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.