Differential expression of protein kinase C isoforms in coronary arteries of diabetic mice lacking the G-protein Gα11
1 Department of Internal Medicine III, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
2 Dept. of Operative Dentistry, Periodontics and Endodontics, Heinrich-Heine-University, Düsseldorf, Germany
3 Insitute of Anatomy I, University of Cologne, Joseph-Stelzmann Str.9, 50931 Cologne, Germany
4 Max-Planck-Intitute for Heart and Lung research, W.G. Kerckhoff-Institute, Parkstrasse 1, 61231 Bad Nauheim, Germany
Cardiovascular Diabetology 2010, 9:93 doi:10.1186/1475-2840-9-93Published: 29 December 2010
Diabetes mellitus counts as a major risk factor for developing atherosclerosis. The activation of protein kinase C (PKC) is commonly known to take a pivotal part in the pathogenesis of atherosclerosis, though the influence of specific PKC isozymes remains unclear. There is evidence from large clinical trials suggesting excessive neurohumoral stimulation, amongst other pathways leading to PKC activation, as a central mechanism in the pathogenesis of diabetic heart disease. The present study was therefore designed to determine the role of Gq-protein signalling via Gα11 in diabetes for the expression of PKC isozymes in the coronary vessels.
The role of Gα11 in diabetes was examined in knockout mice with global deletion of Gα11 compared to wildtype controls. An experimental type 1-diabetes was induced in both groups by injection of streptozotocin. Expression and localization of the PKC isozymes α, βII, δ, ε, and ζ was examined by quantitative immunohistochemistry.
8 weeks after induction of diabetes a diminished expression of PKC ε was observed in wildtype animals. This alteration was not seen in Gα11 knockout animals, however, these mice showed a diminished expression of PKCζ. Direct comparison of wildtype and knockout control animals revealed a diminished expression of PKC δ and ε in Gα11 knockout animals.
The present study shows that expression of the nPKCs δ and ε in coronary vessels is under control of the g-protein Gα11. The reduced expression of PKC ζ that we observed in coronary arteries from Gα11-knockout mice compared to wildtype controls upon induction of diabetes could reduce apoptosis and promote plaque stability. These findings suggest a mechanism that may in part underlie the therapeutic benefit of RAS inhibition on cardiovascular endpoints in diabetic patients.