Circulating miR-185 might be a novel biomarker for clinical outcome in patients with dilated cardiomyopathy - PubMed (original) (raw)
Circulating miR-185 might be a novel biomarker for clinical outcome in patients with dilated cardiomyopathy
Miao Yu et al. Sci Rep. 2016.
Abstract
B cells contribute to the development of dilated cardiomyopathy (DCM) by inducing myocyte injuries and myocardial fibrosis. Our recent research indicated that microRNA (miR) -185 participated in human B-cell activation. Thus, this study was aimed to explore the relationship between miR-185 and DCM progression. Forty-one healthy volunteers and fifty newly diagnosed DCM patients were enrolled. The levels of plasma miR-185, TNF-α secreting B cells, and anti-heart autoantibody were detected. We found that the mean levels of plasma miR-185 in DCM patients were significantly higher than those in healthy controls. Furthermore, these DCM patients could be divided into miR-185(high) and miR-185(low) groups according to the cluster distribution. During one-year follow-up period, the miR-185(high) group showed apparent improvements in left ventricular ejection fraction, left ventricular end diastolic diameter, and NT-proBNP, accompanied by significant declines in both cardiovascular mortality and total admissions for heart failure re-hospitalizations. In addition, the levels of anti-β1-AR antibody and TNF-α secreting B cells were also reduced in miR-185(high) group. These findings suggested that high miR-185 levels might be associated with a favorable prognosis by repressing B cell function in DCM. The findings of this study need to be confirmed with larger sample size and longer duration of observation.
Figures
Figure 1. MicroRNA-185 Expression in Peripheral Blood of DCM Patients.
(A) MicroRNA-185 expressions were investigated in peripheral blood of healthy controls and DCM patients by TaqMan® microRNA assays at the time of enrollment (P = 0.037). (B) According to the levels of miR-185, DCM patients were divided into miR-185high group and miR-185low group (P < 0.001). The results are the mean ± SEM.
Figure 2. The Correlation of MiR-185 Levels and the Indexes of Cardiac Function in DCM Patients.
(A–C) The correlation analysis of miR-185 levels and LVEDD, LVEF and NT-proBNP at month 0 in DCM patients, the correlation index (R) is respectively −0.056, −0.038 and 0.021, all P > 0.05. (D–F) The correlation analysis of miR-185 levels and the reduction rates of LVEDD (R = 0.081), LVEF (R = −0.011) and NT-proBNP (R = 0.218) at 3rd month compared with the baselines at month 0 in DCM patients, all P > 0.05. (G–I) The correlation analysis of miR-185 levels and the reduction rates of LVEDD (R = 0.060), LVEF (R = 0.047) and NT-proBNP (R = 0.266) at 6th month compared with the baselines at month 0 in DCM patients, all P > 0.05. (J–L) The correlation analysis of miR-185 levels and the reduction rates of LVEDD (R = 0.446, P = 0.002), LVEF (R = 0.128, P > 0.05) and NT-proBNP (R = 0.390, P = 0.007) at 12th month compared with the baselines at month 0 in DCM patients. ΔLVEDD = (the baseline LVEDD at month 0- LVEDD in the follow-up period)/the baseline LVEDD at month 0, ΔLVEF = (LVEF in the follow-up period-the baseline LVEF at month 0)/the baseline LVEF at month 0, and ΔNT-proBNP = (the baseline NT-proBNP at month 0- NT-proBNP in the follow-up period)/the baseline NT-proBNP at month 0.
Figure 3. Kaplan-Meier Survival Curves for MiR-185high and MiR-185low Patients.
Figure 4. A Follow-up Study of Cardiac Function in MiR-185high and MiR-185low Patients.
(A) The reduction of LVEDD compared to that at the time of enrollment in miR-185high and miR-185low groups at 3rd (P > 0.05), 6th (P = 0.043) and 12th (P = 0.003) months. (B) The elevation of LVEF compared to that at the time of enrollment in miR-185high and miR-185low groups at 3rd (P > 0.05), 6th (P = 0.037) and 12th (P = 0.035) months. (C) The reduction of NT-proBNP compared to that at the time of enrollment in miR-185high and miR-185low groups at 3rd (P > 0.05), 6th (P = 0.011) and 12th (P = 0.022) months. (D–G) NYHA classification of the patients evaluated respectively at 0 (P > 0.05), 3rd (P > 0.05), 6th (P = 0.034) and 12th (P = 0.034) months. ΔLVEDD = (LVEDD in the follow-up period-the baseline LVEDD at month 0)/the baseline LVEDD at month 0, ΔLVEF = (LVEF in the follow-up period-the baseline LVEF at month 0)/the baseline LVEF at month 0, and ΔNT-proBNP = (NT-proBNP in the follow-up period-the baseline NT-proBNP at month 0)/the baseline NT-proBNP at month 0. Values are means ± SEM.
Figure 5. The Relationship between MiR-185 and B cell Function in DCM Patients.
(A) The levels of miR-185 in plasma were not changed during the follow-up period (P > 0.05). (B) The levels of miR-185 in B cells were not changed during the follow-up period (P > 0.05). (C) The levels of plasma TNF-α in miR-185high and miR-185low groups respectively at 0 (P = 0.024), 3rd (P = 0.019), 6th (P = 0.021) and 12th (P = 0.020) months. (D) The results of statistical analysis for the frequencies of TNF-α secreting B cells in miR-185high and miR-185low groups respectively at 0 (P = 0.014), 3rd (P = 0.016), 6th (P = 0.015) and 12th (P = 0.007) months. (E) Representative pictures from DCM patients for the frequencies of B cells expressing TNF-α. (F) The levels of plasma anti-ANT antibody detected by ELISA respectively at 0, 3rd, 6th and 12th months, all P > 0.05. (G) The levels of plasma anti-β1-AR antibody detected by ELISA respectively at 0 (P = 0.022), 3rd (P = 0.002), 6th (P = 0.034) and 12th (P = 0.035) months. (H) The levels of plasma MHC antibody detected by ELISA respectively at 0, 3rd, 6th and 12th months, all P > 0.05. (I) The levels of plasma anti-calcium channel antibody detected by ELISA respectively at 0, 3rd, 6th and 12th months, all P > 0.05. Values are means ± SEM.
References
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- Yu M. et al. TNF-alpha-secreting B cells contribute to myocardial fibrosis in dilated cardiomyopathy. J Clin Immunol 33, 1002 (2013). - PubMed
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