U (2012) Cross talk between cardiac myocytes and fibroblasts: frommultiscale investigative approaches to mechanisms and functional consequences

from multiscale investigative approaches to mechanisms and functional conse-quences. Am J Physiol Heart Circ Physiol 303: H1385–H1396, 2012. First published October 12, 2012; doi:10.1152/ajpheart.01167.2011.—The heart is com-prised of a syncytium of cardiac myocytes (CM) and surrounding nonmyocytes, the majority of which are cardiac fibroblasts (CF). CM and CF are highly interspersed in the myocardium with one CM being surrounded by one or more CF. Bidirec-tional cross talk between CM and CF plays important roles in determining cardiac mechanical and electrical function in both normal and diseased hearts. Genetically engineered animal models and in vitro studies have provided evidence that CM and CF can regulate each other’s function. Their cross talk contributes to structural and electrical remodeling in both atria and ventricles and appears to be involved in the pathogenesis of various heart diseases that lead to heart failure and arrhythmia disorders. Mechanisms of CM-CF cross talk, which are not yet fully understood, include release of paracrine factors, direct cell-cell interactions via gap junctions and potentially adherens junctions and nanotubes, and cell interactions with th