Origins of Cardiac Fibroblasts

Abstract: Cardiac fibroblasts play a critical role in maintenance of normal cardiac function. They are indispens-able for damage control and tissue remodeling on myocardial injury and principal mediators of pathological cardiac remodeling and fibrosis. Despite their manyfold functions, cardiac fibroblasts remain poorly character-ized in molecular terms. Evidence is evolving that cardiac fibroblasts are a heterogeneous population and likely derive from various distinct tissue niches in health and disease. Here, we review our emerging understanding of where cardiac fibroblasts come from, as well as how we can possibly use this knowledge to develop novel therapies for cardiac fibrosis. (Circ Res. 2010;107:1304-1312.) Key Words: fibroblasts fibrosis fate mapping Physiological cardiac function and chronic heart failure arecontrolled by complex interactions of the myocytes, extracellular matrix (ECM), and nonmyocyte cellular compo-nents, including the cardiac fibroblasts.1,2 With their various functions, cardiac fibroblasts are at the interface of multiple interactions, playing an integral part in maintaining ho-meostasis in the heart.3,4 Under physiological conditions, cardiac fibroblasts contribute to the structural, mechanical