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Plasma levels of Hsp70 and anti-Hsp70 antibody predict risk of acute coronary syndrome

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Cell Stress and Chaperones Aims and scope

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Abstract

Although immune reactions against heat shock proteins have been implicated in the pathogenesis of atherosclerosis, conflicting associations between Hsp70, anti-Hsp70 antibody and coronary heart disease (CHD) have been reported. This study assessed whether there is a significant association between extracellular human Hsp70, anti-Hsp70 antibody and acute coronary syndrome (ACS) and stable angina (SA), and examined dynamic changes in Hsp70 and anti-Hsp70 antibody levels induced by acute myocardial infarction (AMI). Plasma Hsp70 and anti-Hsp70 antibody levels in 291 patients with ACS (179 AMI, 112 unstable angina), 126 patients with SA and 417 age and sex-matched healthy subjects, and in 40 patients after admission for AMI, and on day 2, 3, and 7 after the onset of AMI were determined using enzyme-linked immunosorbent assays. Hsp70 levels were significantly higher in ACS and SA and anti-Hsp70 antibody levels were only markedly lower in ACS than controls. After adjustment for traditional CHD risk factors, increasing levels of Hsp70 were significantly associated with an increased risk and severity of ACS (P for trend < 0.001), whereas increasing levels of anti-Hsp70 antibody were associated with a decreased risk of ACS (P for trend = 0.0003). High levels of Hsp70 combined with low levels of anti-Hsp70 antibody had a joint effect on the risk of ACS (OR, 5.14, 95% CI, 3.00-8.79; P < 0.0001). In patients with AMI, Hsp70 levels decreased rapidly from days 1-7 after onset, whereas anti-Hsp70 antibody levels increased in patients with AMI. These findings suggest that higher Hsp70 levels or lower anti-Hsp70 antibody levels are independently associated with a higher risk of ACS. Higher Hsp70 levels and lower anti-Hsp70 antibody levels combine to further increase this risk.

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Abbreviations

Hsps:

heat shock proteins

CHD:

coronary heart disease

ACS:

acute coronary syndrome

SA:

stable angina

AMI:

acute myocardial infarction

UA:

unstable angina

CKMB:

creatine phosphokinase MB

cTNI:

cardiac troponin I

BMI:

body mass index

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Acknowledgments

We are particularly grateful to all CHD patients and volunteers for participating in the present study and to the medical personnel of Tongji Hospital, Union Hospital, Wugang Hospital, Wuhan Second Hospital, and Dr Tangchun Wu’s lab in Wuhan City, Hubei Province, China for their kind assistance in collecting the data and samples. We also thank A. Graham Pockley (University of Sheffield, Sheffield, UK) for his critical review of this manuscript. This work was supported by research funds from the National Natural Scientific Foundation of China (NNSFC 30430590 and 30525031 to Tangchun Wu) and a China-Canada collaborative research grant of the Canadian Institutes of Health Research (CIHR, CCI85673, Robert M Tanguay) and NNSFC (30711120579, Tangchun Wu).

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Authors and Affiliations

  1. Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, Hubei, 430030, China

    Xiaomin Zhang, Zengguang Xu, Li Zhou, Meian He & Tangchun Wu

  2. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 32 Xinhua Rd, Wuhan, Hubei, 430030, China

    Ying Chen & Longxian Cheng

  3. Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA

    Frank B. Hu

  4. Laboratory of Cellular and Developmental Genetics, Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine and IBIS, Pavillion C.E. Marchand, Université Laval, Québec, Canada, G1V 0A6

    Robert M. Tanguay

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  1. Xiaomin Zhang
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  2. Zengguang Xu
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  3. Li Zhou
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  4. Ying Chen
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  5. Meian He
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  6. Longxian Cheng
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  7. Frank B. Hu
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  8. Robert M. Tanguay
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  9. Tangchun Wu
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Correspondence to Tangchun Wu.

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Zhang, X., Xu, Z., Zhou, L. et al. Plasma levels of Hsp70 and anti-Hsp70 antibody predict risk of acute coronary syndrome. Cell Stress and Chaperones 15, 675–686 (2010). https://doi.org/10.1007/s12192-010-0180-3

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  • DOI: https://doi.org/10.1007/s12192-010-0180-3

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