RELM-α reduces diabetic atherosclerosis in LDLR knockout mice

Abstract

Resistin-like molecule (RELM)-α belongs to a family of secreted mammalian proteins that have putative immunomodulatory functions. Recent studies have identified a role of RELM-α in the pathogenesis of hyperlipidemia-induced atherosclerosis. However, whether RELM-α regulates diabetic atherosclerosis is unknown. Here we report that RELM-α has anti-atherogenic effects and protects against diabetic atherosclerosis in low-density lipoprotein receptor-deficient mice (LDLR -/-). Severity of the induced diabetic state was confirmed by monitoring of blood glucose levels and body weight. RELM-α overexpression appears to have a cholesterol-lowering effect. In particular, there was significant difference in cholesterol levels of diabetic group. After 8 weeks on a High-fat diet (HFD), total en face aortic lesion area was reduced in RELM-α overexpressing (RELM-α Tg) mice compared with control mice in both non-diabetic and diabetic group. Plaque area in the aortic arch was also decreased in RELM-α Tg of both groups. We show RELM-α overexpression has a higher anti-atherogenic effect with decrease of cholesterol in diabetic atherosclerosis compared with non-diabetic group. These findings define RELM-α as a novel therapeutic target for treating diabetic atherosclerosis.