Circulating exosomal miR-92b-5p is a promising diagnostic biomarker of heart failure with reduced ejection fraction patients hospitalized for acute heart failure - PubMed (original) (raw)

Circulating exosomal miR-92b-5p is a promising diagnostic biomarker of heart failure with reduced ejection fraction patients hospitalized for acute heart failure

Tao Wu et al. J Thorac Dis. 2018 Nov.

Abstract

Background: Circulating microRNA (miRNA) biomarkers have been extensively reported in cardiovascular diseases (CVDs). However, serum exosomal miRNA (exo-miRNA) as biomarker in patients with heart failure (HF) with reduced ejection fraction (HFrEF) remain largely unexplored. We sought to investigate the potential of three types of serum exo-miRNAs as biomarkers for diagnosis in HFrEF patients who were admitted in hospital because of acute heart failure (AHF).

Methods: A total of 28 HFrEF patients hospitalized for AHF, including de novo AHF and acute decompensated HF, and 30 volunteers as control group (CG) from 2015 to 2017 were enrolled in this study. Serum exo-miRNAs were extracted and analyzed by NaNOZS-90, electron microscopy, and western blotting. Three types of serum exo-miRNAs (exo-miR-92b-5p, -192-5p, and -320a) were assessed by quantitative real time polymerase chain reaction (qRT-PCR).

Results: The particle size was confirmed as 40-150 nm using NaNOZS-90 and transmission electron microscopy. Exosomal biomarkers CD63 and Hsp70 were readily detected. The expression level of serum exo-miRNAs were transformed into log2-delta CT in the qPCR assay. The data showed that exo-miR-92b-5p was elevated in HFrEF patients compared with controls. Moreover, exo-miR-92b-5p was inversely correlated with the left ventricular fraction shortening (LVFS) and left ventricular ejection fraction (LVEF), whereas it was positively correlated with left atrial diameter (LAD), left ventricular diastolic diameters (LVDD) and systolic diameters (LVSD). A receiver operating characteristic (ROC) curve was generated for discrimination between HFrEF patients and controls based on exo-miR-92b-5p (P<0.001, sensitivity =71.4%, specificity =83.3%).

Conclusions: Exo-miR-92b-5p levels in the serum may serve as a marker for HFrEF diagnosis.

Keywords: Acute heart failure (AHF); circulating; diagnostic biomarker; exosome; heart failure with reduced ejection fraction (HFrEF); miR-92b-5p.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1

Figure 1

Characterization of serum exosomes. (A) The particle sizes of extracted exosomes were evaluated using NaNOZS-90; (B) serum exosomes were analyzed using microscopy and highlighted using black arrows. Scale bar =100 nm; (C) the biomarkers of exosomes (Hsp70 and CD63) were confirmed using Western blotting assay. E, exosomes; EDS, exosome-depleted supernatant.

Figure 2

Figure 2

Comparison the log2−delta CT of exo-miRNAs between HFrEF and CG. (A) exo-miR-92b-5p (Mann-Whitney U test; HFrEF vs. CG, P<0.001); (B) exo-miR-192-5p (Mann-Whitney U test; HFrEF vs. CG, P=0.050); (C) exo-miR-320a (Mann-Whitney U test; HFrEF vs. CG, P=0.087). HFrEF, heart failure with reduced ejection fraction; CG, control group.

Figure 3

Figure 3

Relationship analysis between log2−delta CT of exo-miR-92b-5p and echocardiographic indices. (A) log2−delta CT of exo-miR-92b-5p vs. LAD (Spearman correlation: r=0.480, P<0.001); (B) log2−delta CT of exo-miR-92b-5p vs. LVEF (Spearman correlation: r=–0.457, P<0.001); (C) log2−delta CT of exo-miR-192-5p vs. LVDD (Spearman correlation: r=0.434, P=0.001); (D) log2−delta CT of exo-miR-192-5p vs. LVFS (Spearman correlation: r=–0.502, P<0.001); (E) log2−delta CT of exo-miR-192-5p vs. LVSD (Spearman correlation: r=0.429, P=0.001). LAD, left atrial diameter; LVDD, left ventricular diastolic diameter; LVSD, left ventricular systolic diameter; LVEF, left ventricular ejection fraction; LVFS, left ventricular fraction shortening.

Figure 4

Figure 4

ROC curve for discriminating HFrEF from CG using log2−delta CT of exo-miR-92b-5p (AUC of 0.844, cutoff value =−6.09, sensitivity =71.4%, specificity =83.3%, P<0.001). ROC, receiver operating characteristic; HFrEF, heart failure with reduced ejection fraction; CG, control group; AUC, area under the curve.

Figure S1

Figure S1

Choice of internal reference. Six samples from healthy controls and patients with HFrEF were separately tested. H1 and H2 were from healthy controls. D1–D4 were from patients with HFrEF. HFrEF, heart failure with reduced ejection fraction.

References

    1. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013;128:e240-327. - PubMed
    1. Nichols M, Townsend N, Scarborough P, et al. Cardiovascular disease in Europe 2014: epidemiological update. Eur Heart J 2014;35:2929. 10.1093/eurheartj/ehu299 - DOI - PubMed
    1. Rohde LE, Bertoldi EG, Goldraich L, et al. Cost-effectiveness of heart failure therapies. Nat Rev Cardiol 2013;10:338-54. 10.1038/nrcardio.2013.60 - DOI - PubMed
    1. Metra M, Teerlink JR. Heart failure. Lancet 2017;390:1981-95. 10.1016/S0140-6736(17)31071-1 - DOI - PubMed
    1. Basuray A, French B, Ky B, et al. Heart failure with recovered ejection fraction: clinical description, biomarkers, and outcomes. Circulation 2014;129:2380-7. 10.1161/CIRCULATIONAHA.113.006855 - DOI - PMC - PubMed

LinkOut - more resources