Skip to main content
SpringerLink
Log in
Book cover

General Methods in Biomarker Research and their Applications pp 757–781Cite as

Serum Heat Shock Proteins as Novel Biomarker for Heart Failure and Cardiovascular Diseases

  • Reference work entry
  • First Online:

  • 2389 Accesses

Abstract

Heat shock proteins (HSPs) or chaperonins, as they were previously named, are a group of evolutionarily conserved proteins that show high sequence homology between different species, from bacteria to humans (Morimoto. Science. 1993;259:1409–10). They are involved in maintaining various cellular proteins in their correctly folded functional forms (Patterson and Cyr. Circulation. 2002;106:2741–6). These proteins have several functions such as cytoprotection and intracellular assembly, stabilization, folding, and translocation of oligomeric proteins (Hightower. Cell 1991;66:191–7). In particular, heat shock protein 60 (HSP60) is a mitochondrial protein constitutively expressed in the majority of cells, and its expression is upregulated by a variety of stressors. In the setting of cardiovascular disease, higher titers of antibody to HSPs have been reported in atherosclerosis, which may contribute to immunoactivation in this process and other similar conditions. In heart failure, HSP60 is released from cardiomyocytes; it has been demonstrated in several studies that increased serum HSP60 is related to the severity of the disease. In fact, high levels of sHSP60 correlate with worse prognosis and higher mortality rate in patients with acute heart failure (AHF) (Bonanad et al. Congest Heart Fail. 2013;19:6–10).

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   399.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

AHF:

Acute Heart Failure

CHD:

Coronary Heart Disease

CHF:

Chronic Heart Failure

ELISA:

Enzyme-Linked Immunosorbent Assay

HF:

Heart Failure

HPSs:

Heat Shock Proteins

HR:

Heart Rate

IQR:

Interquartile Range

LVEF:

Left Ventricular Ejection Fraction

sHSP60:

Serum Heat Shock Protein 60

T:

Tertile

TLR4:

Toll-like Receptor 4

References

  • Acunzo J, Katsogiannou M, Rocchi P. Small heat shock proteins HSP27 (HspB1), αB-crystallin (HspB5) and HSP22 (HspB8) as regulators of cell death. Int J Biochem Cell Biol. 2012;44:1622–31. doi:10.1016/j.biocel.2012.04.002.

    Article  CAS  PubMed  Google Scholar 

  • Amberger A, Maczek C, Jürgens G, Michaelis D, Schett G, Trieb K, et al. Co-expression of ICAM-1, VCAM-1, ELAM-1 and Hsp60 in human arterial and venous endothelial cells in response to cytokines and oxidized low-density lipoproteins. Cell Stress Chaperones. 1997;2:94–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Antonova G, Lichtenbeld H, Xia T, Chatterjee A, Dimitropoulou C, Catravas JD. Functional significance of hsp90 complexes with NOS and sGC in endothelial cells. Clin Hemorheol Microcirc. 2007;37:19–35.

    CAS  PubMed  Google Scholar 

  • Benjamin IJ, McMillan DR. Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease. Circ Res. 1998;83:117–32.

    Article  CAS  PubMed  Google Scholar 

  • Birnie DH, Hood S, Holmes E, Hillis WS. Anti-heat shock protein 65 titres in acute myocardial infarction. Lancet. 1994;344:1443.

    Article  CAS  PubMed  Google Scholar 

  • Birnie D, McKay IC, Veitch J, Whaley K, Hood S, Hillis WS, et al. Antimycobacterial hsp65 and rheumatoid factor titres in a population of normal twins: evidence of genetic control of rheumatoid factor. Clin Exp Immunol. 1995;101:393–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Birnie DH, Holme ER, McKay IC, Hood S, McColl KE, Hillis WS. Association between antibodies to heat shock protein 65 and coronary atherosclerosis. Possible mechanism of action of Helicobacter pylori and other bacterial infections in increasing cardiovascular risk. Eur Heart J. 1998;19:387–94.

    Article  CAS  PubMed  Google Scholar 

  • Birnie DH, Vickers LE, Hillis WS, et al. Increased titres of anti-human heat shock protein 60 predict an adverse one year prognosis in patients with acute cardiac chest pain. Heart. 2005;91:1148–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonanad C, Núñez J, Sanchis J, Bodi V, Chaustre F, Chillet M, et al. Serum heat shock protein 60 in acute heart failure: a new biomarker? Congest Heart Fail. 2013;19:6–10. doi:10.1111/j.1751-7133.2012.00299.x.

    Article  CAS  PubMed  Google Scholar 

  • Davies KJ. Degradation of oxidized proteins by the 20S proteasome. Biochimie. 2001;83:301–10.

    Article  CAS  PubMed  Google Scholar 

  • George J, Afek A, Gilburd B, et al. Cellular and humoral immune responses to heat shock protein 65 are both involved in promoting fatty-streak formation in LDL-receptor deficient mice. J Am Coll Cardiol. 2001;38:900–5.

    Article  CAS  PubMed  Google Scholar 

  • Ghayour-Mobarhan M, New SA, Lamb DJ, Starkey BJ, Livingstone C, Wang T, et al. Dietary antioxidants and fat are associated with plasma antibody titers to heat shock proteins 60, 65, and 70 in subjects with dyslipidemia. Am J Clin Nutr. 2005;81:998–1004.

    CAS  PubMed  Google Scholar 

  • Goldberg AL. Protein degradation and protection against misfolded or damaged proteins. Nature. 2003;426:895–9.

    Article  CAS  PubMed  Google Scholar 

  • Gupta S, Knowlton AA. Cytosolic heat shock protein 60, hypoxia, and apoptosis. Circulation. 2002;106:2727–33.

    Article  CAS  PubMed  Google Scholar 

  • Gupta S, Knowlton AA. HSP60 trafficking in adult cardiac myocytes: role of the exosomal pathway. Am J Physiol Heart Circ Physiol. 2007;292:H3052–6.

    Article  CAS  PubMed  Google Scholar 

  • Hightower LE. Heat shock, stress proteins, chaperones and proteotoxicity. Cell. 1991;66:191–7.

    Article  CAS  PubMed  Google Scholar 

  • Hooper PL. Insulin signaling, GSK-3, heat shock proteins and the natural history of type 2 diabetes mellitus: a hypothesis. Metab Syndr Relat Disord. 2007;5(3):220–30. doi:10.1089/met.2007.0005.

    Article  CAS  PubMed  Google Scholar 

  • Kaufmann SHE. Heat shock proteins and the immune response. Immunol Today. 1990;11:129–36.

    Article  CAS  PubMed  Google Scholar 

  • Kirchhoff SR, Gupta S, Knowlton AA. Cytosolic heat shock protein 60, apoptosis, and myocardial injury. Circulation. 2002;105:2899–904.

    Article  CAS  PubMed  Google Scholar 

  • Knoflach M, Kiechl S, Kind M, Said M, Sief R, Gisinger M, et al. Cardiovascular risk factors and atherosclerosis in young males: ARMY study (Atherosclerosis Risk-Factors in Male Youngsters). Circulation. 2003;108:1064–9.

    Article  PubMed  Google Scholar 

  • Knoflach M, Bernhard D, Wick G. Anti-HSP60 immunity is already associated with atherosclerosis early in life. Ann N Y Acad Sci. 2005;1051:323–31.

    Article  CAS  PubMed  Google Scholar 

  • Knowlton AA, Kapadia S, Torre-Amione G, Durand JB, Bies R, Young J, et al. Differential expression of heat shock proteins in normal and failing human hearts. J Mol Cell Cardiol. 1998;30:811–8.

    Article  CAS  PubMed  Google Scholar 

  • Kreutmayer SB, Messner B, Knoflach M, Henderson B, Niederegger H, Böck G, et al. Dynamics of heat shock protein 60 in endothelial cells exposed to cigarette smoke extract. J Mol Cell Cardiol. 2011;51:777–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Song Y, Xing R, Yu H, Zhang Y, Li Z, et al. Heat shock protein 70 acts as a potential biomarker for early diagnosis of heart failure. PLoS ONE. 2013;8:e67964. doi:10.1371/journal.pone.0067964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin KM, Lin B, Lian IY, Mestril R, Scheffer IE, Dillmann WH. Combined and individual mitochondrial HSP60 and HSP10 expression in cardiac myocytes protects mitochondrial function and prevents apoptotic cell deaths induced by simulated ischemia-reoxygenation. Circulation. 2001;103:1787–92.

    Article  CAS  PubMed  Google Scholar 

  • Lin L, Kim SC, Wang Y, Gupta S, Davis B, Simon SI, et al. HSP60 in heart failure: abnormal distribution and role in cardiac myocyte apoptosis. Am J Physiol Heart Circ Physiol. 2007;293:H2238–47.

    Article  CAS  PubMed  Google Scholar 

  • Marunouchi T, Abe Y, Murata M, Inomata S, Sanbe A, Takagi N, et al. Changes in small heat shock proteins HSPB1, HSPB5 and HSPB8 in mitochondria of the failing heart following myocardial infarction in rats. Biol Pharm Bull. 2013;36:529–39.

    Article  CAS  PubMed  Google Scholar 

  • Mayr M, Metzler B, Kiechl S, Willeit J, Schett G, Xu Q, et al. Endothelial cytotoxicity mediated by serum antibodies to heat shock proteins of Escherichia coli and Chlamydia pneumonia. Immune reactions to heat shock proteins as a possible link between infection and atherosclerosis. Circulation. 1999;99:1560–6.

    Article  CAS  PubMed  Google Scholar 

  • Millonig G, Schwentner C, Mueller P, Mayerl C, Wick G. The vascular-associated lymphoid tissue: a new site of local immunity. Curr Opin Lipidol. 2001;12:547–53.

    Article  CAS  PubMed  Google Scholar 

  • Millonig G, Malcom GT, Wick G. Early inflammatory-immunological lesions in juvenile atherosclerosis from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY)-study. Atherosclerosis. 2002;160:441–8.

    Article  CAS  PubMed  Google Scholar 

  • Morimoto RI. Cells in stress: transcriptional activation of heat shock genes. Science. 1993;259:1409–10.

    Article  CAS  PubMed  Google Scholar 

  • Niizeki T, Takeishi Y, Watanabe T, Nitobe J, Miyashita T, Miyamoto T, et al. Relation of serum heat shock protein 60 level to severity and prognosis in chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2008;102:606–10.

    Article  CAS  PubMed  Google Scholar 

  • Patterson C, Cyr D. Welcome to the machine: a cardiologist’s introduction to protein folding and degradation. Circulation. 2002;106:2741–6.

    Article  PubMed  Google Scholar 

  • Paulsson G, Zhou X, Törnquist E, Hansson GK. Oligoclonal T cell expansions in atherosclerotic lesions of apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2000;20:10–7.

    Article  CAS  PubMed  Google Scholar 

  • Pockley AG. Heat shock proteins, inflammation, and cardiovascular disease. Circulation. 2002;105:1012–7.

    Article  CAS  PubMed  Google Scholar 

  • Pockley AG, Frostegård J. Heat shock proteins in cardiovascular disease and the prognostic value of heat shock protein related measurements. Heart. 2005;91:1124–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pockley AG, Bulmer J, Hanks BM, Wright BH. Identification of human heat shock protein 60 (Hsp60) and anti-Hsp60 antibodies in the peripheral circulation of normal individuals. Cell Stress Chaperones. 1999;4:29–35.

    Article  CAS  PubMed  Google Scholar 

  • Pockley AG, Wu R, Lemne C, Kiessling R, de Faire U, Frostegård J. Circulating heat shock protein 60 is associated with early cardiovascular disease. Hypertension. 2000;36:303–7.

    Article  CAS  PubMed  Google Scholar 

  • Powell SR. The ubiquitin-proteasome system in cardiac physiology and pathology. Am J Physiol Heart Circ Physiol. 2006;291:H1–19.

    Article  CAS  PubMed  Google Scholar 

  • Rossmann A, Henderson B, Heidecker B, Seiler R, Fraedrich G, Singh M, et al. T-cells from advanced atherosclerotic lesions recognize hHSP60 and have a restricted T-cell receptor repertoire. Exp Gerontol. 2008;43:229–37. doi:10.1016/j.exger.2007.11.009.

    Article  CAS  PubMed  Google Scholar 

  • Saban KL, Hoppensteadt D, Bryant FB, Devon HA. Social determinants and heat shock protein-70 among african american and non-hispanic white women with atherosclerosis: a pilot study. Biol Res Nurs. 2013;16(3):258–265.

    Google Scholar 

  • Sanbe A, Marunouchi T, Abe T, Tezuka Y, Okada M, Aoki S, et al. Phenotype of cardiomyopathy in cardiac-specific heat shock protein B8 K141N transgenic mouse. J Biol Chem. 2013;288:8910–21. doi:10.1074/jbc.M112.368324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schett G, Xu Q, Amberger A, Van der Zee R, Recheis H, Willeit J, et al. Autoantibodies against heat shock protein 60 mediate endothelial cytotoxicity. J Clin Invest. 1995;96(6):2569–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seibert TA, Hibbert B, Chen YX, Rayner K, Simard T, Hu T, et al. Serum heat shock protein 27 levels represent a potential therapeutic target for atherosclerosis: observations from a human cohort and treatment of female mice. J Am Coll Cardiol. 2013. doi:10.1016/j.jacc.2013.05.041.

    PubMed  Google Scholar 

  • Shamaei-Tousi A, Stephens JW, Bin R, Cooper JA, Steptoe A, Coates AR, et al. Association between plasma levels of heat shock protein 60 and cardiovascular disease in patients with diabetes mellitus. Eur Heart J. 2006;27:1565–70.

    Article  CAS  PubMed  Google Scholar 

  • Shin YO, Bae JS, Lee JB, Kim JK, Kim YJ, Kim C, et al. Effect of cardiac rehabilitation and statin treatment on anti-HSP antibody titers in patients with coronary artery disease after percutaneous coronary intervention. Int Heart J. 2006;47:671–82.

    Article  CAS  PubMed  Google Scholar 

  • Wick G, Perschinka H, Millonig G. Atherosclerosis as an autoimmune disease: an update. Trends Immunol. 2001;22:665–9.

    Article  CAS  PubMed  Google Scholar 

  • Wick G, Knoflach M, Xu Q. Autoimmune and inflammatory mechanisms in atherosclerosis. Annu Rev Immunol. 2004;22:361–403.

    Article  CAS  PubMed  Google Scholar 

  • Xu Q. Role of heat shock proteins in atherosclerosis. Arterioscler Thromb Vasc Biol. 2002;22:1547–59.

    Article  CAS  PubMed  Google Scholar 

  • Xu Q, Wick G. The role of heat shock proteins in protection and pathophysiology of the arterial wall. Mol Med Today. 1996;2:372–9.

    Article  CAS  PubMed  Google Scholar 

  • Xu Q, Kleindienst R, Waitz W, Dietrich H, Wick G. Increased expression of heat shock protein 65 coincides with a population of infiltrating T lymphocytes in atherosclerotic lesions of rabbits specifically responding to heat shock protein 65. J Clin Invest. 1993a;91:2693–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu Q, Willeit J, Marosi M, Kleindienst R, Oberhollenzer F, Kiechl S, et al. Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis. Lancet. 1993b;341:255–9.

    Article  CAS  PubMed  Google Scholar 

  • Xu Q, Kiechl S, Mayr M, Metzler B, Egger G, Oberhollenzer F, et al. Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis: clinical significance determined in a follow-up study. Circulation. 1999;100:1169–74.

    Article  CAS  PubMed  Google Scholar 

  • Xu Q, Schett G, Perschinka H, Mayr M, Egger G, Oberhollenzer F, et al. Serum soluble heat shock protein 60 is elevated in subjects with atherosclerosis in a general population. Circulation. 2000;102:14–20.

    Article  CAS  PubMed  Google Scholar 

  • Young RA. Stress proteins and immunology. Ann Rev Immunol. 1990;8:401–20.

    Article  CAS  Google Scholar 

  • Zhang X, He M, Cheng L, Chen Y, Zhou L, Zeng H, et al. Elevated heat shock protein 60 levels are associated with higher risk of coronary heart disease in Chinese. Circulation. 2008;118:2687–93.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Servicio de Cardiología, Hospital Clínic Universitari, INCLIVA. Universidad de Valencia, Valencia, Spain

    Clara Bonanad, Sergio García-Blas, Paolo Racugno, Silvia Ventura, Fabian Chaustre & Julio Núñez

Authors
  1. Clara Bonanad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sergio García-Blas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paolo Racugno
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Silvia Ventura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fabian Chaustre
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Julio Núñez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clara Bonanad .

Editor information

Editors and Affiliations

  1. Department of Nutrition and Dietetics, Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom

    Victor R. Preedy

  2. Faculty of Science & Technology, Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Bonanad, C., García-Blas, S., Racugno, P., Ventura, S., Chaustre, F., Núñez, J. (2015). Serum Heat Shock Proteins as Novel Biomarker for Heart Failure and Cardiovascular Diseases. In: Preedy, V., Patel, V. (eds) General Methods in Biomarker Research and their Applications. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7696-8_13

Download citation

Publish with us

Policies and ethics

Search

Navigation