Marica Bakovic
University of Guelph, Canada
Title: The role of membrane phospholipids in development of male-specific cardiac hypertrophy and hypertension
Biography
Biography: Marica Bakovic
Abstract
Phospholipids play an indispensable role in heart function via their structural and metabolic roles, and serve as a barrier that protects the intracellular cell environment. The first evidence of mammalian heart dysfunction in relation to deregulated phospholipid synthesis by the CDP-ethanolamine Kennedy pathway came from our recent study with CTP: phosphoethanolamine cytidylyltransferase (Pcyt2) heterozygous mice ETKO. ETKO mice of both genders have reduced phosphatydylethnolamine (PE) synthesis and turnover, accumulate plasma and tissue triglycerides and develop insulin resistance. However, only ETKO males develop age-related cardiac hypertrophy and hypertension. The underlying mechanism for the male specific dysfunction was identified in the accumulation of arachidonic acid and other n-6 elongation/desaturation pathway intermediates in the male heart membranes and reduced circulating testosterone levels. There is a clear sexual dimorphism in the heart phospholipids and the sex-related differences expand to the heart neutral lipids but not cardiolipin. Dysfunctional Pcyt2 gene (reduced PE synthesis and turnover) causes insulin resistance in both males and females, however specifically perturbs membrane metabolism protecting the female heart and causing the male-specific diabetic cardiomyopathy. We explore the nature of those differences to show what role Pcyt2 plays in cardiac cell function, signaling, and gene expression and how they contribute the male-specific hypertension and heart pathology.