Prediction of coronary disease incidence in the general population by circulating RNY(YRNA)-derived small RNA
ABSTRACTDuring the development of atherosclerotic lesion, s-RNYs (small RNAs of about 24/34 nucleotides) are derived by the processing of long Ro-associated non-coding RNAs (RNYs) in macrophages. The levels of serum s-RNYs have been found significantly upregulated in patients with coronary heart disease (CHD) compared to age-matched healthy individuals. The present study aimed to examine the predictive value of serum s-RNYs for CHD events in the general population.Within the frame of nested-case-control study, the GENES study, we measured the absolute expression of a RNY-derived small RNA, the s-RNY1-5p, in the serum of healthy individuals who encountered a CHD event within 12 years of follow-up (n = 31) (Cases) and compared them to individuals who remained event-free (Controls) (n = 30).The expression of s-RNY1-5p in serum was significantly upregulated in Cases compared to Controls (p = 0.027). The proportion of CHD event-free was significantly higher among individuals with serum s-RNY1-5p below the median value (631 molecule / mL). In a multivariate model adjusted for age, smoking and treatment for hypertension, diabetes and dyslipidemia, the risk of CHD events increased more than 4-fold in individuals with serum s-RNY1-5p above the median value (HR, 4.36; 95%CI, 1.22-15.60). Significant association with CHD events was also observed when considering s-RNY1-5p as a continuous variable (p = 0.022). Serum s-RNY1-5p is an independent predictor of CHD in healthy individuals and could be considered as a biomarker in primary prevention of cardiovascular diseases.TRANSLATIONAL PERSPECTIVESHere, we reported that s-RNY1-5p was significantly upregulated in the serum of individuals who underwent CHD and was positively associated with CHD events. Those results argue in favor of s-RNY1-5p being a novel predictive molecular biomarker for cardiovascular events. In the future, measurement of s-RNY1-5p expression levels and other 5’ s-RNYs, such as s-RNY4-5p, could be used in clinical practice in addition to classical risk factors to identify those high-risk individuals who might benefit from prevention medicine.