Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Association of elevated serum heat-shock protein 70 concentration with transient hypertension of pregnancy, preeclampsia and superimposed preeclampsia: a case–control study

Journal of Human Hypertension volume 20, pages 780–786 (2006)Cite this article

Abstract

Our aim was to investigate the association between serum heat-shock protein (Hsp) 70 concentration and hypertensive disorders of pregnancy. One hundred and forty-two pregnant women with hypertensive disorders (93 with preeclampsia, 29 with transient hypertension of pregnancy and 20 with superimposed preeclampsia) and 127 normotensive, healthy pregnant women were included in the study. Serum Hsp70 concentration was measured using enzyme-linked immunosorbent assay. The serum Hsp70 concentration was significantly higher in patients with transient hypertension of pregnancy, in preeclamptic patients and in patients with superimposed preeclampsia than in the control group (median (25–75 percentile): 0.66 (0.52–0.84), 0.55 (0.42–0.80), 0.61 (0.42–0.91) ng/ml vs 0.31 (0.27–0.39) ng/ml, respectively; P<0.001). Multivariate logistic regression analysis showed independent association of elevated serum Hsp70 level with transient hypertension of pregnancy, preeclampsia and superimposed preeclampsia. The difference in serum Hsp70 concentration between preeclamptic patients and the control group was statistically significant in each gestational age category. In the groups of preeclamptic and superimposed preeclamptic patients, there was no significant difference in serum Hsp70 concentration between mild and severe preeclamptic patients, between patients with late and early onset of the disease, as well as between preeclamptic patients without and with foetal growth restriction. In conclusion, serum Hsp70 concentration is elevated in transient hypertension of pregnancy, in preeclampsia and in superimposed preeclampsia. Circulating Hsp70 may not only be a marker for these conditions, but might also play a role in their pathogenesis. However, further studies are needed to explore its role in the pathogenesis of hypertensive disorders of pregnancy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Prohaszka Z, Fust G . Immunological aspects of heat-shock proteins – the optimum stress of life. Mol Immunol 2004; 41 (1): 29–44.

    Article  CAS  Google Scholar 

  2. Multhoff G, Hightower LE . Cell surface expression of heat shock proteins and the immune response. Cell Stress Chaperones 1996; 1 (3): 167–176.

    Article  CAS  Google Scholar 

  3. Soltys BJ, Gupta RS . Cell surface localization of the 60 kDa heat shock chaperonin protein (hsp60) in mammalian cells. Cell Biol Int 1997; 21 (5): 315–320.

    Article  CAS  Google Scholar 

  4. Hightower LE, Guidon Jr PT . Selective release from cultured mammalian cells of heat-shock (stress) proteins that resemble glia–axon transfer proteins. J Cell Physiol 1989; 138 (2): 257–266.

    Article  CAS  Google Scholar 

  5. Bassan M, Zamostiano R, Giladi E, Davidson A, Wollman Y, Pitman J et al. The identification of secreted heat shock 60-like protein from rat glial cells and a human neuroblastoma cell line. Neurosci Lett 1998; 250 (1): 37–40.

    Article  CAS  Google Scholar 

  6. Child DF, Williams CP, Jones RP, Hudson PR, Jones M, Smith CJ . Heat shock protein studies in type 1 and type 2 diabetes and human islet cell culture. Diabet Med 1995; 12 (7): 595–599.

    Article  CAS  Google Scholar 

  7. Liao DF, Jin ZG, Baas AS, Daum G, Gygi SP, Aebersold R et al. Purification and identification of secreted oxidative stress-induced factors from vascular smooth muscle cells. J Biol Chem 2000; 275 (1): 189–196.

    Article  CAS  Google Scholar 

  8. 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 (1): 29–35.

    Article  CAS  Google Scholar 

  9. Pockley AG, Shepherd J, Corton JM . Detection of heat shock protein 70 (Hsp70) and anti-Hsp70 antibodies in the serum of normal individuals. Immunol Invest 1998; 27 (6): 367–377.

    Article  CAS  Google Scholar 

  10. Rea IM, McNerlan S, Pockley AG . Serum heat shock protein and anti-heat shock protein antibody levels in aging. Exp Gerontol 2001; 36 (2): 341–352.

    Article  CAS  Google Scholar 

  11. Lewthwaite J, Owen N, Coates A, Henderson B, Steptoe A . Circulating human heat shock protein 60 in the plasma of British civil servants: relationship to physiological and psychosocial stress. Circulation 2002; 106 (2): 196–201.

    Article  CAS  Google Scholar 

  12. Xu Q, Li DG, Holbrook NJ, Udelsman R . Acute hypertension induces heat-shock protein 70 gene expression in rat aorta. Circulation 1995; 92 (5): 1223–1229.

    Article  CAS  Google Scholar 

  13. Kunes J, Poirier M, Tremblay J, Hamet P . Expression of hsp70 gene in lymphocytes from normotensive and hypertensive humans. Acta Physiol Scand 1992; 146 (3): 307–311.

    Article  CAS  Google Scholar 

  14. Wright BH, Corton JM, El Nahas AM, Wood RF, Pockley AG . Elevated levels of circulating heat shock protein 70 (Hsp70) in peripheral and renal vascular disease. Heart Vessels 2000; 15 (1): 18–22.

    Article  CAS  Google Scholar 

  15. Pockley AG, Wu R, Lemne C, Kiessling R, de Faire U, Frostegard J . Circulating heat shock protein 60 is associated with early cardiovascular disease. Hypertension 2000; 36 (2): 303–307.

    Article  CAS  Google Scholar 

  16. Pockley AG, de Faire U, Kiessling R, Lemne C, Thulin T, Frostegard J . Circulating heat shock protein and heat shock protein antibody levels in established hypertension. J Hypertens 2002; 20 (9): 1815–1820.

    Article  CAS  Google Scholar 

  17. Pockley AG, Georgiades A, Thulin T, de Faire U, Frostegard J . Serum heat shock protein 70 levels predict the development of atherosclerosis in subjects with established hypertension. Hypertension 2003; 42 (3): 235–238.

    Article  CAS  Google Scholar 

  18. Zhu J, Quyyumi AA, Wu H, Csako G, Rott D, Zalles-Ganley A et al. Increased serum levels of heat shock protein 70 are associated with low risk of coronary artery disease. Arterioscler Thromb Vasc Biol 2003; 23 (6): 1055–1059.

    Article  CAS  Google Scholar 

  19. Redman CW, Sargent IL . Latest advances in understanding preeclampsia. Science 2005; 308 (5728): 1592–1594.

    Article  CAS  Google Scholar 

  20. Redman CW, Sacks GP, Sargent IL . Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 1999; 180 (2, Part 1): 499–506.

    Article  CAS  Google Scholar 

  21. Redman CW, Sargent IL . The pathogenesis of pre-eclampsia. Gynecol Obstet Fertil 2001; 29 (7–8): 518–522.

    Article  CAS  Google Scholar 

  22. Xu Q, Wick G . The role of heat shock proteins in protection and pathophysiology of the arterial wall. Mol Med Today 1996; 2 (9): 372–379.

    Article  CAS  Google Scholar 

  23. Jirecek S, Hohlagschwandtner M, Tempfer C, Knofler M, Husslein P, Zeisler H . Serum levels of heat shock protein 70 in patients with preeclampsia: a pilot-study. Wien Klin Wochenschr 2002; 114 (15–16): 730–732.

    CAS  PubMed  Google Scholar 

  24. Fukushima A, Kawahara H, Isurugi C, Syoji T, Oyama R, Sugiyama T et al. Changes in serum levels of heat shock protein 70 in preterm delivery and pre-eclampsia. J Obstet Gynaecol Res 2005; 31 (1): 72–77.

    Article  CAS  Google Scholar 

  25. Livingston JC, Ahokas R, Haddad B, Sibai BM, Awaads R . Heat shock protein 70 is not increased in women with severe preeclampsia. Hypertens Pregnancy 2002; 21 (2): 123–126.

    Article  CAS  Google Scholar 

  26. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000; 183 (1): S1–S22.

  27. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Obstet Gynecol 2002; 99 (1): 159–167.

  28. Hung TH, Skepper JN, Burton GJ . In vitro ischemia–reperfusion injury in term human placenta as a model for oxidative stress in pathological pregnancies. Am J Pathol 2001; 159 (3): 1031–1043.

    Article  CAS  Google Scholar 

  29. Hnat MD, Meadows JW, Brockman DE, Pitzer B, Lyall F, Myatt L . Heat shock protein-70 and 4-hydroxy-2-nonenal adducts in human placental villous tissue of normotensive, preeclamptic and intrauterine growth restricted pregnancies. Am J Obstet Gynecol 2005; 193 (3, Part 1): 836–840.

    Article  CAS  Google Scholar 

  30. Hightower LE . Heat shock, stress proteins, chaperones, and proteotoxicity. Cell 1991; 66 (2): 191–197.

    Article  CAS  Google Scholar 

  31. Johnson AD, Berberian PA, Bond MG . Effect of heat shock proteins on survival of isolated aortic cells from normal and atherosclerotic cynomolgus macaques. Atherosclerosis 1990; 84 (2-3): 111–119.

    Article  CAS  Google Scholar 

  32. Johnson AD, Tytell M . Exogenous HSP70 becomes cell associated, but not internalized, by stressed arterial smooth muscle cells. In Vitro Cell Dev Biol Anim 1993; 29A (10): 807–812.

    Article  CAS  Google Scholar 

  33. Mosser DD, Caron AW, Bourget L, Meriin AB, Sherman MY, Morimoto RI et al. The chaperone function of hsp70 is required for protection against stress-induced apoptosis. Mol Cell Biol 2000; 20 (19): 7146–7159.

    Article  CAS  Google Scholar 

  34. Pockley AG . Heat shock proteins as regulators of the immune response. Lancet 2003; 362 (9382): 469–476.

    Article  CAS  Google Scholar 

  35. Asea A, Kraeft SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW et al. HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 2000; 6 (4): 435–442.

    Article  CAS  Google Scholar 

  36. Asea A, Rehli M, Kabingu E, Boch JA, Bare O, Auron PE et al. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem 2002; 277 (17): 15028–15034.

    Article  CAS  Google Scholar 

  37. Basu S, Binder RJ, Ramalingam T, Srivastava PK . CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 2001; 14 (3): 303–313.

    Article  CAS  Google Scholar 

  38. Prohaszka Z, Singh M, Nagy K, Kiss E, Lakos G, Duba J et al. Heat shock protein 70 is a potent activator of the human complement system. Cell Stress Chaperones 2002; 7 (1): 17–22.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by research grants from the Hungarian Scientific Research Fund (T 046837 and T 049531). The skilful technical assistance of Szigeti Antalné and the suggestions of Katalin Udvarnoki are acknowledged with many thanks.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Kútvölgyi Clinical Center, Semmelweis University, Budapest, Hungary

    A Molvarec & J Szalay

  2. 3rd Department of Internal Medicine, Semmelweis University and Research Group on Metabolism and Atherosclerosis, Hungarian Academy of Sciences, Budapest, Hungary

    Z Prohászka, G Füst & I Karádi

  3. 1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary

    B Nagy & J Rigó Jr

Authors
  1. A Molvarec
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Z Prohászka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Szalay
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G Füst
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. I Karádi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J Rigó Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A Molvarec.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Molvarec, A., Prohászka, Z., Nagy, B. et al. Association of elevated serum heat-shock protein 70 concentration with transient hypertension of pregnancy, preeclampsia and superimposed preeclampsia: a case–control study. J Hum Hypertens 20, 780–786 (2006). https://doi.org/10.1038/sj.jhh.1002060

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jhh.1002060

Keywords

This article is cited by

Search

Advanced search

Quick links