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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1055.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Increased Serum Levels of Heat Shock Protein 70 Are Associated With Low Risk of Coronary Artery Disease

Jianhui Zhu; Arshed A. Quyyumi; Hongsheng Wu; Gyorgy Csako; David Rott; Alexandra Zalles-Ganley; Jibike Ogunmakinwa; Julian Halcox; Stephen E. Epstein

From the Cardiovascular Research Institute (J.Z., H.W., D.R., A.Z.-G., J.O., S.E.E.), MedStar Research Institute, Washington Hospital Center, Washington, DC; Division of Cardiology (A.A.Q.), Emory University Hospital, Atlanta, Ga; Clinical Center (G.C.), National Institutes of Health, Bethesda, Md; and Cardiology Branch (J.H.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.

Correspondence to Dr Jianhui Zhu, Cardiovascular Research Institute, Washington Hospital Center, 108 Irving St NW, GHRB Room 217, Washington, DC 20010. E-mail jianhui.zhu{at}medstar.net

Objective— Previous studies suggest that heat shock protein (HSP) 60 has a contributory role in atherosclerosis development. We examined whether circulating HSP70 protein and anti-HSP70 antibodies are associated with coronary artery disease (CAD).

Methods and Results— Blood samples from 421 patients (62% men, mean age 57 years) evaluated for CAD by coronary angiography were tested. Serum HSP70 was detectable in 67% of study subjects with levels ranging from 0.2 to 27.1 ng/mL (mean, 1.08; median, 0.5). HSP70 levels were higher in non-CAD patients than CAD patients (median, 0.72 versus 0.34; P=0.0006). Individuals with HSP70 levels above the median (0.5 ng/mL) had half the risk of CAD than individuals with levels below the median (adjusted odds ratio, 0.52; 95% confidence limit, 0.32 to 0.86). The association of high HSP70 levels with low CAD risk was independent of traditional CAD risk factors (P=0.011). Disease severity (number of diseased vessels) was also inversely associated with HSP70 protein levels (P=0.010). The adjusted odds ratio of having multivessel disease for patients with high HSP70 protein levels was 0.54 (95% confidence limit, 0.36 to 0.81). In contrast, no association between anti-HSP70 IgG seropositivity and the prevalence of CAD was found (P=0.916).

Conclusions— These data provide the first evidence that high levels of human HSP70 are associated with the low CAD risk, probably through its multiple protective effects on a cell’s response to stress.

Key Words: coronary artery disease • heat shock protein • antibodies • protective effect

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