REGIONAL SERCA2a PROTEIN EXPRESSION IN THE POST-MI MODEL OF HEART FAILURE:

Objective: The downregulation of calcium handling proteins is a major contributor to myocardial dysfunction in post-MI heart failure. SERCA2a is a key Ca2+ exporter and its reduction leads to the Ca2+ depletion observed in models of post-MI heart failure. In our study we quantified the regional expression of SERCA2a from failing myocardium. Methods: Using a post-MI ovine model of heart failure three groups were created; virgin (n=2), control (n=4), and mechanically assisted (n=2). Six weeks post infarction a terminal study was performed and tissue harvested for protein analysis using Western blot with phosphoimager quantification. Results: The virgin group had normal and uniform levels of SERCA2a expression throughout the myocardium. The control group and LVAD supported group showed regional differences in SERCA2a levels based on proximity to the area of infarction. In contrast to the LVAD group, the control group SERCA2a expression was significantly depressed with 20–70 % reduction. Conclusions: Our study demonstrated that (1) regionality of SERCA2a protein expression exists in heart failure; (2) this regionality correlates with the degree of myocyte injury; and (3) mechanical unloading of the failing heart restores myocardial expression of SERCA2a.Figure