Table 2.

Emerging key modulator axis induce stable myocardial cell cycle re-entry and cardiac renewal.

Modulator	Ki67+ CM (%)	Model of cardiac injury	Regenerative signal axis
CHK1111	Rise 6.5% in vitro Rise 2.8% in vivo	AR in neonatal mice LAD ligation in adult mice	Targets mTORC1, activates P70S6K, and re-opens the regeneration window
HOXB13112	Rise 2.4% in vivo	LAD ligation in neonatal mice LAD ligation in adult mice	Meis1-Hoxb13 double-knockout displays CM mitosis, sarcomere disassembly and improved cardiac function.
Gp130113	Rise 1.9% in vitro Rise 4.1% in vivo	AR in adult mice LAD ligation in adult mice	Promotes cardiomyocyte proliferation by activating YAP via Src kinase
LRP6114	Rise 4.2% in vitro Rise 1.7% in vivo	LAD ligation in neonatal mice LAD ligation in adult mice	Regulates cardiomyocyte proliferation through the ING5/P21 pathway
PKM2115	Rise 3.4% in vivo	LAD ligation in adult mice	Interacts with β-catenin and activates both G6pd and the pentose phosphate pathway to provide nucleotides for DNA synthesis post-MI
ERBB218	Rise 2.7% in vitro Rise 0.45% in vivo	LAD ligation in adult mice	ERBB2-ERK-YAP mechanotransduction involving EMT-like features was found to cause strong cardiac regeneration.
PITX238	Unknown	AR in adult mice LAD ligation in adult mice	Pitx2-YAP interaction is found to be important for myocardial proliferation and regeneration.
MYDGF45	Rise 0.19% in vitro Rise 0.006% in vivo	AR in neonatal mice LAD ligation in adult mice	Activates c-MYC/FoxM1 pathway and goes against heart failure after cardiac injury
HIF1α32	Rise 0.003% in vivo	Chronic hypoxia exposure	Hypoxia exposure leads to cell cycle re-entry and cardiomyocyte expansion and induces myocardial regeneration in mammals.