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

TY - JOUR

T1 - Supplementation with carnosine decreases plasma triglycerides and modulates atherosclerotic plaque composition in diabetic apo E(-/-) mice

AU - Brown, Bronwyn E

AU - Kim, Christine H J

AU - Torpy, Fraser R

AU - Bursill, Christina A

AU - McRobb, Lucinda S

AU - Heather, Alison K

AU - Davies, Michael Jonathan

AU - van Reyk, David M

N1 - Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

PY - 2014/2

Y1 - 2014/2

N2 - 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 (2g/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 (∼20-fold) increase in plasma carnosine levels, and a significant (∼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 (∼60%) and increased both macrophage numbers (∼70%) and plaque collagen content (∼50%). The area occupied by α-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.

AB - 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 (2g/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 (∼20-fold) increase in plasma carnosine levels, and a significant (∼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 (∼60%) and increased both macrophage numbers (∼70%) and plaque collagen content (∼50%). The area occupied by α-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.

KW - Animals

KW - Aorta

KW - Apolipoproteins E

KW - Blood Glucose

KW - Brachiocephalic Trunk

KW - Carnosine

KW - Cholesterol

KW - Diabetes Mellitus, Experimental

KW - Dietary Supplements

KW - Hemoglobins

KW - Hypertriglyceridemia

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Multivariate Analysis

KW - Plaque, Atherosclerotic

KW - Triglycerides

U2 - 10.1016/j.atherosclerosis.2013.11.068

DO - 10.1016/j.atherosclerosis.2013.11.068

M3 - Journal article

C2 - 24468155

SN - 0021-9150

VL - 232

SP - 403

EP - 409

JO - Atherosclerosis

JF - Atherosclerosis

IS - 2

ER -