Deregulated hepatic microRNAs underlie the association between non-alcoholic fatty liver disease and coronary artery disease.

Abstract

Non-alcoholic fatty liver disease (NAFLD) appears to be a new risk factor for the development of coronary artery disease (CAD). Members of a class of non-coding RNAs, termed microRNAs (miRNAs), have been identified as post-transcriptional regulators of cholesterol homoeostasis and can contribute to the development of NAFLD. The aims of this study were to (i) to assess the relationship between NAFLD and sudden cardiac death (SCD) from severe CAD in forensic autopsies and (ii) to quantify several hepatic miRNAs previously associated with lipid metabolism and NAFLD to correlate their expression with the presence of NAFLD, CAD, obesity parameters and postmortem lipid profile. A total of 133 cases of autopsies with SCD and established CAD (patient group, CAD-SCD) and 106 cases of non-CAD sudden death (control group, non-CAD-SD) were included. miRNAs were quantified in frozen liver tissues. Males predominated in both groups. Patients more frequently exhibited NAFLD and necroinflammatory steatohepatitis (NASH) than controls (62% vs 26%, P = 0.001 and 42% vs 26%, P = 0.001 respectively). In both groups, the presence of NAFLD correlated with body mass index and abdominal circumference (P < 0.05). An increase in miR-34a-5p and a decrease in miR-122-5p and -29c-3p in patients with NASH vs controls without NAFLD were observed (P < 0.05). Finally, significant correlations between miR-122-5p and unfavourable lipid profile and also hs-CRP and miR-34a-5p were noted. CAD is associated with NAFLD and NASH. The hepatic miRNAs studied appear to be associated with NAFLD severity and may promote CAD through lipid metabolism alteration and/or promotion of the systemic inflammation.