Cellular Basis for Heart Failure

The failing heart manifests significant alterations at a cellular level both in cardiac myocytes and in nonmyocyte cells. Here, we review the main cardiomyocyte alterations that contribute to the pathogenesis of heart failure. A key cardiac manifestation of heart failure is contractile dysfunction, which involves changes in excitation-contraction coupling (particularly calcium handling) and sarcomeric function. The main mechanisms that contribute to this abnormality are discussed. Global alterations within cardiomyocytes that also impact on contractile function and cell viability include changes in redox homeostasis and signaling, cellular stress responses, and macromolecular and protein turnover. These global processes interact with each other and have complex effects on the remodeling process (e.g., redox homeostasis and signaling modulate excitation-contraction coupling). Other cell types within the heart also affect the cardiomyocyte phenotype in the failing heart. Finally, noncoding mRNAs such as microRNAs and long noncoding mRNAs are emerging as key regulators of gene expression and translation during heart failure. An understanding of these fundamental molecular and cellular mechanisms may lead to new therapies for heart failure.