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

Author:

Chacar StephanieORCID,Abdi AbdulhamidORCID,Almansoori KhalifaORCID,Alshamsi JawaherORCID,Al Hageh CynthiaORCID,Zalloua PierreORCID,Khraibi Ali A.ORCID,Holt Stephen G.ORCID,Nader MoniORCID

Abstract

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 vessels. 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 (activation/oxidation). The efficiency of CaMKII inhibitors is currently being tested in animal models, with a focus on the genetic pathways involved in the regulation of CaMKII expression (microRNAs and single nucleotide polymorphisms). Interestingly, studies highlight an interaction between the anti-diabetic drugs and CaMKII expression/activity which requires further investigation. Together, the studies reviewed herein may guide pharmacological approaches to improve health-related outcomes in patients with diabetes.

Funder

Khalifa University, United Arab Emirates

Publisher

Springer Science and Business Media LLC

Subject

Endocrinology,Endocrinology, Diabetes and Metabolism

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