Thrombomodulin is Upregulated in Cardiomyocytes During Cardiac Hypertrophy and Prevents the Progression of Contractile Dysfunction

Background Cardiac hypertrophy is a common response to pressure overload and leads to left ventricular (LV) dysfunction Thrombomodulin (TM) an endothelial anticoagulant protein was found to have direct effects on cellular proliferation and inflammation We examined the TM expression in cardiomyocytes during cardiac hypertrophy and investigated its physiological significance Methods and Results TM expression was evaluated in cardiomyocytes from hearts of mice that under went transverse aortic constriction (TAC) The effects of recombinant TM protein on cardiomyocytes apoptosis and related signaling pathways were examined Recombinant TM protein was administered continuously in mice that underwent TAC and serial LV function was determined There was significant TM expression in cardiomyocytes during cardiac hypertrophy elicited by TAC in mice TM treatment de creased doxorubicin induced apoptosis of cardiomyocytes and increased the Bcl 2/Bax ratio It also in creased cardiomyocytes hypertrophy expression of atrial natriuretic peptide and significantly activated the extracellular signal-regulated kinase 1/2 (ERK1/2) and the phosphatidylinositol 3 kinase (PI3 K)/protein kinase B (Akt) signaling pathways in cardiomyocytes Continuous TM supply after TAC prevented the progression of LV contractile dysfunction in mice Conclusions TM treatment decreased cardiomyocyte apoptosis and maintained LV contractile function in response to pressure overload (J Cardiac Fail 2010 16 980-990)