Rosuvastatin promotes angiogenesis and reverses isoproterenol-induced acute myocardial infarction in rats: role of iNOS and VEGF.
Several reports highlighted the cardioprotective effect of statins after different types of ischemic injury. We studied the effect of rosuvastatin on acute myocardial infarction induced experimentally in rats focusing on angiogenesis as a potential mechanism underlying the drug effect. Acute myocardial infarction was induced by injecting the rats with two doses of isoproterenol (85 mg/kg/24 h, s.c.). Rats were examined for their electrocardiographic pattern and myocardial fibrosis one week after injection of isoproterenol (time for initiating therapy) and eight weeks thereafter (the end of therapeutic period) to examine the progression of the injury. Examination of the heart tissues at the end of week 9 showed a non significant decrease in the degree of myocardial fibrosis compared to those observed at week 1, indicating a slow rate of recovery from isoproterenol-induced injury. Treatment with rosuvastatin (5 or 10 mg/kg) for 8 weeks in myocardial-infarct rats enhanced the electrocardiographic pattern, reduced serum cardiac biomarkers, reduced tissue tumor necrosis factor-α (TNF-α) and upregulated vascular endothelial growth factor (VEGF) level. In addition, immunohistochemical staining revealed higher expression of inducible nitric oxide synthase (iNOS), VEGF and CD(34) (a marker for microvessel density) in the cardiac tissues after treatment with rosuvastatin compared to control group. The immunostaining for VEGF was positively correlated with microvessel density and iNOS. Overall, the current results provide evidence that the effect of rosuvastatin on myocardial-infarct rats involves induction of angiogenesis.
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt. Sawsan_zaytoon@pharm.suez.edu.eg
Sawsan A
SA
Zaitone
Noha M
NM
Abo-Gresha
D000208:Acute Disease; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004562:Electrocardiography; D005464:Fluorobenzenes / Q000494:pharmacology* / Q000627:therapeutic use; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D007545:Isoproterenol / Q000009:adverse effects*; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017463:Receptors, Complement 3b / Q000378:metabolism; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D016019:Survival Analysis; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D005464:Fluorobenzenes; D011743:Pyrimidines; D017463:Receptors, Complement 3b; D013449:Sulfonamides; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D000068718:Rosuvastatin Calcium; D052247:Nitric Oxide Synthase Type II; D007545:Isoproterenol