Abstract 315: Stromal Cell-derived Factor 1 Protects From Diabetic Cardiomyopathy

Abstract

We have demonstrated that stromal cell-derived factor 1(SDF-1) protects against palmitate-induced cardiac apoptosis, which is mediated by NOX-activated nitrosative damage and endoplasmic reticulum stress, via CXCR7, to activate AMPK/p38 MAPK-mediated IL-6 generation (Diabetes 62:2545-2558, 2013). Whether SDF-1 prevents diabetic cardiomyopathy has not been addressed. Here we evaluated the preventive effects of SDF-1 from diabetic cardiomyopathy in a high fat diet plus streptozotocin (HFD/STZ)-induced type 2 diabetic model in C57BL/6J mice. After 1 month on HFD, cardiac function was assayed by echocardiography, and then HFD-fed mice were injected with one low dose STZ (100mg/kg body weight, ip). Five days after STZ injection, mice with blood glucose levels ≥250 mg/dl were defined as diabetic. In parallel, the age-matched normal diet-fed mice injected with a same volume of citrate buffer (pH4.5) were used as control. After onset of diabetes, the mice were maintained on HFD or normal diet for another 4 months with or without SDF-1 treatment. Then cardiac function was assayed again, and the mice were sacrificed and cardiac tissue collected for cardiomyopathic index assay. We found that 1 month HFD feeding induced a significant insulin resistance without effect on cardiac function, but continued HFD feeding after STZ injection significantly impaired cardiac function, which were accompanied by increased insulin resistance and blood glucose, as well as blood insulin, triglyceride and cholesterol levels. Treatment with SDF-1 dose-dependently prevented diabetes-induced cardiac dysfunction but without significant effects on the above mentioned other pathophysiological parameters. These results indicate that SDF-1 possibly prevents diabetic cardiomyopathy via a direct cardiomyocyte action, which needs to be further defined in future study.