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Journal of Cardiovascular Pharmacology and Therapeutics
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1074248409343690v1
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Article

MMP-2 and MMP-9 Alteration in Response to Collaring in Rabbits: The Effects of Endothelin Receptor Antagonism

Buket Reel, PhD1, Gulgun Oktay, PhD2, Sermin Ozkal, MD3, Huray Islekel, MD2, Erdener Ozer, MD3, Gonen Ozsarlak-Sozer, PhD1, Zahide Cavdar, PhD2, Serpil Tanriverdi Akhisaroglu, MD2, and Zeliha Kerry, PhD1*

1 Ege University Faculty of Pharmacy, Bornoza, Izmir, Turkey
2 Department of Biochemistry, School of Medicine, Dokuz Eylul University, Inciralti, Izmir, Turkey
3 Department of Pathology, School of Medicine, Dokuz Eylul University, Inciralti, Izmir, Turkey

* To whom correspondence should be addressed. E-mail: zeliha.kerry{at}ege.edu.tr.


   Abstract

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.

First published on September 4, 2009, doi:10.1177/1074248409343690

Journal of Cardiovascular Pharmacology and Therapeutics 2009;14:292.

A more recent version of this article appeared on December 1, 2009


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