Uric acid stimulates proliferative pathways in vascular smooth muscle cells through the activation of p38 MAPK, p44/42 MAPK and PDGFRβ.

Kırça M., OĞUZ N., ÇETIN A., UZUNER F., Yeşilkaya A.

Journal of receptor and signal transduction research, cilt.37, ss.167-173, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 37
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1080/10799893.2016.1203941
  • Dergi Adı: Journal of receptor and signal transduction research
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.167-173
  • Anahtar Kelimeler: Ang II, p38 MAPK, p44, 42 MAPK, PDGFR beta, uric acid, VSMC, ANGIOTENSIN-II, CARDIOVASCULAR-DISEASE, ESSENTIAL-HYPERTENSION, PROTEIN-KINASE, ENDOTHELIAL DYSFUNCTION, INDEPENDENT MECHANISM, URATE TRANSPORTER, OXIDATIVE STRESS, BLOOD-PRESSURE, RENAL-DISEASE
  • Akdeniz Üniversitesi Adresli: Evet

Özet

Hyperuricemia and angiotensin II (Ang II) may have a pathogenetic role in the development of hypertension and atherosclerosis as well as cardiovascular disease (CVD) and its prognosis. The purpose of this study was to investigate whether uric acid can induce proliferative pathways of vascular smooth muscle cell (VSMC) that are thought to be responsible for the development of CVD. The phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), p44/42 mitogen-activated protein kinase (p44/42 MAPK) and platelet-derived growth factor receptor beta (PDGFR beta) was measured by Elisa and Western blot techniques to determine the activation of proliferative pathways in primary cultured VSMCs from rat aorta. Results demonstrated that uric acid can stimulate p38 MAPK, p44/42 MAPK and PDGFR phosphorylation in a time- and concentration-dependent manner. Furthermore, treatment of VSMCs with the angiotensin II type I receptor (AT1R) inhibitor losartan suppressed p38 MAPK and p44/42 MAPK induction by uric acid. The stimulatory effect of uric acid on p38 MAPK was higher compared to that of Ang II. The results of this study show for the first time that uric acid-induced PDGFR beta phosphorylation plays a crucial role in the development of CVDs and that elevated uric acid levels could be a potential therapeutical target in CVD patients.