title: MMP-2 and MMP-9 alteration in response to collaring in rabbits: the effects of endothelin receptor antagonism.
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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Ege University, Bornova, Izmir, Turkey.
authors.forename: Buket
authors.initials: B
authors.lastname: Reel
authors.forename: Gulgun
authors.initials: G
authors.lastname: Oktay
authors.forename: Sermin
authors.initials: S
authors.lastname: Ozkal
authors.forename: Huray
authors.initials: H
authors.lastname: Islekel
authors.forename: Erdener
authors.initials: E
authors.lastname: Ozer
authors.forename: Gonen
authors.initials: G
authors.lastname: Ozsarlak-Sozer
authors.forename: Zahide
authors.initials: Z
authors.lastname: Cavdar
authors.forename: Serpil Tanriverdi
authors.initials: ST
authors.lastname: Akhisaroglu
authors.forename: Zeliha
authors.initials: Z
authors.lastname: Kerry
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000201:enzymology; D003324:Coronary Artery Disease / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000378:metabolism; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011817:Rabbits; D017539:Tunica Intima / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D065128:Endothelin Receptor Antagonists; D004792:Enzyme Precursors; D010456:Peptides, Cyclic; C088196:TAK 044; D018093:Gelatinases; C069860:progelatinase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9