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Circulation Research. 2005
Published online before print July 28, 2005, doi: 10.1161/01.RES.0000179767.37838.60
A more recent version of this article appeared on September 2, 2005
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Submitted on February 14, 2005
Revised on July 20, 2005
Accepted on July 20, 2005

Endothelial Protein Kinase C Isoform Identity and Differential Activity of PKC{zeta} in an Athero-Susceptible Region of Porcine Aorta

Richard Magid and Peter F. Davies *

From the Institute for Medicine and Engineering (R.M., P.F.D.) and Departments of Pathology and Laboratory Medicine (P.F.D.) and Bioengineering (R.M., P.F.D.), University of Pennsylvania, Philadelphia.

* To whom correspondence should be addressed. E-mail: pfd{at}pobox.upenn.edu.

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 PKC{zeta}, 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 PKC{zeta} Thr410 and Thr560, along with increased levels of PKC{zeta} degradation products in UF endothelial lysates, suggested posttranslational modification of PKC{zeta} 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.
Key words: endothelial phenotypic heterogeneity • site-specific PKC activity • flow disturbance • hemodynamics




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