Cardioprotective Mechanisms of Exenatide in Isoprenaline-induced Myocardial Infarction: Novel Effects on Myocardial α-Estrogen Receptor Expression and IGF-1/IGF-2 System.

Myocardial infarction (MI) is one of the main causes of morbidity and mortality in diabetic patients. The antidiabetic glucagon-like polypeptide-1 receptor (GLP-1R) agonists, such as exenatide, proved to confer cardioprotection; however, their exact mechanisms are not fully elucidated. Although the cardioprotective effect of α-estrogen receptor (ERα) activation is well established, its involvement in exenatide-induced cardioprotection has never been investigated. Moreover, modulation of insulin-like growth factor-1/2 (IGF-1/IGF-2) system by exenatide, and the consequent effect on cardiomyocyte apoptosis, is yet to be established. Current study aimed to investigate the cardioprotective potential of exenatide versus the standard cardioprotective agent, 17ß-estradiol, against isoprenaline (ISO)-induced MI in rats. MI-insulted group showed electrocardiographic abnormalities, elevated serum cardiac markers, higher serum IGF-2 level along with histopathological abnormalities. Treatment with exenatide and/or 17ß-estradiol, commenced 8 weeks before ISO insult, ameliorated these anomalies with maximum cardioprotection achieved with combined treatment. This was associated with upregulation of both ERα and IGF-1R, and downregulation of IGF-2R in left ventricles. Inhibition of ERs in Langendorff preparations confirmed their involvement in mediating exenatide-induced cardioprotective effect. Current study showed that the GLP-1R agonist exenatide exerted cardioprotection associated with upregulation of ERα and modulation of IGF-1/IGF-2 signaling in favor of antiapoptosis.

Evening primrose oil ameliorates platelet aggregation and improves cardiac recovery in myocardial-infarct hypercholesterolemic rats.

Omega-6 polyunsaturated fatty acids (n-6 PUFA) are well known for their role in cardiovascular disease (CVD). We proposed that Evening prime rose oil (EPO) can improve the outcome of a heart with myocardial infarction (MI) in the presence of diet-induced hyperaggregability. This study was designed to examine its cholesterol lowering, antithrombotic and anti-inflammatory effects. High fat diet was administered for 4 weeks then MI was induced by isoproterenol (85 mg/kg/s.c./24 h). Treatment with EPO (5 or 10 gm/kg/day) for 6 weeks improved the electrocardiographic pattern, serum lipid profile, cardiac biomarkers as well as Platelet aggregation percent. We reported decreased serum level of TNF-α, IL-6 and COX-2 with attenuation of TNF-α and TGF-ß in the cardiac homogenate. Moreover, histopathology revealed marked amelioration. Finally, we provide evidence that EPO improve cardiac recovery in hypercholesterolemic myocardial infarct rats. These effects are attributed to direct hypocholesterolemic effect and indirect effect on the synthesis of eicosanoids (prostaglandins, cytokines).

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.