Abstract 13280: Plasma Extracellular microRNAs Associated With Cardiovascular Disease Risk Factors in Middle-Aged and Older Populations

Abstract

Background: Extracellular microRNAs (miRNAs) are a class of non-coding RNAs that resist degradation and remain stable in the extracellular milieu where they contribute to various physiological and pathological processes by facilitating intercellular signaling. Previous studies have reported associations between miRNAs and cardiovascular diseases (CVD); however, the plasma miRNA signatures of CVD and its risk factors have not been fully elucidated at the population level. Methods: Plasma miRNA levels were measured in 4,440 Framingham Heart Study (FHS) participants from the Third Generation and Omni II cohorts using qRT-PCR. Linear regression analyses were conducted to test the cross-sectional associations of each miRNA with CVD risk factors, including systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides, HDL and total cholesterol, blood glucose, BMI, and cigarette smoking. Prospective analyses of the associations of miRNAs with new-onset obesity, hypertension, type 2 diabetes, CVD, and all-cause mortality were conducted using proportional hazards regression. A false discovery rate threshold of 0.05 was applied for each risk factor and outcome individually. Replication was carried out in 2,000 Rotterdam Study (RS) participants with data on plasma miRNA levels measured using RNA-seq. Pathway enrichment analyses were conducted and gene targets were predicted for miRNAs associated with five or more risk factors in FHS. Results and Conclusions: In FHS, six miRNAs (miR-193b-3p, miR-122-5p, miR-365a-3p, miR-194-5p, miR-192-5p, miR-193a-5p) were associated with five or more CVD risk factors. This miRNA signature was enriched for biological processes and cellular pathways associated with CVD; many of the genes annotated to these pathways are predicted targets of the identified miRNAs. In RS, miR-193b-3p, miR-194-5p, and miR-193a-5p were associated with two or more risk factors. Prospective analysis revealed eight miRNAs associated with all-cause mortality only in FHS, including miR-193b-3p, miR-122-5p, miR-192-5p, and miR-193a-5p. These findings suggest plasma miRNA levels are associated with CVD risk factors and could provide opportunities to investigate their possible contributions to CVD pathogenesis.