Table 1 Pathophysiological role of cardiovascular miRs in heart diseases

1.

miR-1

Cardiac and skeletal muscle

SRF (specifically in heart); MEF2 and MyoD (specifically in skeletal muscles)

Cardiac & skeletal muscle proliferation & differentiation; pro-apoptotic in infarcted heart; arrhythmogenesis; inhibition of cardiac hypertrophy

Cardiac hypertrophy, apoptosis, heart failure, arrhythmia

Reported in diabetic cardiomyopathy; may also regulate diabetes-associated arrhythmia and cardiac regeneration.

Downregulation of Pim-1, calmodulin and MEF2a; Hand2, RasGAP, Cdk9, Rheb, fibronectin, HSP60 and HSP70; HDAC4, IGF-1; Cx43 protein; Kir2.1; Junctin, KCNJ2, GJA1, Irx5

TAC, transgenic mice with AKt overexpression and exercise-induced hypertrophy model in rats; neonatal rat ventricular cardiomyocytes, hypertrophic human atria and ventricles, STZ-diabetic mice, HG-exposed rat cardiomyocytes

[11–25]

2.

miR-133

Cardiac and skeletal muscle

SRF; MEF2; MyoD;

Promotes cardiogenesis; cardiac regeneration by promoting proliferation; prevents differentiation; decreases heart rate; inhibition of cardiac hypertrophy; inhibition of fibrosis in left ventricle

Cardiac hypertrophy, heart failure, arrhythmia

Reported in diabetic cardiac hypertrophy; diabetes-associated arrhythmia. May be implicated in cardiac regeneration in diabetic heart.

Downregulation of RhoA; Cdc42; Nelf-A/WHSC2; PP2A, ERG, caspase 9, SRF, KCNQ1, nPTB; CyclinD; Sp-1; CTGF

TAC, transgenic mice with AKt overexpression and exercise-induced hypertrophy model in rats; neonatal rat ventricular cardiomyocytes, hypertrophic human atria and ventricles; STZ-type I diabetic mice model; HG-exposed rat cardiomyocytes

[13, 16, 20, 26–29]

3.

miR-126

Endothelial cells

ETS1 and ETS2

Promotes angiogenesis, anti-apoptotic

Atherosclerosis, CAD, heart failure, Myocardial infarction

May be involved in Diabetes-mediated atherosclerosis and post-MI remodeling

Upregulation of angiopoietin receptor Tie-1, c-kit, interleukin-8; CXCL12. VEGF, VEGF receptors via repression of Spred-1, Downregulation of EGFL7

k/o mice; Apoe^−/− mice model of atherosclerosis

[30–40]

4.

miR-208a

Cardiac muscle

αMHC

Regulation of cardiac conduction system by controlling atrial depolarization; regulates gene network in stem cell differentiation of cardiomyocytes, upregulation of βMHC

Cardiac hypertrophy, cardiac remodeling, arrhythmia; human dilated cardiomyopathy; fibrosis

May be implicated in diabetic cardiomyocyte hypertrophy, arrhythmia and in cardiac regeneration.

Downregulation of THRAP1, myostatin, βMHC

miR-208a mutant mice, k/o mice, transgenic mice with miR-208a overexpression, TAB-induced hypertrophy in mice

[41–44]

5.

miR-499

Cardiac ventricles

MRFs and Eos

Cardiac regeneration by regulation of cardiac differentiation and proliferation; cardiac gene reprogramming; anti- apoptotic; regulates stress response genes

myocardial infarction; cardiac hypertrophy; fibrosis and cardiac conduction

Diabetic cardiomyopathy. May be implicated in cardiac regeneration in diabetic heart.

Repression of histone deacetylase 4 and Sox6 proteins; Downregulation of KCNN3 gene encoding SK3 channels; Gadd45alpha; calcineurin; cyclin D1; Bmp2k, Cpne3, Hipk1, Hipk2, Map3k2 (Mekk2), Stk35, Taok1, and Uhmk1

Transgenic mice with miR-499 overexpression, TAB-induced hypertrophy, human heart, HL-1 cells transfected with miR-499 mimic, neonatal rat cardiomyocytes exposed to anoxia

[45–52]

6.

miR-132

endothelial cells, Neuron cells

CREB, VEGF

Promotes angiogenesis, regulates cardiac hypertrophy and autophagy, modulates inflammation

myocardial infarction; cardiac hypertrophy; Heart Failure; atherosclerosis and CAD

May be implicated in post-MI, heart failure and cardiac regeneration in diabetic heart.

Downregulation of p120RasGap

HUVECs, Human embryonic stem cell vasculogenesis model

[53–56]