MicroRNAs in the failing heart – Novel therapeutic targets?

Figures & data

Table I. miRNAs as therapeutic targets in animal models of HF.

Target	Model	Treatment	Outcome	Mechanism	References
miR-21	3 Weeks of TAC in mice	Antagomir-21 through jugular vein catheter for 3 days	Attenuation of interstitial fibrosis and cardiac hypertrophy	Derepression of SPRY1 in cardiac fibroblasts	Thum et al. (2008)
			Normalized fractional shortening
miR-208	Dahl rats on a high-salt diet	Tail vein injection of LNA-anti-miR every two weeks	Reduction in isovolumic relaxation time	Reversal of myosin switching	Montgomery et al. (2011)
			Reduction in cardiac hypertrophy
			Reduction in periartieriolar fibrosis
miR-652	4 Weeks of TAC in mice	Subcutaneous administration of LNA-anti-miR for 3 days	Improved fractional shortening/LVESD	Derepression of Jagged1 and Notch signaling	Bernardo et al. (2014)
			Reduced cardiomyocyte apoptosis
			Decreased cardiac fibrosis
miR-25	8 Weeks of TAC in mice	Tail vein injection of anti-miR daily for 3 days, followed by weekly injections for 3 weeks	Restoration of ESPVR and EF	Derepression of SERCA2a and improved Ca2 + uptake	Wahlquist et al. (2014)
			Increased survival
			Reduction in fibrosis
			Normalization of cardiomyocyte size

TAC: Transverse aortic constriction, LNA: Locked nucleic acid, LVSED: Left ventricular end-systolic dimension, ESPVR: End-systolic pressure–volume relationship, EF: Ejection fraction.

Table II. miRNAs as biomarkers for HF.

Study	miRNA(s)	Study population	Diagnostic accuracy (AUC from ROC analysis)
Tijsen et al. (2010)	miR-423-5p	HF cases, n = 30	HF vs healthy controls 0.91
		Non-HF dyspnea cases, n = 20	HF vs non-HF dyspnea 0.83
		Healthy controls, n = 39
Goren et al. (2012)	miR-423-5p	Chronic HF cases, n = 30	Combined miRNA-score, HF vs controls: 0.9
	miR-320a	Healthy controls, n = 30
	miR-22
	miR-92b
Corsten et al. (2010)	miR-499	Acute HF, n = 33	miR-499-5p 2-fold elevated in AHF, (p < 0.05)
		Healthy controls, n = 20	ROC N/A
Vogel et al. (2013)	miR-520d-5p	Non-ischemic HF cases, n = 53	Combined miRNA signature, HF vs controls: 0.81
	miR-558	Healthy controls, n = 39
	miR-122*
	miR-200b*
	miR-622
	miR-519e*
	miR-1231
	miR-1228*

HF: Heart failure, AUC: Area under the curve, ROC: Receiver-operating characteristic, N/A: not available.

Figure 1. Overview of miRNAs involved in the pathogenesis of heart failure. miRNAs and their respective target mRNAs in different cell types are shown.