Early atherosclerosis and vascular inflammation in mice with diet-induced type 2 diabetes.
BACKGROUND
Obesity and type 2 diabetes increase the risk of atherosclerosis. It is unknown to what extent this reflects direct effects on the arterial wall or secondary effects of hyperlipidaemia.


METHODS
The effect of obesity and type 2 diabetes on the development of atherosclerosis and inflammation, in the absence or presence of hyperlipidaemia, was assed in wild-type (n = 36) and human apolipoprotein B (apoB) transgenic mice (n = 27) that were fed normal chow or 60% fat for 12 months.


RESULTS
Fat-feeding caused obesity, glucose intolerance and elevated plasma leptin and soluble vascular cell adhesion molecule-1 (sVCAM-1) in both wild-type and apoB transgenic mice. In wild-type mice, plasma very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) were unaffected by fat-feeding. ApoB transgenic mice had mildly elevated plasma LDL-C (approximately 1 mmol L(-1)), which was slightly increased by fat-feeding. Sixty-four per cent of fat-fed wild-type mice vs. 7% of chow-fed wild-type mice had lipid-staining intimal lesions in the aortic root (P = 0.002). Eighty-six per cent of fat-fed apoB transgenic mice had lipid-staining lesions and the median lesion area was 8.0 times higher than in fat-fed wild-type mice (P = 0.001). Intracellular adhesion molecule-1 staining of the aortic endothelium was most pronounced in the fat-fed apoB transgenic mice.


CONCLUSIONS
Our findings suggest that diet-induced type 2 diabetes causes early atherosclerosis in the absence of dyslipidaemia, and that even a moderate level of LDL-C markedly augments this effect.
Bartels
E D
ED
Rigshospitalet, University Hospital of Copenhagen and University of Copenhagen, Copenhagen, Denmark. emil.daniel.bartels@rh.regionh.dk
Bang
C A
CA
Nielsen
L B
LB
D000818:Animals; D001167:Arteritis / Q000209:etiology* / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D003925:Diabetic Angiopathies / Q000209:etiology*; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications; D020738:Leptin / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000150:complications*; D011897:Random Allocation; D012307:Risk Factors; D013223:Statistics as Topic; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D004041:Dietary Fats; D020738:Leptin; D019010:Vascular Cell Adhesion Molecule-1