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(Circulation. 2007;116:I-144 – I-149.)
© 2007 American Heart Association, Inc.

Surgery for Aortic Disease

Differential Protein Kinase C Isoform Abundance in Ascending Aortic Aneurysms From Patients With Bicuspid Versus Tricuspid Aortic Valves

Jeffrey A. Jones, PhD; Robert E. Stroud, MS; Brooke S. Kaplan, BS; Allyson M. Leone, BS; Joseph E. Bavaria, MD; Joseph H. Gorman, III, MD; Robert C. Gorman, MD; John S. Ikonomidis, MD, PhD

From the Cardiothoracic Surgical Research (J.A.J., R.E.S., B.S.K., A.M.L., J.S.I.), Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston; and Division of Cardiothoracic Surgery (J.E.B., J.H.G., R.C.G.), University of Pennsylvania, Philadelphia.

Correspondence to John S. Ikonomidis, MD, PhD, Associate Professor of Surgery, Division of Cardiothoracic Surgery, Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas St, Suite 409 CSB, Charleston, SC 29425. E-mail ikonomij{at}musc.edu

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-, ßI, , , ) were increased, whereas PKC- and atypical PKC- were decreased. In the TAV group, classic and novel isoforms were decreased and atypical PKC- 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.

Key Words: valves • aneurysm • aorta • PKC • metalloproteinases