MMP-2 and MMP-9 alteration in response to collaring in rabbits: the effects of endothelin receptor antagonism.
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.
Reel
Buket
B
Department of Pharmacology, Faculty of Pharmacy, Ege University, Bornova, Izmir, Turkey.
Oktay
Gulgun
G
Ozkal
Sermin
S
Islekel
Huray
H
Ozer
Erdener
E
Ozsarlak-Sozer
Gonen
G
Cavdar
Zahide
Z
Akhisaroglu
Serpil Tanriverdi
ST
Kerry
Zeliha
Z
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
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