Journal
CIRCULATION RESEARCH
Volume 97, Issue 5, Pages 443-449Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.RES.0000179767.37838.60
Keywords
endothelial phenotypic heterogeneity; site-specific PKC activity; flow disturbance; hemodynamics
Funding
- NHLBI NIH HHS [HL07954, T32 HL007954, P01 HL062250, R37 HL036049-13, HL70128, HL80867, P01 HL062250-11A17993, T32 HL007954-05, P50 HL070128, HL62250, F32 HL080867-01, HL36049, R37 HL036049, F32 HL080867] Funding Source: Medline
Ask authors/readers for more resources
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, nu, 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available