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 (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.
Free Radical Group, Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia; Faculty of Medicine, University of Sydney, NSW 2006, Australia. Electronic address: brownb@hri.org.au.
Bronwyn E
BE
Brown
Free Radical Group, Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia. Electronic address: christinehjkim@gmail.com.
Christine H J
CH
Kim
School of the Environment, University of Technology, Sydney, PO Box 123, Broadway, NSW 2007, Australia. Electronic address: Fraser.Torpy@uts.edu.au.
Fraser R
FR
Torpy
Immunobiology Group, Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia. Electronic address: bursillc@hri.org.au.
Christina A
CA
Bursill
Gene Regulation Group, Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia. Electronic address: l.mcrobb@unsw.edu.au.
Lucinda S
LS
McRobb
Gene Regulation Group, Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia; School of Medical and Molecular Biosciences, University of Technology, Sydney, PO Box 123, Broadway, NSW 2007, Australia. Electronic address: alison.heather@uts.edu.au.
Alison K
AK
Heather
Free Radical Group, Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia; Faculty of Medicine, University of Sydney, NSW 2006, Australia. Electronic address: daviesm@hri.org.au.
Michael J
MJ
Davies
School of Medical and Molecular Biosciences, University of Technology, Sydney, PO Box 123, Broadway, NSW 2007, Australia. Electronic address: david.vanreyk@uts.edu.au.
David M
DM
van Reyk
D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D016122:Brachiocephalic Trunk / Q000473:pathology; D002336:Carnosine / Q000627:therapeutic use*; D002784:Cholesterol / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D019587:Dietary Supplements; D006454:Hemoglobins / Q000378:metabolism; D015228:Hypertriglyceridemia / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015999:Multivariate Analysis; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000628:therapy*; D014280:Triglycerides / Q000097:blood*
D001057:Apolipoproteins E; D001786:Blood Glucose; D006454:Hemoglobins; D014280:Triglycerides; D002336:Carnosine; D002784:Cholesterol
Atherosclerosis; Carnosine; Cholesterol; Diabetes; Triglycerides