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Objective:The aim of this study was to explore the differences in microRNA (miRNA) profiles in peripheral blood mononuclear cells (PBMCs) between coronary heart disease (CHD) patients with and without heart failure (HF) and to assess the values of differentially expressed miRNAs (DEMs) regarding HF risk in CHD patients.Methods:Six CHD patients with HF and six age- and gender-matched CHD patients without HF were enrolled in the exploration stage, and 44 CHD patients with HF and 42 age- and gender-matched CHD patients without HF were recruited in the validation stage. Peripheral blood samples were collected from all the participants, and PBMCs were separated for miRNA detection. miRNA microarray and quantitative polymerase chain reaction were performed to assess the miRNA expression.Results:In the exploration stage, heat map analysis showed that CHD patients with HF could be distinguished from those without HF using PMBC miRNA expressions; 63 downregulated DEMs and 84 upregulated DEMs in PBMCs were identified in CHD patients with HF using volcano map, and top 8 DEMs were selected based on their p values. In the validation stage, PBMC miR-221, miR-19b-5p, and miR-25-5p were found to be markedly dysregulated in CHD patients with HF. Multiple logistic regression analysis showed PBMC miR-221, miR-19b-5p, miR-25-5p, and hypertension to be the independent predictive factors for HF in CHD patients. A receiver operating characteristic curve demonstrated that area under curve of the combination of miR-221, miR-19b-5p, miR-25-5p, and hypertension was 0.871 (95% CI: 0.794-0.944).Conclusion:CHD patients with and without HF could be differentiated according to PBMC miRNA profiles, and the combination of PBMC miR-19b-5p, miR-221, miR-25-5p, and hypertension correlates with an increased HF risk in CHD patients.

A previous study and a gene-annotation enrichment analysis for potential targets of the microRNA miR-202-3p both suggest that this microRNA might be implicated in cardiovascular and metabolic diseases. In the present study, the role of miR-202-3p in the pathogenesis of coronary heart disease (CHD) was explored. We conduct a case-control study to detect the expression levels of miR-202-3p in peripheral blood cells and found that miR-202-3p expression was significantly higher in CHD cases than in controls (P < 0.001). miR-202-3p levels were negatively correlated with platelet distribution width (r = −0.348, P = 0.002) and mean platelet volume (r = −0.29, P = 0.01). Further functional analyses suggested that stimulation with oxidized low-density lipoprotein (ox-LDL) induced miR-202-3p expression, and that this microRNA suppressed the formation of ox-LDL-induced macrophage foam cells derived from THP-1 cells in a feedback manner. In addition, miR-202-3p overexpression modulated the expression of several key genes involved in foam cell formation, including that of ABCG4, NCEH1I, and SCARB2. In summary, miR-202-3p was associated with CHD, exerting a protective role against CHD by feedback suppression of ox-LDL-induced macrophage foam cell formation.

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