Relationship between plasma cholesterol, von Willebrand factor concentrations, extent of atherosclerosis and antibody titres to heat shock proteins-60, -65 and -70 in cholesterol-fed rabbits.
Epidemiological studies have shown an association between atherosclerosis, Heat shock protein (Hsp) expression, and Hsp antibody titres. We aimed to investigate the time course of appearance of Hsp-60, -65 and -70 antibodies in the cholesterol-fed rabbit and to relate antibody titres to serum concentrations of von Willebrand factor (vWF), a marker of endothelial injury. Rabbits were fed with 0.25-1.0% cholesterol diet for 13 weeks. Plasma levels of anti Hsp-60, -65 and -70 IgG titres, were measured using in-house enzyme-linked immunosorbent assays (ELISAs) together with plasma vWF concentrations. Plasma titres of anti-Hsp-60, -65 and -70 antibodies were all significantly increased by weeks 5, 7 and 9 following commencement of the experimental diet compared with baseline (P < 0.05 for all). In non-cholesterol-fed rabbits, plasma levels of anti-Hsp titres were unchanged over this period. Increased plasma vWF concentrations were also found in the cholesterol-fed rabbits, reaching a maximum at approximately week 8, and falling thereafter. Furthermore, plasma vWF concentrations at 13 weeks correlated strongly with antibody titres to all three Hsps (r = 0.90, P = 0.002; r = 0.80, P = 0.017; r = 0.86, P = 0.006 for Hsp 60, -65 and -70 respectively) and titres were also strongly correlated with final plasma cholesterol concentrations in cholesterol-fed animals (r = 0.95, P = 0.002; r = 0.8, P = 0.001; r = 0.84, P = 0.01 respectively). In cholesterol-fed rabbits, antibody titres to Hsp-60, -65 and -70 appear to rise in association with a marker of endothelial injury, peaking at approximately the same time (8 weeks) after starting a high cholesterol diet.
Ghayour-Mobarhan
Majid
M
Centre for Clinical Science and Measurement, School of Biomedical and Molecular Science, University of Surrey, Guildford, Surrey, UK.
Lamb
David J
DJ
Tavallaie
Shima
S
Ferns
Gordon A A
GA
D000818:Animals; D001013:Aorta, Thoracic; D001018:Aortic Diseases / Q000097:blood / Q000209:etiology / Q000276:immunology; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D018834:Chaperonin 60 / Q000276:immunology; D002784:Cholesterol / Q000097:blood*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology*; D011817:Rabbits; D014841:von Willebrand Factor / Q000378:metabolism*
D001323:Autoantibodies; D015415:Biomarkers; D018834:Chaperonin 60; D002791:Cholesterol, Dietary; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D014841:von Willebrand Factor; D002784:Cholesterol
Circulation. 1999 Sep 14;100(11):1169-74
10484536
Atherosclerosis. 1999 Mar;143(1):105-13
10208485
Am J Clin Nutr. 2005 May;81(5):998-1004
15883421
Scand J Clin Lab Invest. 2005;65(7):601-14
16271992
Acute Card Care. 2006;8(1):46-50
16720428
Toxicol Pathol. 2000 Sep-Oct;28(5):688-93
11026604
Circulation. 2001 Feb 27;103(8):1071-5
11222468
Circulation. 2001 Mar 20;103(11):1503-8
11257076
Scand J Clin Lab Invest. 2001 Jul;61(4):317-23
11465346
Atherosclerosis. 2002 Dec;165(2):231-40
12417273
Circulation. 2002 Nov 26;106(22):2775-80
12451002
Atherosclerosis. 2003 Apr;167(2):177-85
12818399
Hypertension. 2003 Sep;42(3):235-8
12900429
Lancet. 1975 Jun 28;1(7922):1430
49599
Ann Intern Med. 1981 Apr;94(4 pt 1):482-4
6782927
Thromb Res. 1983 Jun 1;30(5):487-97
6412388
Lancet. 1993 Jan 30;341(8840):255-9
8093914
J Clin Invest. 1993 Feb;91(2):465-73
8094399
Science. 1993 Mar 5;259(5100):1409-10
8451637
Diabetes. 1995 May;44(5):561-4
7729616
Int J Exp Pathol. 1997 Feb;78(1):21-32
9166102
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10425-30
9724719
Arterioscler Thromb Vasc Biol. 1998 Sep;18(9):1359-62
9743222
N Engl J Med. 1999 Jan 14;340(2):115-26
9887164
Arterioscler Thromb Vasc Biol. 1999 Oct;19(10):2524-34
10521383