Role of miRNA in the Regulatory Mechanisms of Estrogens in Cardiovascular Ageing

Table 3

Cardiovascular-related miRNAs associated with estrogens and ageing.

miRNA	Ageing	Estrogen	Tissue/cell	Function (target)	References
miR-126		+	Endothelial cells	Endothelial proliferation, migration, tube formation, and monocyte adhesion (Spred1 and VCAM1)	[127]
	+		Endothelial cells	Senescence-associated compensatory mechanism (Spred1)	[134]
		−	Lymphocytes	Unexplored	[128]
miR-106	−		Endothelial cells	Unexplored (p21/CDKN1A)	[136]
		−	VSMCs	Unexplored	[97]
		−	Cardiac fibroblasts	Regulation of cardiac fibrosis via ERβ (Rasa1 and Rasa2)	[135]
miR-221/222	+		Endothelial cells	Suppression of eNOS and p^Ser1177-eNOS	[142]
	+		Aorta	Unexplored	[173]
		f < m	Cardiomyocytes	Regulation of eNOS expression (Ets-1)	[143]
miR-143/145		+	PASMCs	SMC and EC cell migratory phenotypes	[150]
miR-30b-5p		+	Endothelial cells	Unexplored	[98]
miR-23a	+		Endothelial cells	Unexplored	[164]
	+		Fibroblasts	Telomere dysfunction (TRF2)	[165]
		−	Myocardium	Loss of cardiac gap junctions (CX43)	[166]
		−	Cardiomyocytes	Ventricular remodeling (PGC1)	[169]
miR-203	+		Aortic SMCs	VSMC stiffness (Src and ERK)	[173]
		+	Aortic SMCs	Inhibition of VSMC proliferation (Abl1 and p63)	[97]
miR-144	+		Endothelial cells	Antioxidant response (NRF2)	[176]
miR-146a	+		Endothelial cells	Proinflammatory status marker (IRAK1)	[180]
	−		Endothelial cells	Senescence-like phenotype (NOX4)	[181]
		−	Lymphocytes	Regulation of LPS-induced IFN-γ (unknown)	[128]
miR-21	+		Heart	Unexplored	[182]
	+		Endothelial cells	Decrease angiogenesis and cell proliferation (NFIB and CDC25A)	[164]
	−		Endothelial cells	Antiproliferative effect (associated with PTEN and p27)	[142]
		−	Cardiac fibroblasts	Regulation of cardiac fibrosis (SPRY1, Rasa1, and Rasa2)	[135]
miR-34	+		Aorta	Unexplored	[173]
	+		Aorta/VSMCs	Promotes VSMC senescence and inflammation (SIRT1)	[192]
	+		Endothelial cells	Cell growth arrest and senescence (SIRT1)	[191]
	+		Cardiomyocytes	Age-associated cell death (PNUTS/PPP1R10)	[190]
		−	Endothelial cells	Regulation of eNOS expression (SIRT1)	[194]
miR-22	+		Cardiac fibroblasts	Induction of cellular senescence and migratory activity (OGN)	[196]
	+		Cardiomyocytes	Inhibition of cardiac autophagy and cell hypertrophy (Akt3, Hdac6, and Ppara)	[197]
		−	Cardiomyocytes/myocardium	Increased antioxidant defense (SP1)	[198]
miR-125	+		Endothelial cells	Impaired angiogenesis (RTEF1)	[202]
		+	Macrophages	Inhibitor of NF-κB signaling (κB-Ras2)	[201]
		−	Lymphocytes	Unexplored	[128]

Positive or negative associations with ageing and estrogens are represented, and the tissue or cell type used, miRNA-related function, and described miRNA target are shown. Sex differences are indicated where appropriate (f: female; m: male). SMC: smooth muscle cell; VSMC: vascular SMC; PASMC: pulmonary artery SMC.