Abstract 3543: Profiling of Protein Kinase C Isoforms in Ascending Aortic Aneurysms In Patients with Marfan Syndrome
Objective: Marfan syndrome (MFS), an inherited defect in the extracellular matrix protein fibrillin, is associated with an increased incidence of ascending thoracic aortic aneurysms (ATAAs) which may occur through different mechanisms than ATAAs resulting from other causes. Protein kinase C (PKC) is an intracellular signaling enzyme family characterized into three subclasses (conventional, novel, and atypical) based on co-factor requirements for activation. Recent evidence has linked changes in PKC expression and activity to aneurysm formation. This study tested the hypothesis that differential PKC isoform profiles are present in ATAAs in MFS compared to degenerative ATAAs in patients with tricuspid aortic valves (TAV).
Methods: A comprehensive profile of PKC isoforms was measured by quantitative immuno-blotting in surgical ATAA specimens from 8 patients with MFS, 55 patients with TAV and a reference control group (n=21) of normal ascending aortic specimens. Results (mean ± SEM) are expressed as a percentage of reference control values set at 100%.
Results: Specific patterns of PKC isoform expression occurred in the two ATAA groups. Specifically, in the TAV group a decrease was observed in conventional PKCs -β-II, -γ, and in novel PKC -ϵ, while an increase was observed in atypical PKC-ζ. In contrast, in the MFS group, decreases in novel PKCs -δ, -ϵ, -𝛉 and atypical PKC -ι were demonstrated.
Conclusions: This unique study reveals differential PKC isoform induction in ATAA patients with MFS versus TAV. These results provide a mechanistic foundation for the development of novel diagnostic/therapeutic strategies specific for these subclasses of ATAA.