Title

The potential clinical application of protein kinase C beta II peptide inhibitor or Gö 6983 in vascular endothelial dysfunction

Document Type

Article

Publication Date

2010

Abstract

Vascular endothelial dysfunction which is associated with increased oxidative stress and decreased endothelial-derived nitric oxide has been considered as a major initial event in various diseases, such as atherosclerosis, diabetes and ischemia/reperfusion (I/R) injury. Previously we found that a broad-spectrum protein kinase C (PKC) inhibitor (i.e., Gö 6983) and a specific PKC beta II peptide inhibitor (PKC ßII-) were cardioprotective in myocardial I/R injury. However, the direct effects of Gö6983 or PKC ßII- on vascular endothelial dysfunction and the related leukocyte-endothelial interactions are still unclear. The leukocyte rolling, adherence and transmigration were estimated by using intravital microscopy in rat mesenteric postcapillary venules. We found that superfusion of NG -nitro-L-arginine-methyl-ester (L-NAME, 50 µM) induced endothelial dysfunction and significantly increased leukocyte-endothelial interactions within a 2 hour period compared to Krebs' buffer control group (P<0.05). By contrast, Gö6983 (25 nM-200 nM) or PKC ßII- (0.1 µM-10 µM) dose-dependently attenuated these interactions induced by L-NAME (P<0.05). Moreover, histological evaluation of Gö 6983 (200 nM) or PKC ßII- (10 µM) superfused mesenteric tissue exhibited significantly less leukocyte adherence and tissue transmigration, as well as significantly less intercellular adhesion molecule-1 expression compared to L-NAME group. Finally, in a rat extracorporeal shock wave lithotripsy model, we demonstrated that PKC ßII- (0.055-0.55 mg/kg) significantly decreased oxidative stress when hydrogen peroxide was measured directly from rat renal veins (P<0.05). In summary, Gö 6983 or PKC ßII- can decrease the proinflammatory responses in vascular endothelium and may provide a potential clinical treatment to prevent vascular endothelial dysfunction.

Publication Title

Current Topics in Pharmacology

Volume

14

Issue

42006

First Page

11

Last Page

24

Comments

This article was published in Current Topics in Pharmacology, Volume 14, Issue 42006, Pages 11-24.

The published version is available at http://www.researchtrends.net/tia/abstract.asp?in=0&vn=14&tid=11&aid=3050&pub=2010&type=3 .

Copyright © 2010 Research Trends.

This document is currently not available here.

COinS