Abstract 12834: Increased Plasma Serotonin and Circulating microRNA-1914 Reflect Oxidative Stress and Play Crucial Roles in Atherosclerosis

Abstract

Introduction: Serotonin, synthesized from enterochromaffin cells, modulates vascular tonus and thrombus formation, and mediates development of atherosclerotic plaque. Oxidative stress is involved in vascular inflammation and progression of atherosclerosis. Hypothesis: We hypothesized that plasma serotonin plays a crucial role in increasing oxidative stress and aimed to identify the circulating microRNA(s) associated with serotonin ratio for coronary artery disease (CAD). Methods: Blood was sampled from 120 outpatients with cardiovascular risk factors but without a history of previous cardiovascular events. Serotonin levels both in platelet poor plasma (PPP) and whole blood (WB) were measured with HPLC, and the ratio of serotonin in PPP to that in WB (PPP/WB) was used as an index of platelet activation. For assessment of oxidative stress, serum levels of derivative reactive oxygen metabolites (d-ROM) were measured. Total RNA was isolated from subjects who were scheduled for coronary angiography with suspicion of CAD and a microRNA array analysis was performed. The expression levels of microRNAs were scaled by global normalization. Results: Serotonin levels in both PPP and PPP/WB ratio were significantly correlated with the d-ROM levels. Among enrolled patients, 25 subjects were diagnosed as having CAD. The levels of the PPP/WB ratio of serotonin, d-ROM, and CRP were significantly higher in subjects with CAD than in those without CAD. Logistic regression analysis performed with endpoint of having CAD revealed that the PPP/WB ratio of serotonin was independently associated with CAD. In subjects with CAD, 5 increased microRNAs and 30 decreased microRNAs were identified among more than 2000 microRNAs as compared to those without CAD. Among candidate microRNAs, expression of microRNA-1914 showed significant inverse correlation with PPP/WB ratio (r=-0.61, P<0.05) and d-ROM levels (r=-0.63, P<0.05). Conclusions: A significant association among platelet activation assessed by PPP and PPP/WB ratio and oxidative stress assessed by d-ROM, was detected in individuals with cardiovascular risk factors. Targeting serotonin-oxidative stress axis, and circulating microRNA-1914 may serve as novel strategy for diagnosis of atherosclerotic CAD.