MMP-2 and MMP-9 alteration in response to collaring in rabbits: the effects of endothelin receptor antagonism
Autor: | Buket Reel, Sermin Özkal, Serpil Tanriverdi Akhisaroglu, Hüray İşlekel, Gulgun Oktay, Gonen Ozsarlak-Sozer, Zeliha Kerry, Erdener Özer, Zahide Cavdar |
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Rok vydání: | 2009 |
Předmět: |
Endothelin Receptor Antagonists
Male Gelatinases medicine.medical_specialty Coronary Artery Disease Matrix metalloproteinase Peptides Cyclic Restenosis Internal medicine medicine Gelatinase Animals Pharmacology (medical) Receptor Pharmacology Enzyme Precursors Cell growth business.industry Anatomy medicine.disease Enzyme Activation Disease Models Animal Endocrinology Carotid Arteries Matrix Metalloproteinase 9 Matrix Metalloproteinase 2 Female Rabbits Cardiology and Cardiovascular Medicine Antagonism Endothelin receptor business Tunica Intima |
Zdroj: | Journal of cardiovascular pharmacology and therapeutics. 14(4) |
ISSN: | 1940-4034 |
Popis: | Matrix metalloproteinases (MMPs), and, in particular, gelatinases (MMP-2 and MMP-9), have been implicated in vascular cell proliferation and/or migration, contributing to intimal thickening, an essential stage in the development of atherosclerosis and restenosis following balloon angioplasty. Endothelin, a strong chemoatractant and mitogen, has been shown to promote smooth muscle cell proliferation and migration by activating MMPs via endothelin-A (ETA) receptors. The positioning of a soft silicon collar around the left carotid artery in rabbits results in intimal thickening. In this study, we investigate the possible role of gelatinases and the effect of a nonselective ETA/ETB receptor antagonist, TAK-044 (5 mg/kg body weight/day, subcutaneously [sc]), on these enzymes. Our results demonstrated that both MMP-2 and MMP-9 activities increased in response to collaring in placebo group, while treatment with TAK-044 significantly suppressed both gelatinase activities and proMMP-2 levels, and inhibited intimal thickening in collared arteries. These results suggest that either enhanced MMP expression or endothelin receptor antagonism may be involved in the formation of intimal thickening in this model. |
Databáze: | OpenAIRE |
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