92-OR: EMC10, a Novel Serum Predictor for Coronary Artery Disease, Exerts an Impact on the Development of Atherosclerosis via Negatively Modulating Endothelial Insulin Signaling

Cardiovascular disease is the leading cause of global mortality, accounting for about one third of deaths worldwide. Secreted proteins from metabolically regulated organs are released into circulation and exert impacts on the pathogenesis of cardiovascular disease. In this study, we identified a novel secreted protein, EMC10, that might influence the development of atherosclerosis. We initially observed that serum EMC10 is significantly decreased in patients with coronary artery diseases evidenced by coronary artery stenosis over 50 percent, compared with those suffering stenosis less than 50%. In addition, we found that the levels of serum Emc10 are even lower in patients who meanwhile suffered from hypertension. After adjusted for age, BMI, hypertension, and diabetes, the regression analysis revealed that serum EMC10 is an independent predictor for coronary artery diseases. To determine the role of EMC10 in cardiovascular disease, we established Emc10 whole body knockout mice and found that both the systolic and diastolic blood pressure are significantly decreased in EMC10 KO mice in comparison to wild type ones. Furthermore, in vitro experiments showed that EMC10 significantly decreases the insulin-stimulated phosphorylations of both Akt and eNOS, and conversely, significantly increases VCAM-1 mRNA in endothelial cells. Collectively, these preliminary data suggest EMC10 leads to endothelial insulin resistance and plays a role in the development of atherosclerosis, by which EMC10 is involved in the pathogenesis of cardiovascular disease. Our findings establish Emc10 as a novel modulator of endothelial insulin signaling and a potential target for the intervention of diabetic vascular diseases.