Implications of myocardial matrix remodeling by adipokines in obesity-related heart failure

Abstract

Owing to the increased incidence of obesity and its association with heart failure, there is now great interest in elucidating the underlying molecular mechanisms linking these pathologies. Since the discovery of adipose-derived hormones and cytokines, their important regulatory role in myocardial function has emerged. The events that these adipokines can regulate include alterations in myocardial metabolism, cardiomyocyte hypertrophy, cell death, and structure and composition of the extracellular matrix. Here, we focus on the last of these and review current research demonstrating an important role for adipokines, with particular emphasis on leptin and adiponectin, in regulating matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, and collagens. From this, it is clear that adipokines are capable of contributing to remodeling of the myocardial extracellular matrix, and the altered adipokine profiles observed in obese individuals may be important in the pathogenesis of heart failure. The feasibility of adipokine manipulation as a potential therapeutic treatment in preventing maladaptive cardiac remodeling is also discussed.