 08

YEAR: 2007

Carvedilol, a pharmacological antioxidant, inhibits neointimal matrix metalloproteinase-2 and -9 in experimental atherosclerosis. Information

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LANGUAGE: eng

NlmUniqueID: 8709159

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Grant and Affiliation Information for Carvedilol, a pharmacological antioxidant, inhibits neointimal matrix metalloproteinase-2 and -9 in experimental atherosclerosis.

AFFILIATION: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.

Country: United States

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MEDLINETA: Free Radic Biol Med

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