Cardiac fibroblasts in pressure overload hypertrophy: the enemy within?

Abstract

Cardiac fibroblasts have been long recognized as active participants in heart disease; however, their exact physiological and pathological roles remain elusive, mainly due to the lack of specific markers. In this issue of the JCI, Moore-Morris and colleagues used a fibroblast-specific collagen1a1-GFP reporter to demonstrate that fibroblast accumulation after aortic banding in murine hearts arises almost exclusively from proliferation of resident fibroblasts originating from both the epicardium and a previously unrecognized source, the endocardium. Further characterization of fibroblast origin and function in different types and stages of heart disease could lead to development of improved fibroblast-targeted cardiac therapies.

Figure 1. Cardiac fibroblasts in developing, adult, and pressure overloaded hearts.

(A) In the embryonic heart, most fibroblasts are derived from epicardium (pink). The fibroblast lineage described by Moore-Morris et al. is generated from the atrioventricular canal endocardium (green) and migrates down the IVS. (B) In the adult heart, the dominant fraction of fibroblasts (∼90%) in the RV and LV are of epicardial origin, while 64% of fibroblasts in the IVS derive from the endocardium. (C) In response to pressure overload, the heart becomes hypertrophic and undergoes fibrosis. In response to pressure overload, both epicardium-derived and endocardium-derived fibroblast lineages proliferate and accumulate in interstitial and perivascular regions along with collagen I (black). The LV undergoes more fibrosis than the RV. Endocardium-derived fibroblasts participate in perivascular fibrosis in the IVS but not in the LV or RV. These two resident lineages account for approximately 95% of fibroblasts in the healthy and pressure-overloaded ventricles.