on May 1, 2003
Published online before print May 1, 2003, doi: 10.1161/01.ATV.0000074899.60898.FD
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Submitted on March 21, 2003
Accepted on April 22, 2003
Increased Serum Levels of Heat Shock Protein 70 Are Associated With Low Risk of Coronary Artery Disease
Jianhui Zhu *;
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.
* To whom correspondence should be addressed. 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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