Abstract 369: Annexin A5 is a Marker of Cardiomyocyte Apoptosis and Systolic Dysfunction in Heart Failure of Hypertensive Origin
Increased cardiomyocyte apoptosis has been reported in hypertensive patients with left ventricular hypertrophy that develop heart failure (HF). On the other hand, apoptosis leads to Annexin A5 (AnxA5) secretion from cardiomyocytes. We thus want to evaluate whether AnxA5 is a good marker of cardiac apoptosis and dysfunction in HF hypertensives. To perform this study, transvenous endomyocardial biopsies and plasma from peripheral and coronary blood were obtained in 9 hypertensives with normal cardiac function (group 1), and in 23 hypertensives with clinical manifestations of HF (group 2). Cardiomyocyte apoptosis was quantified by TUNEL, and confirmed by active caspase-3 immunocytochemistry and PARP cleavage. Myocardial AnxA5 expression and localization was measured by Western blot and immunocytochemistry respectively. AnxA5 concentration in peripheral and coronary plasma was measured by ELISA. Myocardial AnxA5 expression was higher (P<0.01) in group 2 than in group 1. Immunocytochemical analysis revealed that in HF patients, AnxA5 increase was located in cardiomyocytes, mainly in sarcolemma and intercalated disks. AnxA5 concentration in peripheral and coronary plasma was higher (P<0.001) in group 2 than in group 1. In group 2, AnxA5 concentration in coronary plasma was higher (P<0.001) than in peripheral plasma. AnxA5 in peripheral plasma directly correlated with AnxA5 in coronary plasma (r=0.850, P<0.001), and with AnxA5 in myocardium (r=0.434, P<0.05). Cardiomyocyte apoptosis was higher (P<0.01) in group 2 than in group 1, and it was directly correlated with AnxA5 expression in myocardium (r=483, P<0.05), and in peripheral plasma (r=0.469, P<0.01). For a cut point of 17.7 ng/mL, AnxA5 in peripheral plasma had a sensitivity of 71,4% and a specificity of 87% for detecting apoptosis levels typical of HF and an odd risk=16.7 (CI 95%, 3.6–77.7). Finally, AnxA5 expression in myocardium and peripheral plasma was inversely correlated with the ejection fraction (myocardial AnxA5: r=0.457, P<0.05; peripheral plasma AnxA5 r=0.372 P<0.05). In conclusion, these data demonstrate that AnxA5 is released from the heart into the bloodstream in patients with HF, and that it is associated with cardiomyocyte apoptosis and systolic dysfunction.