Personalizing biomarker strategies in heart failure with galectin-3

Abstract

Heart failure is a leading cause of death and disability. Galectin-3 expression is associated with myocardial fibrosis; recombinant galectin-3 can induce myocardial fibrosis in experimental animals. However, the fact that endogenous galectin-3 is causative of myocardial fibrosis is yet to be firmly established. Nevertheless, the important discovery that N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a naturally occurring anti-inflammatory and antifibrotic peptide, inhibits galectin-3 expression, which prevents cardiac remodeling and dysfunction, provides impetus for translational research into anti-galectin therapy. The lack of a close relationship between galectin-3 and brain natriuretic peptide creates the possibility of a complimentary role. Thus, whilst brain natriuretic peptide is a useful biomarker for diagnosing heart failure, galectin-3 appears to be a culprit biomarker that mediates the development of heart failure, raising the possibility that specific anti-galectin therapy may halt the development of heart failure. Furthermore, data are beginning to emerge supporting the hypothesis that galectin-3 is crucial in the angiotensin–aldosterone pathway leading to salt and water retention, a key mechanism which can result in the development of heart failure. Thus, one might expect patients with heart failure and raised levels of galectin-3 to benefit from aldosterone antagonist therapy. Numerous clinical trials have already established the role of galectin-3 in predicting response to heart failure management, in particular how high levels of galectin-3 predicts mortality. A recent post hoc analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) suggested that patients with relatively low galectin-3 levels (<19 ng/ml) are most likely to benefit from statin therapy. This generated an important hypothesis that deserves further study.