Differential Expression of Peripheral Circulating MicroRNA-146a Between Patients with Atherosclerotic Vulnerable Plaque and Stable Plaque

Abstract

Atherosclerotic plaque rupture and subsequent cardiovascular complications threaten the population's health worldwide. The polymorphism of miR-146a rs2910164 was significantly associated with the risk of vulnerable plaques. However, it remains unclear whether the circulating miR-146a is differentially expressed in stable and vulnerable plaques and thus, serves as a potential biomarker.This study aims to analyze the differential expression of circulating miR-146a between patients with stable and vulnerable plaques to explore the potential molecular mechanisms.Public databases were searched from their inception up to November 2022. A study reporting the specific circulating miR-146a levels between patients with stable and vulnerable plaques was included. The study quality was assessed using the modified genetic 8-stars Newcastle-Ottawa scale. The differential expression levels of miR-146a were evaluated using the standardized mean difference (SMD).Eight studies with 978 patients were included and analyzed. The results showed that miR-146a expression levels were significantly higher in the vulnerable plaque population than in the stable plaque population (SMD: 1.91; 95% confidence interval: 1.35, 2.47; P < 0.01). A similar statistical significance was found in subgroup analyses regarding sample source, disease type, and vulnerable plaque characteristics. Sensitivity analysis suggested the robustness of the results. Analysis of downstream genes suggested that miR-146a-targeted regulation of ACTN4, SARM1, and ULK2 may affect intraplaque hemorrhage.Patients with vulnerable plaque have higher circulating miR-146a levels than those with stable plaque. However, based on the limitations of this study, high-quality studies are still needed to confirm the results.