Differential protein kinase C isoform abundance in ascending aortic aneurysms from patients with bicuspid versus tricuspid aortic valves.
Publication/Presentation Date
9-11-2007
Abstract
BACKGROUND: It is recognized that different events contribute to the initiation of ascending thoracic aortic aneurysms (ATAAs) in patients with bicuspid aortic valves (BAV) versus patients with tricuspid aortic valves (TAV), but the molecular signaling pathways driving aneurysm formation remain unclear. Protein kinase C (PKC) is a superfamily of kinases which differentially mediate signaling events that lead to altered gene expression and cellular function, and may regulate downstream mediators of vascular remodeling. The present study tested the hypothesis that ATAA development in patients with BAV versus TAV proceeds by independent signaling pathways involving differential PKC signaling.
METHODS AND RESULTS: ATAA samples were collected from BAV (n=57) and TAV (n=55) patients and assessed for 10 different PKC isoforms by immunoblotting. Results were expressed as a percent change in abundance (mean+/-SEM) from a nonaneurysmal control group (100%, n=21). Correlation analysis was performed, and relationships between PKC and matrix metalloproteinase abundance were reported. In the BAV group, classic and novel PKC isoforms (PKC-alpha, betaI, gamma, epsilon, theta) were increased, whereas PKC-eta and atypical PKC-zeta were decreased. In the TAV group, classic and novel isoforms were decreased and atypical PKC-zeta was elevated. Positive correlations between PKC and matrix metalloproteinase abundance were identified.
CONCLUSIONS: Differential PKC isoform abundance was observed in ATAA samples from patients with BAV versus TAV, suggesting independent molecular signaling pathways may be operative. Induction of independent transcriptional programs may result and may provide a mechanistic foundation for developing selective diagnostic/therapeutic strategies for patients with ATAAs secondary to BAV or TAV.
Volume
116
Issue
11 Suppl
First Page
144
Last Page
149
ISSN
1524-4539
Published In/Presented At
Jones, J. A., Stroud, R. E., Kaplan, B. S., Leone, A. M., Bavaria, J. E., Gorman, J. H., 3rd, Gorman, R. C., & Ikonomidis, J. S. (2007). Differential protein kinase C isoform abundance in ascending aortic aneurysms from patients with bicuspid versus tricuspid aortic valves. Circulation, 116(11 Suppl), I144–I149. https://doi.org/10.1161/CIRCULATIONAHA.106.681361
Disciplines
Medicine and Health Sciences
PubMedID
17846295
Department(s)
Department of Surgery
Document Type
Article