Fanning the flames to regenerate the heart

Abstract

Damage to the adult mammalian heart is irreversible, and lost cells are not replaced through regeneration. In neonatal mice, prior to P7, heart tissue can be regenerated after injury; however, the factors that facilitate cardiac regeneration in the neonatal heart are not known. In this issue of the JCI, Aurora and colleagues evaluated the immune response following myocardial infarction in P1 mice compared with that in P14 mice, which have lost their regenerative capacity, and identified a population of macrophages as mediators of cardiac repair. Further understanding of the immune modulators that promote the regenerative properties of this macrophage subset could potentially be exploited to recapitulate regenerative function in the adult heart.

Figure 1. Macrophage depletion prevents regeneration of the neonatal mouse heart.

(A) Neonatal mouse pups are intravenously injected with clodronate-loaded liposomes (yellow), which are phagocytosed by macrophages (red). Clodronate uptake results in macrophage apoptosis and subsequent depletion (blue). Loss of macrophages in neonatal mice results in scarring and fibrosis following MI. (B) In untreated pups, macrophages infiltrate the injured heart and are distributed uniformly throughout the heart (red) following MI. Macrophage infiltration into the heart is proposed to stimulate coronary neovascularization, via paracrine secretion of proangiogenic factors, to support myocardial regeneration. LAD, left anterior descending artery.