Abstract 3457: Differential Protein Kinase C Isoform Abundance in Ascending Aortic Aneurysms from Patients with Bicuspid versus Tricuspid Aortic Valves
Objective: While it is recognized that different natural histories and pathophysiological events lead to ascending thoracic aortic aneurysms (ATAAs) in patients with bicuspid (BAV) versus tricuspid (TAV) aortic valves, the molecular signaling pathways which may drive ATAA formation in these conditions remain unclear. Protein kinase C (PKC) is an isoenzyme family of serine/threonine kinases, stratified to three classifications (conventional, novel, atypical) based on specific co-factor requirements for activation. PKC isoform activation differentially mediates signal transduction events that alter gene expression and cellular function. This study tested the hypothesis that independent signaling pathways involving differential PKC signaling contribute to the unique etiologies of the ATAA valve groups.
Methods: ATAA samples were collected from BAV (n=57) and TAV (n=55) patients at surgical resection. PKC isoform abundance was assessed by quantitative immunoblotting and compared to non-aneurysmal aortic samples collected from reference control patients (n=21). Results (mean ± SEM) were expressed as a percent change from the reference control group.
Results: Differential abundance of several PKC isoforms was identified in each ATAA subgroup. In the BAV group, elevation of conventional and novel isoforms was observed. Whereas in the TAV group, the conventional and novel isoforms were decreased from control and an atypical isoform was elevated.
Conclusions: This study identified a divergence in PKC isoform abundance in samples from ATAA patients with BAV versus TAV, and suggests that independent molecular signaling pathways may be operative in each ATAA etiology. These differences in the molecular signaling likely lead to the induction of independent transcriptional programs, and may thus provide a mechanistic foundation for developing selective diagnostic/therapeutic strategies for patients with aneurysmal disease secondary to BAV or TAV.