0243: Effect of diabetes on cardiac microparticles release following coronary artery ligation

Abstract

Microparticles (MPs) are 0.1-1 μm membrane-shed vesicles released following cell activation/apoptosis. Little is known about how MPs release in the ischemic myocardium. We aimed to evaluate the cardiac MPs release after myocardial infarction (MI) in diabetic mice. C57BL/6 mice were treated by streptozotocin and coronary artery ligation was performed during 6 hours to 72 hours at the end of 12 weeks' hyperglycemia. MPs from both sham and ischemic myocardial muscles obtained from control and diabetic mice were isolated after sequential centrifugation. Flow cytometry analysis quantified the peak formation of phosphatidylserine+MPs (PS+MPs) using annexin V. Plasma MPs were also analyzed and compared to those observed in cardiac tissues. A GFP-α-actin transgenic mouse model was used to characterize the GFP packing in cardiac MPs. PS-rich MPs were measurable in the mouse heart. In control mice, cardiac MP level increased till 15 hours after ligation, then returned to a basal level 72 hours later. In diabetic mice, myocardial MP increase following MI was delayed and more transient than in control mice after onset of coronary arteries ligation. Cardiac MP levels showed no significant difference between diabetic mice and control mice. Cardiac MPs were also isolated from GFP-α-actin transgenic mice heart. 39% PS+MPs showed GFP+, demonstrating that they were originating from cardiomyocytes. The platelet-free plasma of control mice contained extremely low levels of PS+MPs. Plasma MP levels were higher in diabetic mice than in control mice. This study reports for the first time that coronary artery ligation transiently increases local MPs generation in mouse heart, in particular those originating from cardiomyocytes. MPs levels were increased in both plasma and heart of diabetic mice, where they could contribute to disease progression.