Effect of atorvastatin on the angiogenic responsiveness of coronary endothelial cells in normal and streptozotocin (STZ) induced diabetic rats.
Atorvastatin, a lipid lowering agent, possesses various pleiotropic vasculoprotective effects, but its role in coronary angiogenesis is still controversial. Our objective was to study the effects of atorvastatin on the angiogenic responsiveness of coronary endothelial cells (cEC) from normal and diabetic rats. Male Wistar rats were distributed among 9 groups; (i) normal rats, (ii) 30 day diabetic rats, (iii) 60 day diabetic rats, (iv) normal rats administered a low dose of atorvastatin (1 mg/kg body mass, per oral (p.o.), for 15 days); (v) 30 day diabetic rats administered a low dose of atorvastatin; (vi) 60 day diabetic rats administered a low dose of atorvastatin; (vii) normal rats administered a high dose of atorvastatin (5 mg/kg, p.o., for 15 days); (viii) 30 day diabetic rats administered a high dose of atorvastatin; (ix) 60 day diabetic rats administered a high dose of atorvastatin. Each group was further divided into 2 subgroups, (i) sham ischemia-reperfusion and (ii) rats hearts that underwent ischemia-reperfusion. Angiogenic responsiveness the and nitric oxide (NO) releasing properties of the subgroups of cECs were studied using a chorioallantoic membrane assay and the Griess method, respectively. Atorvastatin treatment significantly increased VEGF-induced angiogenic responsiveness and the NO-releasing properties of cECs from all of the subgroups, compared with their respective non-treated subgroups except for the late-phase diabetic rat hearts that underwent ischemia-reperfusion, and the high dose of atorvastatin treatment groups. These effects of atorvastatin were significantly inhibited by pretreatment of cECs with l-NAME, wortmannin, and chelerythrine. Thus, treatment with a low dose of atorvastatin improves the angiogenic responsiveness of the cECs from normal and diabetic rats, in the presence of VEGF, via activation of eNOS-NO release.
a Department of Pharmacology, L.M. College of Pharmacy, Opp. Gujarat University, Navarangpura, Ahmedabad 380009, India.
Kiranj K
KK
Chaudagar
Anita A
AA
Mehta
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000069059:Atorvastatin; D053119:Benzophenanthridines / Q000494:pharmacology; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D000924:Anticholesteremic Agents; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D006538:Heptanoic Acids; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D013311:Streptozocin; D000069059:Atorvastatin; C016299:chelerythrine; D019331:NG-Nitroarginine Methyl Ester; D000077191:Wortmannin