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Table 1 Cellular responses upon cardiac injury

From: Molecular regulation of myocardial proliferation and regeneration

 

Zebrafish

Neonatal mammals

Adult mammals

Endothelial cells (ECs)

Raldh2 increased in endocardium and retinoic acid signaling from endocardium is required for CM proliferation (Kikuchi et al., 2011b). Revascularization occurs via angiogenesis (Marin-Juez et al. 2016).

Arterial ECs migrate to the infarcted region and form collateral arteries in mice (Das et al. 2019).

Preexisting endothelial cells form new coronary blood vessels after injury in mice (He et al. 2017). Endocardial contribution to coronary arteries or vascular ECs after injuries is very limited (Tang et al. 2018).

CMs

Most of the adult CMs are mononuclear diploid cells and retain robust proliferative capacities (Poss et al. 2002; Gonzalez-Rosa et al. 2018). Regenerated CMs derive from the proliferation of preexisting CMs (Jopling et al. 2010; Kikuchi et al. 2010)

Cardiomyocytes are mononuclear diploids. After injury, pre-existing CMs are the source of cardiac regeneration (Porrello et al., 2011a).

Most adult CMs are polyploid. The level of CM proliferation after injury is very low (Bergmann et al. 2009; Ali et al. 2014).

Fibroblasts

Fibroblasts synthesize ECM collagen post-injury and are inactivated during scar resolution. Both fibroblasts and the ECM are necessary to stimulate CM proliferation and regeneration (Sanchez-Iranzo et al., 2018b).

ECM deposit after injury but only minimal fibrotic tissue can be observed 21 days after injury (Porrello et al., 2011a).

Fibroblasts proliferate, and deposit ECM after myocardial infarction.

Epicardium

Epicardium is activated after injury and restricted to injury area 7 days after injury. Epicardial derived cells differentiate into perivascular cells and myofibroblasts, but not CMs, or coronary endothelium (Kikuchi et al., 2011a; Gonzalez-Rosa et al. 2012).

Epicardium is activated after injury with increased expression of Wt1 and Raldh2. Tbx18+ epicardial cells give rise to minimal numbers of CMs in the neonatal mouse heart after injury (Cai et al. 2019)

Epicardium-derived cells do not produce cardiomyocytes, but secrete paracrine factors to regulate heart regeneration (Zhou et al. 2011)

Macrophages

Depletion of macrophages leads to impaired heart regeneration (Lai et al. 2017).

Embryonic-derived resident cardiac macrophages increase after injury and are essential for cardiac repair (Lavine et al. 2014).

Monocyte-derived macrophages were recruited after injury. Inhibition of Monocyte recruitment improves cardiac repair (Lavine et al. 2014).