Effect of uric acid on inflammatory COX-2 and ROS pathways in vascular smooth muscle cells

OGUZ N., Kirca M., Cetin A., YEŞİLKAYA A.

JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION, cilt.37, sa.5, ss.500-505, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 37 Sayı: 5
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1080/10799893.2017.1360350
  • Dergi Adı: JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.500-505
  • Anahtar Kelimeler: Uric acid, COX-2, superoxide, VSMC, inflammation, losartan, OXIDATIVE STRESS, ANGIOTENSIN-II, ESSENTIAL-HYPERTENSION, PROTEIN-KINASE, CYCLOOXYGENASE-2, PROLIFERATION, DISEASE, HYPERURICEMIA, INDUCTION, LOSARTAN
  • Akdeniz Üniversitesi Adresli: Evet

Özet

Hyperuricemia is thought to play a role in cardiovascular diseases (CVD), including hypertension, coronary artery disease and atherosclerosis. However, exactly how uric acid contributes to these pathologies is unknown. An underlying mechanism of inflammatory diseases, such as atherosclerosis, includes enhanced production of cyclooxygenase-2 (COX-2) and superoxide anion. Here, we aimed to examine the effect of uric acid on inflammatory COX-2 and superoxide anion production and to determine the role of losartan. Primarily cultured vascular smooth muscle cells (VSMCs) were time and dose-dependently induced by uric acid and COX-2 and superoxide anion levels were measured. COX-2 levels were determined by ELISA, and superoxide anion was measured by the superoxide dismutase (SOD)-inhibitable reduction of ferricytochrome c method. Uric acid elevated COX-2 levels in a time-dependent manner. Angiotensin-II receptor blocker, losartan, diminished uric-acid-induced COX-2 elevation. Uric acid also increased superoxide anion level in VSMCs. Uric acid plays an important role in CVD pathogenesis by inducing inflammatory COX-2 and ROS pathways. This is the first study demonstrating losartan's ability to reduce uric-acid-induced COX-2 elevation.