11 research outputs found
Synthesis of nonsymmetrically substituted 2,3-dialkoxyphenazine derivatives and preliminary examination of their cytotoxicity
Relations between circulating and myocardial fibrosis-linked microRNAs with left ventricular reverse remodeling in dilated cardiomyopathy
Right ventricular morphology and function is not related with microRNAs and fibrosis markers in dilated cardiomyopathy
Background: The relationship between right ventricle (RV), extracellular matrix (ECM) fibrosis and fibrosis-linked, circulating microRNAs in dilated cardiomyopathy (DCM) is unknown.
Aim: The aim of the study was to uncover the associations between serum markers of ECM metabolism and circulating microRNAs with RV morphological and functional parameters.
Methods: The study population consisted of 70 consecutive DCM patients (ejection fraction 24.4 ± ± 7.4%). Based on detailed echocardiographic assessment — 15 patients had normal RV, whereas 55 patients had RV dilatation (RVD) and/or RV systolic dysfunction (RVSD). Procollagens type I and III carboxy- and amino-terminal peptides, osteopontin (OPN), TGF1-b1, connective tissue growth factor (CTGF), MMP-2, MMP-9 and TIMP-1 were measured in serum as well as expression of miR-21, miR-26, miR-29, miR-30 and miR-133a. All patients underwent endomyocardial biopsy.
Results: Biopsy-proven fibrosis was evenly distributed in two groups. Serum levels of fibrosis markers did not differ between groups. OPN, CTGF, MMP-2, and TIMP-1 correlated with RV parameters. Only miR-133 a was differently expressed in both groups. MiR-21, miR-26, miR-30, and miR-133a correlated with RV morphological but without functional parameters. Not a single marker of fibrosis was independently associated with RV. MiR-30 was associated with RV impairment in the logistic regression model adjusted for age, sex, body mass index, and disease duration; however, lost its significance in the more comprehensive model.
Conclusions: Right ventricle structural and functional abnormalities are common in DCM. ECM fibrosis and serum markers are not associated with RV impairment. The prognostic value of studied microRNAs on RV is limited in DCM
The relationship between myocardial fibrosis and myocardial microRNAs in dilated cardiomyopathy : a link between mir-133a and cardiovascular events
It is unknown whether fibrosis‐associated microRNAs: miR‐21, miR‐26, miR‐29, miR‐30 and miR‐133a are linked to cardiovascular (CV) outcome. The study evaluated the levels of extracellular matrix (ECM) fibrosis and the prevalence of particular microRNAs in patients with dilated cardiomyopathy (DCM) to investigate any correlation with CV events. Methods: Seventy DCM patients (48 ± 12 years, EF 24.4 ± 7.4%) underwent right ventricular biopsy. The control group was comprised of 7 patients with CAD who underwent CABG and intraoperative biopsy. MicroRNAs were measured in blood and myocardial tissue via qPCR. The end‐point was a combination of CV death and urgent HF hospitalization at the end of 12 months. There were differential levels of circulating and myocardial miR‐26 and miR‐29 as well as myocardial miR‐133a when the DCM and CABG groups were compared. Corresponding circulating and myocardial microRNAs did not correlate with one another. There was no correlation between microRNA and ECM fibrosis. By the end of the 12‐month period of the study, CV death had occurred in 6 patients, and a further 19 patients required urgent HF hospitalization. None of the circulating microRNAs was a predictor of the combined end‐point; however, myocardial miR‐133a was an independent predictor in unadjusted models (HR 1.53; 95% CI 1.14‐2.05; P < .004) and adjusted models (HR 1.57; 95% CI 1.14‐2.17; P < .005). The best cut‐off value for the miR‐133a level for the prediction of the combined end‐point was 0.74 ΔCq, with an AUC of 0.67. The absence of a correlation between the corresponding circulating and myocardial microRNAs calls into question their cellular source. This study sheds new light on the role of microRNAs in ECM fibrosis in DCM, which warrants further exploration