Pathologic Cardiac Hypertrophy, but not Physiologic Cardiac Growth, Induces O‐GlcNAc Signaling

Background Pathologic cardiac hypertrophy is a frequent manifestation in heart disease. Pro‐adaptive cardiac hypertrophy occurs in endurance training, yet, we do not understand the mechanisms. Because O‐linked N‐acetylglucosamine (O‐GlcNAc) is a glucose‐derived post‐translational modification important in the cardiovascular system, we hypothesized that it figured prominently in pressure‐overload, but not exercise‐induced, cardiac hypertrophy. Methods and Results We subjected wild‐type mice to transverse aortic constriction (TAC) to induce pathologic cardiac hypertrophy and were evaluated through four weeks via echocardiography. To induce physiologic cardiac growth, we subjected wild‐type mice to a rigorous, four‐week swim protocol. Like the TAC model, swimming significantly (p<0.05) increased cardiac mass and cardiomyocyte cross‐sectional area (p<0.05) compared to their non‐swum littermates. O‐GlcNAc levels significantly (p<0.05) increased during pathologic hypertrophy but remained unchanged during physiological hypertrophy. Conclusions O‐GlcNAc signaling plays an integral role in the response to pressure overload‐induced hypertrophy. We hypothesize that enhanced O‐GlcNAc signaling may represent at least one molecular explanation for the differential responses of pathologic versus physiologic hypertrophy. Funding: NIH, AHA.