Endothelial protein kinase C isoform identity and differential activity of PKCzeta in an athero-susceptible region of porcine aorta.
Endothelial protein kinase C (PKC) signaling was investigated in different regions of normal porcine aorta. The locations map to differential atherosclerotic susceptibility and correlate with sites of disturbed (DF) or undisturbed (UF) local flow profiles. Endothelial lysates were isolated from the inner curvature of the aortic arch (DF; athero-susceptible) and a nearby UF region of the descending thoracic aorta (UF; athero-protected), and in some experiments a distant athero-protected UF site, the common carotid artery. Total endothelial PKC activity in the DF regions was 145% to 240% of that in both UF locations (P<0.05), whereas the UF regions were not significantly different from each other. PKC protein isoforms alpha, beta, epsilon, iota, lambda, and zeta were expressed in similar proportions in both aortic regions, suggesting that differences of kinase activity were not directly attributable to expression levels. Inhibition of members of the "conventional" and "novel" PKC families had no differential effect on regional kinase activity. However, inhibition of PKCzeta, a member of the "atypical" PKC family, reduced the DF lysate kinase activity to that of UF levels (NS P=0.35). Differential phosphorylation of PKCzeta Thr410 and Thr560, along with increased levels of PKCzeta degradation products in UF endothelial lysates, suggested posttranslational modification of PKCzeta as the basis for site-specific differences in vivo. Steady-state regional heterogeneity of an important family of regulatory proteins in intact arterial endothelium in vivo may link localized athero-susceptibility and the associated hemodynamic environment.
Magid
Richard
R
Institute for Medicine and Engineering, Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104-6383, USA. rmagid@alum.mit.edu
Davies
Peter F
PF
D000818:Animals; D001011:Aorta / Q000201:enzymology*; D001161:Arteriosclerosis / Q000188:drug therapy / Q000209:etiology*; D004198:Disease Susceptibility; D004730:Endothelium, Vascular / Q000201:enzymology*; D006439:Hemodynamics; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D013552:Swine; D000099221:Protein Kinase C zeta
D007527:Isoenzymes; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta