Effects of hyperglycemia on angiotensin II induced Jak2 and STAT 1 phosphorylations and role of PDGF beta receptor on this pathway in rat aortic vascular smooth muscle cells

ABSTRACTOne of the basic underlying causes of diabetic atherosclerosis appears to behyperglycemia-(HG) induced vascular smooth muscle cell (VSMC) proliferation.Jak/STAT pathway and Ang II contribute the VSMC proliferation. In this study, weaimed to observe Ang II induced Jak2 and STAT1 activition under hyperglycemicconditions. In addition we aimed to observe the PDGF receptor activition and effectsof PKC on Ang II induced Jak/STAT phosphorylation.In the end of the study, the presence of cultured rat aortic VSMCs wereconfirmed immunohistochemically with smooth muscle alpha-actin antibodies. AngII stimulated Jak2 and STAT1 phosphorylation in 100 nM concentrations of Ang IIin 5 minutes is maximum and the observed phosphorylation through AT1 reseptorwas demonstrated using AT1 receptor inhibitor losartan. We observed that, VSMCscultured in a high glucose environment for 48 hours increases both basal and Ang IIinduced Jak2 and STAT1 proteins than low glucose environment. We used in ourexperiments spesific PDGF-β receptor inhibitor AG1295 and PKC inhibitorGF109203X and found that high glucose levels increased Ang II stimulated Jak2 andSTAT1 phosphorylations independent of PDGF-β receptor and PKC. According toour findings Ang II stimulated Jak2 ve STAT1 phosphorylation does not proceed viaPDGF receptor. It is also demonstrated in this study that PKC does not effect Jak2and STAT1 phosphorylation.Key Words: Angiotensin II, high glucose, vascular smooth cells, Jak2,STAT1, PDGF-β receptor, Protein kinase C.