Table 1.

Direct expression of cell cycle genes induces cardiomyocyte cell cycle entry.

Cell Cycle Gene	Studied Species	Highlights	References
Cyclin D1	Adult transgenic mice	Sustained DNA synthesis No evidence of complete cytokinesis	[26,28]
Cyclin D2	Adult transgenic mice	Observed DNA synthesis and reduced scar size after permanent coronary ligation in mice No evidence of complete cytokinesis	[13]
Cyclin G1	Mice hearts	Cyclin G1 expression stimulated DNA synthesis but arrested cytokinesis	[27]
Cyclin A2	Transgenic mice Rats, pigs	Modest cell proliferation in vitro but limited in vivo	[29,30,31,32]
CDK4–cyclin D1	Sprague–Dawley rats	Construction of a nuclear-localized cyclin D1 (D1NLS) to induce DNA synthesis	[33]
Cyclin B1–CDC2AF	Fetal, neonatal, and adult cardiomyocytes isolated from Wistar rat cardiomyocytes	Observation of increased cell numbers 72 h post-transfection by direct cell counting	[34]
CDK1, CDK4, cyclin B1, and cyclin D1	Post-mitotic mouse, rat, and human cardiomyocytes	Could induce stable cytokinesis in 15–20% of the adult cardiomyocytes expressing the four factors Self-limited through proteasome-mediated degradation of the protein products	[35,36]
P21 deacetylation by Sirt-1	Mice hearts	Sirt-1 deacetylated P21 and promoted its ubiquitination to release its inhibitory effect on the cell cycle	[37]
Cyclin-dependent kinase inhibitors (CKIs): P21, P27, and P57	SWISS CD1 mice Wistar rats	Knockdown of CKI using siRNA resulted in S phase induction. The subpopulation of cardiomyocytes progressed beyond karyokinesis	[23]
p38 MAP kinase inhibition	Rat cardiomyocytes	P38 knockout was associated with a 92.3% increase in neonatal cardiomyocyte mitosis and could promote cytokinesis in adult cardiomyocytes	[24]