Effects of expanded resident cardiac macrophage numbers on disease pathology

Here we employed a novel gain of function approach specific to the heart to selectively enhance either CX3CR1+ or CCR2+ macrophages.

A robust increase in basal CCR2+ macrophages in the heart by targeted CCL2 expression did not induce inflammation, cause fibroblast activation, or impair cardiac function. However, sustained recruitment of CCR2+ macrophages reciprocally diminished numbers of self-renewing tissue resident macrophages at steady state, worsening cardiac fibrosis due to pressure overload induced by transverse aortic constriction. Conversely, augmented expression of colony-stimulating factor-1 in the heart promoted selective expansion of CX3CR1+ macrophages, which exerted no pathophysiological consequences at steady-state.