Protein kinase C participation in the mechanisms of vascular tone disturbance upon diabetes mellitus. Part 4

Abstract

Diabetes mellitus (DM) is acompaining by vascular tone desorders development. Regulatory enzyme protein kinase C (PKC) is involved in mechanisms of these desorders development. Numerous studies have demonstrated that contractile responces of vascular smooth muscle are enchansed in DM and endothelium-independent PKC-mediated mechanisms are involved in this process. Such mechanisms are PKC-mediated inhibition of Ca2+ activated K+ channels (BKCa) in vascular smooth muscle cells (SMCs) and SMCs myophilaments Ca2+ sensitization. PKC is a potential therapeutic target for treating vascular diabetic complications. A few compounds among PKC inhibitors already exist, such as ruboxistaurin, indolylmaleimide and its derivatives. Recently discovered method of RNA-interference (RNAi) is an essential gene-silencing tool and can also be used for PKC inhibition and DMassociated vascular complicaions elimination.

Circulating in the blood desquamated endotheliocytes at the diabetic nephropathy

“…In conditions of hyperglycemia, glucose self-oxidizes to diacylglycerol, a powerful stimulator of protein kinase C activity, which is involved in the activation of inflammatory and profibrotic cytokines, growth factors, With the subsequent stimulation of secretion of vasoactive prostanoids, which promotes the development of nephrosclerosis [10,11]. In recent years, special attention has been paid to the pathogenetic role of endothelial dysfunction (ED) in the development of major complications of diabetes [12].…”