BMPR2 mutation in cardiomyocytes impairs insulin-dependent trafficking of CD36

In PAH, insulin resistance is associated with impaired RV function. In mouse model of PAH with mutant BMPR2, we have shown impaired fatty acid oxidation and lipid accumulation in RV cardiomyocytes. We hypothesize that in cardiomyocytes with mutant BMPR2 insulin dependent translocation of CD36, fatty acid transporter molecule, is impaired and may contribute to lipid accumulation. H9C2 cardiomyocytes were stably transfected with empty vector (control) or plasmid containing mutant BMPR2 (mutant). CD36 protein was analyzed by western and confocal microscopy at baseline (BL) and insulin stimulation (IS) at 15 minutes (m), 30m, 1 hour (h), 24h. Key intracellular insulin signaling pathway intermediates analyzed by western. At BL, CD36 was 2fold up in mutant compared to control and increased 2fold in controls at 1h of IS . In mutant, IS lead to 50% increase in CD36 from 15m to 24h. Immunolocalization studies recapitulated these findings. IS increased CD36 in the cytoplasm and plasma membrane (PM) in mutant compar...