Circulating microRNAs in predicting fibrosis in hypertrophic cardiomyopathy: A systematic review

Table 1 Overview of studies on circulating microRNAs in predicting fibrosis in hypertrophic cardiomyopathy

Ref.	Study design	Sample size	Population	Method of miRNA detection	Method of fibrosis assessment	Key findings
Human studies
Angelopoulos et al[23]	Case-control study	50	27 HCM patients, 13 hypertensive cardiomyopathy patients, 10 controls	miR-21 and -29 assessed by qRT-PCR	LGE by CMR	miR-21 upregulated in HCM and correlated with extensive myocardial fibrosis; miR-29 did not differ between groups
Zhang et al[25]	Case-control study	25	21 HCM patients, 4 controls	68 miRNAs detected by Agilent Human miRNA Microarray Kit	LGE by CMR	22 miRNAs increased and 46 miRNAs decreased in HCM patients; miR-3960 and miR-652-3p levels correlated with LV hypertrophy; miR-642a-3p levels correlated with LV fibrosis
Thottakara et al[16]	Case-control study	40	24 HCM patients, 11 controls	6 miRNAs quantified by Human v3 miRNA Expression Assay Kit Code set and validated by RT-PCR	LGE by CMR	Elevated miR-4454 levels correlated with fibrosis in HCM patients
Huang et al[24]	Case-control study	72	42 HOCM patients and 30 controls	11 miRNAs initially detected by qRT-PCR; 2 further studied	Echocardiography and LGE by CMR	miR-221 correlated with myocardial fibrosis and hypertrophy in HOCM
Zhou et al[27]	Case-control study	69	30 HCM with fibrosis and 39 HCM without fibrosis patients	miR-29a assessed by qRT-PCR	Symptomatic assessment	lncRNA-MIAT associated with fibrosis in HCM by regulating miR-29a
Fang et al[28]	Case-control study	55	55 HCM patients	16 miRNAs validated using Taqman PCR	LGE by CMR	14 miRNAs upregulated in HCM patients; combination of 8 miRNAs showed high diagnostic value for diffuse myocardial fibrosis in HCM
Roncarati et al[26]	Case-control study	82	41 HCM patients, 41 controls	21 miRNAs assessed by qRT-PCR	LGE by CMR	12 miRNAs upregulated in HCM; 3 correlated with hypertrophy; only miR-29a correlated with hypertrophy and fibrosis
Animal studies
Zalivina et al[22]	Animal study	-	Murine mouse model	miR-199a-3p assessed by qPCR	N/A	miR-199a-3p contributed to cardiac fibrosis in HCM mice

HCM: Hypertrophic cardiomyopathy; HOCM: Hypertrophic obstructive cardiomyopathy; miRNA: microRNA; qRT-PCR: Quantitative reverse transcription polymerase chain reaction; RT-PCR: Reverse transcription polymerase chain reaction; LGE: Late Gadolinium Enhancement; CMR: Cardiac magnetic resonance; LV: Left ventricle; lncRNA-MIAT: Long non-coding RNA-Myocardial Infarction-Associated Transcript; PCR: Polymerase chain reaction; qPCR: Quantitative polymerase chain reaction, N/A: Not available.

Table 2 Key findings of microRNAs linked to fibrosis in hypertrophic cardiomyopathy

miRNA	Role in fibrosis	Diagnostic/prognostic potential
miR-199a-3p	Promotes fibrosis by modulating profibrotic genes and regulating the PI3K/AKT pathway	Potential therapeutic target to reduce cardiac fibrosis
miR-21	Associated with extensive myocardial fibrosis evident from imaging studies	Biomarker for assessing fibrosis severity through non-invasive imaging
miR-4454	Correlates with ventricular fibrosis and septal wall thickness	Biomarker for detecting fibrosis extent and ventricular structural changes
miR-221	Involved in myocardial remodeling, hypertrophy, and fibrosis regulation	Biomarker for myocardial hypertrophy, fibrosis, and cardiac function
miR-642a-3p	Positively correlated with LV fibrosis	Biomarker for LV fibrosis detection
miR-29a	Specific for fibrosis in HCM; regulates pathological fibrosis mechanisms	Diagnostic biomarker for assessing myocardial remodeling: AUC = 0.810
miR-133a-3p	Plays a role in diffuse fibrosis in HCM	Diagnostic biomarker for myocardial fibrosis; better utility in combination with other miRNAs

HCM: Hypertrophic cardiomyopathy; LV: Left ventricle; miRNA: microRNA; AUC: Area under the curve.