Vascular
inflammation initiated by oxidized
lipoproteins drives initiation, progression, and even
rupture of
atherosclerotic plaques. Yet, to date, no
biomarker is directly linked to oxidized
lipid-induced vascular
inflammation.
Reticulocalbin 2 (RCN2) is a key regulator of basal and oxidized
lipid-induced
cytokine production in arterial wall cells. We evaluated the potential of circulating RCN2 to identify subjects with or at risk of developing
atherosclerosis. Immunohistochemical analysis revealed abundant RCN2 expression in the endothelium and adventitia of normal arteries and in atherosclerotic lesions of both humans and mice.
Atherosclerosis-susceptible C57BL/6 (B6) mice had higher plasma Rcn2 levels than resistant C3H mice. High-fat diet feeding raised plasma Rcn2 levels of both strains. In humans, patients with
coronary artery disease (CAD) or
peripheral artery disease (PAD) showed elevated serum RCN2 levels compared to healthy controls. In a cohort of 92 CAD patients, serum RCN2 exhibited a significant inverse correlation with
HDL cholesterol and K+ levels and a trend toward association with white blood cell account, Na+,
statin treatment, and diastolic blood pressure. HDL treatment suppressed Rcn2 expression in endothelial cells. This study suggests that circulating RCN2 is a potential non-invasive
biomarker for identifying individuals with
atherosclerosis and HDL protects against
atherosclerosis by downregulation of RCN2 expression in endothelial cells.