Effect of uremia on HDL composition, vascular inflammation, and atherosclerosis in wild-type mice.
Wild-type mice normally do not develop atherosclerosis, unless fed cholic acid. Uremia is proinflammatory and increases atherosclerosis 6- to 10-fold in apolipoprotein E-deficient mice. This study examined the effect of uremia on lipoproteins, vascular inflammation, and atherosclerosis in wild-type C57BL/6J mice. Uremia was induced by nephrectomy (NX) and increased plasma urea and creatinine concentrations 2.5- to 4.5-fold; control mice were sham operated. After NX, mice were fed a Western-type diet or the same diet with 0.5% cholic acid. Cholic acid-fed NX mice did not thrive and were killed. In NX mice fed the Western-type diet (n = 7), the total plasma cholesterol concentration was similar to that in sham mice (n = 11), but on gel filtration the LDL/HDL cholesterol ratio was increased. HDL from NX mice contained more serum amyloid A and triglycerides and less cholesterol than HDL from sham mice. Plasma concentrations of sICAM-1 and sVCAM-1 and aortic mRNA expression of ICAM-1 and VCAM-1 did not differ between NX and sham mice. Twenty-six weeks after NX, the average oil red O-stained area of the aortic root was similar in NX and sham mice fed the Western-type diet, while it was increased in cholic acid-fed sham mice. The results suggest that moderate uremia neither induces aortic inflammation nor atherosclerosis in C57BL/6J mice despite increased LDL/HDL cholesterol ratio and altered HDL composition.
Bang
Christian A
CA
Department of Clinical Biochemistry, University of Copenhagen, Copenhagen, Denmark.
Bro
Susanne
S
Bartels
Emil D
ED
Pedersen
Tanja X
TX
Nielsen
Lars B
LB
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism; D050197:Atherosclerosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002791:Cholesterol, Dietary / Q000009:adverse effects / Q000494:pharmacology; D019826:Cholic Acid / Q000009:adverse effects / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009392:Nephrectomy; D012333:RNA, Messenger / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism; D014511:Uremia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014657:Vasculitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D002791:Cholesterol, Dietary; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019826:Cholic Acid