Protein kinase C in enhanced vascular tone in diabetes mellitus

作者：Kizub Igor V^*; Klymenko Kateryna I; Soloviev Anatoly I

来源：International Journal of Cardiology, 2014, 174(2): 230-242.

DOI：10.1016/j.ijcard.2014.04.117

• Ca2+ sensitization
• Diabetes
• Endothelium
• Hyperglycemia
• Protein kinase C
• Vascular tone

Diabetesmellitus (DM) is a complex syndrome which leads to multiple dysfunctions including vascular disorders. Hyperglycemia is considered to be a key factor responsible for the development of diabetic vascular complications and can mediate their adverse effects through multiple pathways. One of those mechanisms is the activation of protein kinase C (PKC). This important regulatory enzyme is involved in a signal transduction of several vascular functions including vascular smooth muscle contractility. Many studies have shown that hyperglycemia in DM results in oxidative stress. Overproduction of reactive oxygen species (ROS) by different oxidases and the mitochondrial electron transport chain (ETC), advanced glycation end products, polyol pathway flux, and hyperglicemia-induced rising in diacylglycerol (DAG) contribute to the activation of PKC. Activation of endothelial PKC in DM leads to endothelium-dependent vasodilator dysfunction. The main manifestations of this are inhibition of vasodilatation mediated by nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and prostacyclin, and activation of vasoconstriction mediated by endothelin-1 (ET-1), prostaglandin E-2 (PGE(2)) and thromboxane A(2) (TXA(2)). Activated PKC in DM also increases vascular endothelial growth factor (VEGF) expression and activates NADPH oxidases leading to raised ROS production. On the other hand, PKC in DM is involved in enhancement of vascular contractility in an endothelium-independent manner by inactivation of K+ channels and Ca2+ sensitization of myofilaments in vascular smooth muscle cells. This shows that PKC is a potential therapeutic target for treating vascular diabetic complications.

• 出版日期2014-6-15