Role of platelet-derived calpain in diabetes-associated vascular diseases.

• Applicant: Privatdozentin Dr. Voahanginirina Randriamboavonjy
• Subject Area: Anatomy and Physiology
• Term: from 2013 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 250828505

Diabetes mellitus is a major risk factor for vascular diseases and is associated with accelerated atherosclerosis and a high rate of arterial thrombotic complications. In addition to endothelial dysfunction platelet hyperactivation is known to contribute to the pathogenesis and progression of the vascular complications of diabetes. Calpains 1 and 2 are expressed in platelets and are involved in physiological platelet activation. However, the inappropriate activation of calpains in diabetes leads to platelet hyperreactivity and enhances calpain secretion. Although the presence of extracellular/circulating calpains has been reported, their link to the development of vascular complications in diabetes is unknown. In the first funding period we could show that calpain carried by PMPs is largely involved in the alteration of vascular integrity and the increased vascular inflammation in diabetes by targeting the glycocalyx and the protease-activated receptor 1 on the endothelial cells. Given that diabetes-associated vascular complications involve a complex interplay between the vascular wall and circulating cells, the aim of this project is to analyze the effect of extracellular calpain on circulating cells such as monocytes and neutrophils. We will specifically assess the role of calpain in the formation of neutrophil extracellular traps as well as in monocyte differentiation and macrophage polarization. Moreover, we will investigate the role of calpain-containing PMPs in the pathogenesis of diabetic microvascular complications such as during diabetic nephropathy.

• DFG Programme: Research Grants