Contributions of cardiomyocyte-cardiac fibroblast-immune cell interactions in heart failure development.

The heart contains various types of cells, including cardiomyocytes, cardiac fibroblasts, many kinds of immune cells and vascular cells. Initial studies mainly focused on cardiomyocytes, which directly reflect the contractile function of the heart. Recently, pivotal functions of cardiac fibroblasts have been revealed in the maintenance of cardiac function, physiological cardiac remodeling after heart stress and pathological remodeling using genetically engineered mouse models, like the fibroblast-specific gene knockout mouse, bone marrow transplantation and immune cell-specific gene knockout. Moreover, chronic inflammation is considered to be a basic pathological mechanism that underlies various diseases, including heart failure. In the development of heart failure, the contributions of immune cells like T lymphocytes and monocyte/macrophage lineage cells have been also reported. Immune cells have diverse and multiple functions in regulating both pro-inflammatory effects and the resolution of heart failure. On the one hand, immune cells have protective effects to compensate for and overcome heart stresses. On the other hand, they also contribute to sustained inflammation and result in the development of heart failure. These observations prompted a shift in the heart-related studies to include the complex communications between cardiomyocytes and other kinds of cardiac cells, including inflammatory cells residing in or recruited to the heart. This review will summarize the current knowledge regarding cell-cell interactions during cardiac remodeling and the development of heart failure. We will especially focus on the interactions among cardiomyocytes, cardiac fibroblasts and immune cells.