Plasma levels of lipometabolism-related miR-122 and miR-370 are increased in patients with hyperlipidemia and associated with coronary artery disease

Abstract

BackgroundHyperlipidemia plays a crucial role in the development and progression of coronary artery disease (CAD). Recent studies have identified that microRNAs (miRNAs) are important regulators of lipid metabolism, but little is known about the circulating levels of lipometabolism-related miRNAs and their relationship with the presence of CAD in patients with hyperlipidemia.MethodsIn the present study, we enrolled a total of 255 hyperlipidemia patients with or without CAD and 100 controls with normal blood lipids. The plasma levels of four known lipometabolism-related miRNAs, miR-122, miR-370, miR-33a, and miR-33b were quantified by real-time quantitative PCR. Blood levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol were determined. Furthermore, the severity of CAD was assessed with the Gensini score system based on the degree of luminal narrowing and its geographic importance.ResultsOur results revealed for the first time that plasma levels of miR-122 and miR-370 were significantly increased in hyperlipidemia patients compared with controls, and the levels of miR-122 and miR-370 were positively correlated with TC, TG, and LDL-C levels in both hyperlipidemia patients and controls. Multiple logistic regression analysis demonstrated that the increased levels of miR-122 and miR-370 were associated with CAD presence, even after adjustment for other cardiovascular risk factors. Furthermore, miR-122 and miR-370 levels were positively correlated with the severity of CAD quantified by the Gensini score. However, both miR-33a and miR-33b were undetectable in plasma.ConclusionsOur results suggest that increased plasma levels of miR-122 and miR-370 might be associated with the presence as well as the severity of CAD in hyperlipidemia patients.

Circulating miR-122-5p/miR-133b Ratio Is a Specific Early Prognostic Biomarker in Acute Myocardial Infarction

“…21 MiR-122-5p was found to be overexpressed in the liver of hyperlipidemic animals 22 and increased in the bloodstream of patients with hyperlipidemia, being positively correlated with total cholesterol, triglycerides and low-density lipoprotein cholesterol. 23 In a porcine model of cardiogenic shock, Andersson et al 24 described a significant increase in the circulating levels of miR-122-5p, the magnitude of which was superior to the cardiac-enriched miRNAs. Interestingly, this increase did not seem to be explained by liver ischemia and was attenuated by therapeutic hypothermia.…”

Blood-Based Biomarkers for Metabolic Syndrome

“…Interestingly both miR-122 and miR-370 correlated positively with levels of total cholesterol, triglyceride, and low-density lipoprotein (LDL)-cholesterol in the plasma of both patient and control cohorts. Of note, miR-122 and miR-370 were both found to be decreased with statin treatment [40], suggesting these miRNAs as both potential diagnostic biomarkers for hyperlipidaemia and predictive biomarkers for response to statins. Table 2, row K) and collected visceral and subcutaneous abdominal adipose tissue biopsies.…”

“…However, circulating levels of miR-370 and miR-122 have been reported for individuals with hyperlipidaemia, a risk factor for MetS [39]. Gao et al [40] reported that in a cohort of 255 hyperlipidaemia individuals presenting with or without CAD in comparison with 100 healthy controls ( Table 2, row J), plasma levels of four lipid metabolism-associated miRNAs (miR-122, miR-370, miR-33a, and miR-33b) were investigated. Here, miR-122 and miR-370 were both found to be significantly increased in the plasma of hyperlipidaemia individuals compared with that of healthy controls, while miR-33a and miR-33b were undetected.…”

MicroRNA and Its Role in Cardiovascular Disease

“…Particularly increased level of miR-423-5p was well correlated with heart failure in different studies [53] [57]. Similarly level of miR-122 and miR-370 were positively correlated with total cholesterol, Triglycerides and LDL cholesterol (LDL C) and coronary artery disease (CAD) progression [71].…”

“…Similarly anti miR-33 therapy has found to be atheroprotective by increasing circulating HDL in mice model [70]. A study done by Gao et al [71] in 355 Chinese patients with hyperlipidemia found that level of miR-122 and miR-370 were positively correlated with total cholesterol, Triglycerides and Low density lipoprotein cholesterol C (LDL-C) and coronary artery disease (CAD) progression.…”