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

Department of Pharmacology, Faculty of Pharmacy, Ege University, Bornova, Izmir, Turkey

Gulgun Oktay, PhD

Department of Biochemistry, Ege University, Bornova, Izmir, Turkey

Sermin Ozkal, MD

Department of Pathology, School of Medicine, Dokuz Eylul University, Inciralti, Izmir, Turkey

Huray Islekel, MD

Department of Biochemistry, Ege University, Bornova, Izmir, Turkey

Erdener Ozer, MD

Department of Pathology, School of Medicine, Dokuz Eylul University, Inciralti, Izmir, Turkey

Gonen Ozsarlak-Sozer, PhD

Department of Pharmacology, Faculty of Pharmacy, Ege University, Bornova, Izmir, Turkey

Zahide Cavdar, PhD

Department of Biochemistry, Ege University, Bornova, Izmir, Turkey

Serpil Tanriverdi Akhisaroglu, MD

Department of Biochemistry, Ege University, Bornova, Izmir, Turkey

Zeliha Kerry, PhD

Department of Pharmacology, Faculty of Pharmacy, Ege University, Bornova, Izmir, Turkey, zeliha.kerry{at}ege.edu.tr

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.

Key Words: atherosclerosis • matrix metalloproteinase • endothelin antagonism • rabbit • collar

This version was published on December 1, 2009

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 14, No. 4, 292-301 (2009)
DOI: 10.1177/1074248409343690


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