Role of CaMKII in diabetes induced vascular injury and its interaction with anti-diabetes therapy

AbstractDiabetes mellitus is a metabolic disorder denoted by chronic hyperglycemia that drives maladaptive structural changes and functional damage to the vasculature. Attenuation of this pathological remodeling of blood vessels remains an unmet target owing to paucity of information on the metabolic signatures of this process. Ca2+/calmodulin-dependent kinase II (CaMKII) is expressed in the vasculature and is implicated in the control of blood vessels homeostasis. Recently, CaMKII has attracted a special attention in view of its chronic upregulated activity in diabetic tissues, yet its role in the diabetic vasculature remains under investigation.This review highlights the physiological and pathological actions of CaMKII in the  diabetic vasculature, with focus on the control of the dialogue between endothelial (EC) and vascular smooth muscle cells (VSMC). Activation of CaMKII enhances EC and VSMC proliferation and migration, and increases the production of extracellular matrix which leads to maladaptive remodeling of ve ssels. This is manifested by activation of genes/proteins implicated in the control of the cell cycle, cytoskeleton organization, proliferation, migration, and inflammation. Endothelial dysfunction is paralleled by impaired nitric oxide signaling, which is also influenced by CaMKII signaling (activa tion/oxidation). The efficiency of CaMKII inhibitors is currently being tested in animal models, with a focus on the genetic pathways involved in the regulation...
Source: Reviews in Endocrine and Metabolic Disorders - Category: Endocrinology Source Type: research