Cardiac-peripheral transvenous gradients of microRNA expression in systolic heart failure patients

Abstract

Aims: The aims of the study are to assess the levels of coronary sinus (CS) miRNAs of systolic heart failure (HF) patients in samples obtained during cardiac resynchronization therapy (CRT) device implantation and compare them to the peripheral systemic venous miRNA expression.

Methods and results: The cardiac specific miRNA levels were assessed in 60 patients, 39 HF patients with reduced ejection fraction and 21 control patients. The levels of four cardiac specified miRNAs (miR-21-5p, miR-92b-3p, miR-125b-5p, and miR-133a-3p) were compared between the peripheral samples of HF and controls and between peripheral venous in CS in the HF groups. Compared with controls, HF patients had higher peripheral serum venous levels of miR-125b-5p and miR-133-3p. In the HF group, the levels of expression were higher for miR-125b-5p and lower for miR-92, and miR-21-5p in the CS, compared with the peripheral venous circulation.

Conclusions: The differences in miRNA expressions in CS compared with those in the periphery suggest that changes that may occur at the levels of the myocardial tissue in HF may be more relevant to our understanding of the biological linkage between miRNA expression and HF, than the traditional analysis of systemic serum miRNA expression.

Keywords: Cardiac resynchronization therapy; Coronary Sinus; Systolic heart failure (HF); miRNA.

Figure 1

miR‐125b‐5p relative expression levels in (A) serum samples of HF(peripheral and CS samples) and control patients (peripheral samples), and (B)paired sample analysis of peripheral and CS serum samples of HF patients. Error bars indicate 95% Confidence Interval for the median. HF, heart failure; P, peripheral serum; CS, Coronary Sinus serum.

Figure 2

miR‐92b‐3p relative expression levels in (A) serum samples of HF (peripheral and CS samples) and control patients (peripheral samples),and (B) paired sample analysis of peripheral and CS serum samples of HF patients. Error bars indicate 95% Confidence Interval for the median. HF, heart failure; P, peripheral serum; CS, coronary sinus serum; n.s., not significant.

Figure 3

miR‐21‐5p relative expression levels in (A) serum samples of HF(peripheral and CS samples) and control patients (peripheral samples), and (B)paired samples analysis of peripheral and CS serum sample of HF patients. Error bars indicate 95% Confidence Interval for the median. HF, heart failure; P, peripheral serum; CS, Coronary Sinus serum; n.s., not significant.

Figure 4

miR‐133a‐3p relative expression levels in serum samples of HF (peripheral and CS samples) and control patients (peripheral samples). Error bars indicate 95% Confidence Interval for the median. HF, heart failure; P, peripheral serum; CS, coronary sinus serum; n.s., not significant.

Figure A1

Expression levels of miR‐16‐5p (A), miR‐1260a‐5p (B) and sum of miR‐16‐5p+miR‐1260a‐5p (C) are presented as cycle threshold (Ct) values for control peripheral, HF peripheral and HF CS samples. Kruskal–Wallis test was performed to evaluate differences between three groups of samples.