Myocardial expression of survivin, an apoptosis inhibitor, in aging and heart failure. An experimental study in the spontaneously hypertensive rat

Background: Apoptosis plays a major role in the transition to heart failure (HF) in systemic hypertension although the underlying mechanisms are still unclear. The aim of this study was to determine the relationship between apoptosis, left ventricular remodeling, heart failure and the myocyte expression of survivin, an inhibitor of apoptosis. Methods: Spontaneously hypertensive rats (SHR) were used as a model of hypertensive cardiopathy, and Wistar Kyoto Stars rats (WKY) were used as controls. Animals were allowed to survive up to 18 months of age. The animals underwent echocardiography (EDD, ESD and FS were measured). The median section of the heart was processed for in situ end-labeling of DNA fragmentation (TUNEL) and for survivin expression by immunohistochemistry. Results: All SHR presented features of adverse cardiac remodeling. Apoptotic cells were increased in SHR compared with WKY, measured as apoptotic cells per high power field (1.08 +/- 0.43 vs. 0.27 +/- 0.15, P < 0.001), and as apoptotic rate (0.16 +/- 0.06% vs. 0.04 +/- 0.02%, P < 0.001). The incidence of apoptosis showed a positive correlation with unfavorable ventricular remodeling, assessed by echocardiogram. Survivin expression was found in all cases, but the survivin expression index was significantly lower in SHR vs. WKY (43 40% vs. 86 +/- 18%, respectively, P=0.014). Moreover the survivin expression index was inversely correlated with features of adverse remodeling (i.e., Heart Weight, R=-0.79, P < 0.001) and with apoptosis (i.e., apoptotic rate, R=-0.52, P=0.050). Conclusion: Survivin myocardial expression in aging SHR is associated with reduced apoptosis and more favorable cardiac remodeling. Modulation of this pathway may prove beneficial in preventing pressure overload cardiac remodeling and heart failure. (c) 2005 Elsevier Ireland Ltd. All rights reserved.