MiR-222 in Cardiovascular Diseases: Physiology and Pathology

Table 1

Summary of physiological and pathological functions of miR-222 in heart.

	Cardiac; parameter	Model		Effects of miR-222	References
		In vitro	In vivo
Physiological function	Cardiomyocytes proliferation	Neonatal rat ventricular cardiomyocytes; Adult mice cardiomyocytes; Adult mice noncardiomyocytes	C57BL/6J,; exercise, and cardiac ischemia reperfusion surgery	Cardiomyocytes growth, proliferation, and survival in vitro ↑; Necessary for exercise-induced cardiac growth	[13, 17]
	Cardiac stem/progenitor cells differentiation	Mouse ESCs; Human ESCs	—	Sarcomere alignment and calcium handling ↑; Resting membrane potential ↓; cardiomyocytes maturation markers ↑	[18]
Pathological function	Ischemia reperfusion injury	—	miR-222 overexpression mice,; cardiac ischemia reperfusion surgery	Protecting against cardiac dysfunction after I/R	[17]
	Heart failure	—	miR-222 overexpression mice, cardiac-specific	Inducing heart failure; Inhibiting autophagy	[19]
		—	Human	miR-222 ↓ in HF patients with left ventricular assist devices	[20]
		Human aortic endothelia cells	—	LDL from HF patients ↓ miR-222	[21]
	Inflammation	HUVECs	—	HIV Tat protein ↓ miR-222; Involved in inflammatory pathway	[22]
		Adult mouse cardiomyocytes, nRCMs, MCECs, and nRCFs	C57BL/6J, C3H, viral myocarditis	Cardiac viral infection ↑ IFN through miR-222 emerging efficient viral clearance	[23]
	Atherosclerosis	—	Human	miR-222 ↓ in atherosclerotic plaque shoulder related to plaque rupture	[24]
	Tetralogy of Fallot	Primary embryonic mouse cardiomyocytes; P19 Cell Line	Human	↑ In heart tissue of patients ↑ migration, proliferation in embryonic mouse cardiomyocytes; ↓ Cardiomyogenic differentiation of P19 cells	[25]
	Ventricular septal defect	—	Human	Low level in patients with ventricular septal defect	[20]
	Peripheral artery disease	—	C57BL/6J,; Hindlimb ischemia surgery	↑ Skeletal muscle regeneration after hindlimb ischemia	[26]
	Artery damage	—	ApoE Knockout mice,; wire-induced artery injury	↑ During neointima formation	[27]