Altered Structure And Function In Aging Synemin-Null Murine Heart

Heart disease is the most frequent cause of death in man and becomes more common with age. Cardiomyopathies have been linked to changes in structural proteins, including intermediate filament (IF) proteins. IFs associate with the contractile machinery, intercalated disks and costameres in the heart. Synemin is a large IF protein that mediates the association of desmin with Z-disks and stabilizes intercalated disks. It also acts as an A-kinase anchoring protein (AKAP). In murine skeletal muscle, the absence of synemin causes a mild myopathy. Here, we report that synemin-null cardiac muscle in aging mice shows left ventricular remodeling (elevated diastolic and systolic dimensions) and contractile dysfunction (reduced fractional shortening and ejection fraction), although no change on wall thickness. Aged synm-null mice also show an increase of ~30% in the total body weight. Further experiments to assess the physiology, histopathology and motor performance of aged synm-null mice are in progress. Nevertheless, our data suggest the absence of synemin in aged heart muscle has potentially severe consequences. Supported partially by APS and CONACyT fellowships to KPGP, and by NIH (RO1 AR055928) to RJB