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

REEL B., OKTAY G., ÖZKAL S., İŞLEKEL G. H., ÖZER E., ÖZŞARLAK SÖZER G., ...Daha Fazla

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS, cilt.14, sa.4, ss.292-301, 2009 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 14 Sayı: 4
  • Basım Tarihi: 2009
  • Doi Numarası: 10.1177/1074248409343690
  • Dergi Adı: JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.292-301
  • Anahtar Kelimeler: atherosclerosis, matrix metalloproteinase, endothelin antagonism, rabbit, collar, MUSCLE-CELL-MIGRATION, MATRIX-METALLOPROTEINASE EXPRESSION, CAROTID-ARTERY, ATHEROSCLEROTIC LESIONS, VASCULAR REACTIVITY, BALLOON ANGIOPLASTY, ACTIVATION, RAT, PROLIFERATION, INJURY
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

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.