Abstract 12316: Metrnl Deficiency Destabilized the Atherosclerotic Plaque and Increased the Risk of Acute Coronary Syndrome

Abstract

Introduction: Metrnl has been recently identified as a myokine/adipokine that acts as an immune/metabolic regulator. Hypothesis: Metrnl might be exert an important role in acute coronary syndrome. Methods: Circulating Metrnl levels were evaluated in 983 subjects with acute coronary syndrome and healthy controls recruited from Jinan Central Hospital. Apolipoprotein E-deficient mice infected with Metrnl-silencing adenovirus were used for investigating the function of Metrnl in atherosclerotic plaques. The relevant molecular mechanisms were then explored in-vitro in siMetrnl transfected and Metrnl treated HUSMC cells. Results: We found circulating Metrnl levels were significantly decreased in patients with ACS as compared to healthy controls. Metrnl were inversely associated with the incident and recurrent risk of acute coronary syndrome after adjustment for traditional risk factors. Metrnl inhibition in HFD-fed ApoE-/- mice resulted in aggravated atherosclerotic lesions with an SMC-poor/macrophage-rich fibrous cap. Further study demonstrated that Metrnl downregulation increased whereas overexpression prevented SMCs apoptosis and lipid trans-differentiation. KIT/SRC/AKT signaling pathway is involved in the role of Metrnl for the regulation of SMCs fate. Conclusions: Our findings demonstrated that decreased circulating Metrnl levels might be a potential biomarker for identification of patients with increased risk of acute coronary syndrome. Metrnl protected against apoptosis and lipid trans-differentiation in SMCs and stabilized the atherosclerotic plaque, suggesting a potential target for the treatment of atherosclerosis.