Ischemia / Hypoxia On Cardiac Insulin-like Growth Factor 2 Receptor Expression And Regulation Of Experimental Research

Despite considerable advances in the treatment of cardiovascular disease, it remains the leading cause of mortality and morbility in the world. Underlying molecular causes of cardiac dysfunction in most heart diseases are still largely unknown but are expected to result from causal alterations in gene and protein expression. We had already found IGF-2R was highly expressed in the tissues samples from heart failure patients compaired with non-failing hearts. In this article we studied changes of expression of IGF-2R during ventricular remodeling following myocardial infarction. In addition, we studied weather IGF-2R played important roles in the process of ischemia induced apoptosis. All of these studies will contribute to the new strategies of treatment of heart falure.Main contents of this study including:1 Myocardial infarction was created in SD rats by ligation of the left anterior descending coronary artery. The rats were randomly divided into 2 groups:sham group and myocardial infarction (MI) group. Animals were sacrificed at 1day,3day,7days, 2weeks,4weeks,8weeks after operation and the left ventricular tissues were isolated for determination of IGF-2R by enzyme-linked immunosorbent assay (ELISA). Compaired with the sham group, IGF-2R protein was downregulated 1 and 3day after MI, and then returned to normal levels.2 Cultured neonatal rat cardiomyocytes were randomly divided into control group and hypoxia and serum deprivation (H/SD) group. Expression of IGF-2R mRNA was measured by RT-PCR and real time RT-PCR. Level of IGF-2R protein was measured by ELISA.Compared with control group, the expression of IGF-2R mRNA increased significantly (P<0.01) in cardiomyocytes cultured in H/SD condition for 12h and 24h, and IGF-2R protein was upregulated in cardiomyocytes cultured in H/SD condition for 24h(P<0.05). H/SD could induce IGF-2R expression, and IGF-2R may involve in the mechanism of cardiomyocyte damage induced by ischemia.3 Cultured neonatal rat cardiomyocytes were randomly divided into control group, H/SD group, scramble siRNA group and IGF-2R siRNA group.Percentage of apoptotic cells measured by flow cytometry.The results demonstrated that H/SD induced apoptosis of cardiomyocytes, but we did not found that down-regulation of IGF-2R mRNA reduced apotosis in neonatal rat cardiomyocytes cultured in H/SD condition.