MicroRNA as a Therapeutic Target in Cardiac Remodeling

Table 3

Summary of reported miRNAs and their targets in cardiac apoptosis.

miRNAs	Targets	Effector cells	Signal pathways	References
Antiapoptosis
miR-145	Bnip3	I/R mouse	FOXO	[72]
miR-199a	Hif-1α,; Sirt1	NRCMs; NRCMs	mTOR; AT1R	[89]
miR-21	PDCD4	NRCMs	NF-kB	[83]
miR-328	Atp2a2	H9C2 cells		[84]
miR-214	NCX1; PTEN	NRCM and miR-214 KO mouse; I/R mouse	Calcium signaling; PI3K-AKT	[87]; [92]
miR-24	Bim	NMCMs	Mitochondrial apoptosis	[85, 86]
miR-146b	RNase L	H9c2 cells	NF-kB	[91]
miR-378	Caspase-3	H9c2 cells and AMI rat	MAPK	[80]
miR-494	PTEN; ROCK1; CaMKIIδ; FGFR2; LIF	miR-494 TG Mouse; miR-494 TG Mouse; miR-494 TG Mouse; miR-494 TG Mouse; miR-494 TG Mouse	PI3K-AKT; cGMP-PKG; HIF1; PI3K-AKT; TNF	[73]
miR-499	Drp1	Male C57BL/6 mice	Mitochondrial pathway	[74]
miR-185	Nhe1	NRVMs	cAMP	[79]
miR-30 family	β1AR,; β2AR,; Giα2,; P53; Drp1	MI rat, DOX-induced HF rat, ARCM and H9c2 cells; MI rat, DOX-induced HF rat, ARCM and H9c2 cells; MI rat, DOX-induced HF rat, ARCM and H9c2 cells; NRCMs; NRCMs	β-adrenergic pathway; β-adrenergic pathway; β-adrenergic pathway; p53; mitochondrial pathway	[75, 76]
miR-210	Efna3,; Ptp1b; AIFM3	Mouse HL-1 cardiomyocytes and adult FVB mice; Mouse HL-1 cardiomyocytes, adult FVB mice; H9c2 cells,neonatal rat cardiomyocytes (NRCM)	VEGF signaling; VEGF signaling; Mitochondrial apoptosis	[81, 82]
miR-92a	NF-kB p65	rat H9c2 cells	NF-kB	[94]
miR-675	VDAC1	DCM	Mitochondrial apoptosis	[78]
miR-138	Lcn2	HL-1 cells	Mitochondrial apoptosis	[96, 97]
miR-124	STX2	Male BALB/c rats	miR-124a/STX2 pathway	[88]
Proapoptosis
miR-1	HSP60; Bcl-2; PKCε	LNA-antimiR-1 treated mouse; H9c2 cells and I/R rat; LNA-antimiR-1 treated mouse	RNA degradation; Mitochondrial apoptosis; cGMP-PKG	[75, 102]
miR-200c	GATA-4	NMCMs	cGMP-PKG	[93]
miR-363	Notch1	Rat H9C2 cell	Notch signaling	[90]
miR-122	caspase-8	NMCMs	ERK-MAPK	[99]
miR-181c	Bcl-2	NMCMs	Mitochondrial apoptosis	[77]
miR-15	Chek1	C57BL/6 mice and TG mouse		[104]
miR-34a	PNUTS; ALDH2	NRCMs and MI rat; NRCMs and MI rat	Oxidative stress; Oxidative stress	[106, 107]
miR-378	IGF1R	NMCMs and H9C2 cells	MAPK	[100]
miR-27a	IL-10	Sprague-Dawley rats and H9c2 cell	Interleukin 10 (IL-10) pathway	[95]
miR-29	PIO	H9c2 cells	PPAR	[98]
miR-28	PDK1; ALDH2	NMCMs; NMCMs	PDK1/Akt/mTOR-dependent signaling; AMPK and Akt-mTOR signaling.	[101, 105]
miR-195	Sirt1; Bcl-2	C57BL/6 mouse and NMCMs; C57BL/6 mouse and NMCMs	AMPK; Mitochondrial apoptosis	[103]

AIFM3: apoptosis inducing factor; ALDH2: aldehyde dehydrogenase 2; Bcl-2: B-cell CLL/lymphoma 2; Bim: Bcl2 like 11; Bnip3: Bcl2/adenovirus E1B 19 kDa interacting protein 3; β1AR: adrenoceptor β 1; β2AR: adrenoceptor β 2; CaMKIIδ: calcium/calmodulin-dependent protein kinase II, δ; Chek1: checkpoint kinase 1; CypD: Cyclophilin+D; Drp1: dynamin-related protein-1; Efna3: ephrin A3; FGFR1: fibroblast growth factor receptor 1; Giα2: G protein α i subunit; Hif-1α: hypoxia-inducible factor 1, α subunit; HSP60: heat shock protein 60; IGF-1R: insulin-like growth factor 1 receptor; IL-10: interleukin 10; Lcn2: lipocalin-2; LIF: leukemia inhibitory factor; NCX1: sodium/calcium exchanger 1; Nhe1: Na+/H+ exchanger 1; PDCD4: programmed cell death 4; PDK1: 3-phosphoinositide-dependent protein kinase-1; PKCε: protein kinase c beta1; PTEN: phosphatase and tensin homolog; Ptp1b: Protein Tyrosine Phosphatase-1B; P53: tumor protein p53; p65: tumor protein p65; ROCK1: Rho associated coiled-coil containing protein kinase 1; SIRT1: Sirtuin 1; SMAD7: SMAD family member 7; DCM: diabetic cardiomyopathy.