Manganese supplementation reduces monocyte adhesion to endothelial cells by reducing ROS and downregulating ICAM‐1 independently of MnSOD

Abstract

Manganese (Mn2+ ) levels have been found to be lower in the plasma and lymphocytes of diabetic patients and in the heart and aortic tissue of patients with atherosclerosis. Studies in our laboratory have shown that Zucker diabetic fatty rats (ZDF) supplemented with Mn2+ had lower cholesterol (25%, p<0.05), ICAM‐1 (17%, p<0.04), and higher adiponectin (38%, p<0.01) levels in blood. Cell culture studies with Human Umbilical Vein Endothelial Cells (HUVECs) showed that Mn2+ supplementation reduces adhesion of monocytes to endothelial cells (ECs). This study examines the mechanisms by which Mn2+ supplementation decreases monocyte adhesion to ECs, a key event in the development of atherosclerosis. HUVECs were treated with Mn2+ (0, 5, 10 μM) for 24 hours, then exposed to high glucose (HG, 25 mM) for another 24 hrs. Results demonstrate that Mn2+ supplementation decreases ICAM‐1 surface (20%, p<0.05) and total expression (65%, p<0.005), MCP‐1 secretion (16%, p<0.05), and ROS levels (21%, p<0.02) in HG‐treated HUVECs. Silencing studies using siRNA against MnSOD showed that similar effects of Mn2+ on ICAM‐1 expression and ROS were observed in MnSOD knockdown HUVECs. This study suggests that Mn2+ supplementation can decrease monocyte adhesion to ECs, and thereby delay progression of atherosclerosis in diabetes, by decreasing ROS, MCP‐1 secretion, and ICAM‐1 expression, independently of MnSOD.Grant Funding Source: NIDDK and Office of Dietary Supplements