Supplementation with carnosine decreases plasma triglycerides and modulates atherosclerotic plaque composition in diabetic apo E-/- mice

Objective: Carnosine has been shown to modulate triglyceride and glycation levels in cell and animal systems. In this study we investigated whether prolonged supplementation with carnosine inhibits atherosclerosis and markers of lesion stability in hyperglycaemic and hyperlipidaemic mice. Methods: Streptozotocin-induced diabetic apo E-/- mice were maintained for 20 weeks, post-induction of diabetes. Half of the animals received carnosine (2 g/L) in their drinking water. Diabetes was confirmed by significant increases in blood glucose and glycated haemoglobin, plasma triglyceride and total cholesterol levels, brachiocephalic artery and aortic sinus plaque area; and lower body mass. Results: Prolonged carnosine supplementation resulted in a significant (similar to 20-fold) increase in plasma carnosine levels, and a significant (similar to 23%) lowering of triglyceride levels in the carnosine-supplemented groups regardless of glycaemic status. Supplementation did not affect glycaemic status, blood cholesterol levels or loss of body mass. In the diabetic mice, carnosine supplementation did not diminish measured plaque area, but reduced the area of plaque occupied by extracellular lipid (similar to 60%) and increased both macrophage numbers (similar to 70%) and plaque collagen content (similar to 50%). The area occupied by a-actin-positive smooth muscle cells was not significantly increased. Conclusions: These data indicate that in a well-established model of diabetes-associated atherosclerosis, prolonged carnosine supplementation enhances plasma levels, and has novel and significant effects on atherosclerotic lesion lipid, collagen and macrophage levels. These data are consistent with greater lesion stability, a key goal in treatment of existing cardiovascular disease. Carnosine supplementation may therefore be of benefit in lowering triglyceride levels and suppressing plaque instability in diabetes-associated atherosclerosis. (C) 2013 Elsevier Ireland Ltd. All rights reserved.