The role of calpain in diabetes-associated platelet hyperactivation.

Diabetes mellitus is a major risk factor for vascular diseases and is associated with accelerated atherosclerosis and a high rate of arterial thrombotic complications. A number of studies support the concept that platelets contribute to the pathogenesis and progression of the vascular complications of diabetes. µ-Calpain, a non-lysosomal, Ca(2+)-dependent cysteine protease, is expressed in platelets and is involved in physiological platelet activation. However, the inappropriate activation of calpain alters platelet function, partially degrades a spectrum of proteins and results in hyperaggregability. Changes in the activity of calpain in different cells involved in diabetes-related pathways, or the polymorphism of calpain genes have been associated with the development of type 2 diabetes but their relevance to the diabetes-related vascular complications is not really clear. This review will give an overview of the role of calpain in diabetes and analyze the role of calpain in platelet activation and the changes occurring during the onset of diabetes. Finally, we will discuss future therapeutic possibilities for the improvement of diabetes-associated vascular diseases.