Skip to main content
Log in

Alteration of heat shock protein 20 expression in preeclamptic patients and its effect in vascular and coagulation function

  • Research Article
  • Published:
Frontiers of Medicine Aims and scope Submit manuscript

Abstract

Preeclampsia (PE) is a pregnancy-specific, multi-system disorder and the leading cause of maternal and perinatal morbidity and mortality in obstetrics worldwide. Excessive vasoconstriction and dysregulated coagulation function are closely associated with PE. Heat shock protein 20 (HSP20) is ubiquitously expressed under normal physiological conditions and has important roles in vascular dilatation and suppression of platelet aggregation. However, the role of HSP20 in the pathogenesis of PE remains unclear. In this study, we collected chorionic plate resistance arteries (CPAs) and serum from 118 healthy pregnant women and 80 women with PE and detected the levels of HSP20 and its phosphorylated form. Both HSP20 and phosphorylated HSP20 were downregulated in CPAs from women with PE. Comparison of the vasodilative ability of CPAs from the two groups showed impaired relaxation responses to acetyl choline in preeclamptic vessels. In addition to the reduced HSP20 in serum from women with PE, the platelet distribution width and mean platelet volume were also decreased, and the activated partial thromboplastin time and thromboplastin time were elevated.With regard to the vital roles of HSP20 in mediating vasorelaxation and coagulation function, the decreased HSP20 might contribute to the pathogenesis of PE.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Roberts JM, August PA, Bakris G, Barton JR, Bernstein IM, Druzin M, Gaiser RR, Granger JP, Jeyabalan A, Johnson DD, Karumanchi S, Lindheimer M, Owens MY, Saade GR, Sibai BM, Spong CY, Tsigas E, Joseph GF, O’Reilly N, Politzer A, Son S, Ngaiza K; American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013; 122(5): 1122–1131

    Article  Google Scholar 

  2. Phipps E, Prasanna D, Brima W, Jim B. Preeclampsia: updates in pathogenesis, definitions, and guidelines. Clin J Am Soc Nephrol 2016; 11(6): 1102–1113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. McLaughlin K, Drewlo S, Parker JD, Kingdom JC. Current theories on the prevention of severe preeclampsia with low-molecular weight heparin. Hypertension 2015; 66(6): 1098–1103

    Article  CAS  PubMed  Google Scholar 

  4. Powe CE, Levine RJ, Karumanchi SA. Preeclampsia, a disease of the maternal endothelium: the role of antiangiogenic factors and implications for later cardiovascular disease. Circulation 2011; 123 (24): 2856–2869

    Article  PubMed  Google Scholar 

  5. Mol BW, Roberts CT, Thangaratinam S, Magee LA, de Groot CJ, Hofmeyr GJ. Pre-eclampsia. Lancet 2016; 387(10022): 999–1011

    Article  PubMed  Google Scholar 

  6. Roberts JM, Lain KY. Recent insights into the pathogenesis of preeclampsia. Placenta 2002; 23(5): 359–372

    Article  CAS  PubMed  Google Scholar 

  7. Gathiram P, Moodley J. Pre-eclampsia: its pathogenesis and pathophysiolgy. Cardiovasc J Afr 2016; 27(2): 71–78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chaiworapongsa T, Chaemsaithong P, Yeo L, Romero R. Preeclampsia part 1: current understanding of its pathophysiology. Nat Rev Nephrol 2014; 10(8): 466–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ju YT, Kwag SJ, Park HJ, Jung EJ, Jeong CY, Jeong SH, Lee YJ, Choi SK, Kang KR, Hah YS, Hong SC. Decreased expression of heat shock protein 20 in colorectal cancer and its implication in tumorigenesis. J Cell Biochem 2015; 116(2): 277–286

    Article  CAS  PubMed  Google Scholar 

  10. Padmini E, Uthra V, Lavanya S. Effect of HSP70 and 90 in modulation of JNK, ERK expression in preeclamptic placental endothelial cell. Cell Biochem Biophys 2012; 64(3): 187–195

    Article  CAS  PubMed  Google Scholar 

  11. 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): 836–840

    Article  CAS  PubMed  Google Scholar 

  12. Molvarec A, Tamási L, Losonczy G, Madách K, Prohászka Z, Rigó J Jr. Circulating heat shock protein 70 (HSPA1A) in normal and pathological pregnancies. Cell Stress Chaperones 2010; 15(3): 237–247

    Article  CAS  PubMed  Google Scholar 

  13. Kozawa O, Matsuno H, Niwa M, Hatakeyama D, Oiso Y, Kato K, Uematsu T. HSP20, low-molecular-weight heat shock-related protein, acts extracellularly as a regulator of platelet functions: a novel defense mechanism. Life Sci 2002; 72(2): 113–124

    Article  CAS  PubMed  Google Scholar 

  14. Dreiza CM, Komalavilas P, Furnish EJ, Flynn CR, Sheller MR, Smoke CC, Lopes LB, Brophy CM. The small heat shock protein, HSPB6, in muscle function and disease. Cell Stress Chaperones 2010; 15(1): 1–11

    Article  CAS  PubMed  Google Scholar 

  15. Flynn CR, Komalavilas P, Tessier D, Thresher J, Niederkofler EE, Dreiza CM, Nelson RW, Panitch A, Joshi L, Brophy CM. Transduction of biologically active motifs of the small heat shockrelated protein HSP20 leads to relaxation of vascular smooth muscle. FASEB J 2003; 17(10): 1358–1360

    Article  CAS  PubMed  Google Scholar 

  16. Tessier DJ, Komalavilas P, McLemore E, Thresher J, Brophy CM. Sildenafil-induced vasorelaxation is associated with increases in the phosphorylation of the heat shock-related protein 20 (HSP20). J Surg Res 2004; 118(1): 21–25

    Article  CAS  PubMed  Google Scholar 

  17. Kozawa O, Matsuno H, Niwa M, Hatakeyama D, Oiso Y, Kato K, Uematsu T. HSP20, low-molecular-weight heat shock-related protein, acts extracellularly as a regulator of platelet functions: a novel defense mechanism. Life Sci 2002; 72(2): 113–124

    Article  CAS  PubMed  Google Scholar 

  18. Matsuno H, Kozawa O, Niwa M, Usui A, Ito H, Uematsu T, Kato K. A heat shock-related protein, p20, plays an inhibitory role in platelet activation. FEBS Lett 1998; 429(3): 327–329

    Article  CAS  PubMed  Google Scholar 

  19. Niwa M, Kozawa O, Matsuno H, Kato K, Uematsu T. Small molecular weight heat shock-related protein, HSP20, exhibits an anti-platelet activity by inhibiting receptor-mediated calcium influx. Life Sci 2000; 66(1): PL7–PL12

    CAS  PubMed  Google Scholar 

  20. Fan GC, Chu G, Kranias EG. Hsp20 and its cardioprotection. Trends Cardiovasc Med 2005; 15(4): 138–141

    Article  CAS  PubMed  Google Scholar 

  21. Wang X, Zingarelli B, O’Connor M, Zhang P, Adeyemo A, Kranias EG, Wang Y, Fan GC. Overexpression of Hsp20 prevents endotoxin-induced myocardial dysfunction and apoptosis via inhibition of NF-kB activation. J Mol Cell Cardiol 2009; 47(3): 382–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Brereton MF, Wareing M, Jones RL, Greenwood SL. Characterisation of K+ channels in human fetoplacental vascular smooth muscle cells. PLoS One 2013; 8(2): e57451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Amarnani S, Sangrat B, Chaudhuri G. Effects of selected endothelium-dependent vasodilators on fetoplacental vasculature: physiological implications. Am J Physiol 1999; 277(2 Pt 2): H842–H847

    CAS  PubMed  Google Scholar 

  24. Dordea AC, Sweeney M, Taggart J, Lartey J,Wessel H, Robson SC, Taggart MJ. Differential vasodilation of human placental and myometrial arteries related to myofilament Ca2+-desensitization and the expression of Hsp20 but not MYPT1. Mol Hum Reprod 2013; 19(11): 727–736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Edwards HV, Cameron RT, Baillie GS. The emerging role of HSP20 as a multifunctional protective agent. Cell Signal 2011; 23(9): 1447–1454

    Article  CAS  PubMed  Google Scholar 

  26. Mymrikov EV, Seit-Nebi AS, Gusev NB. Large potentials of small heat shock proteins. Physiol Rev 2011; 91(4): 1123–1159

    Article  CAS  PubMed  Google Scholar 

  27. Desprez D, Zobairi F, Aucouturier JS, Leymarie F, Freyssinet JM, Grunebaum L, de Raucourt E. Evolution of circulating procoagulant microparticles during normal pregnancy. Blood Coagul Fibrinolysis 2008; 19(2): 179–181

    Article  PubMed  Google Scholar 

  28. Han L, Liu XJ, Li HM, Zou JQ, Yang ZL, Han J, Huang W, Yu LL, Zheng YR, Li L. Blood coagulation parameters and platelet indices: changes in normal and preeclamptic pregnancies and predictive values for preeclampsia. PLoS One 2014; 9(12): e114488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Townsley DM. Hematologic complications of pregnancy. Semin Hematol 2013; 50(3): 222–231

    Article  PubMed  PubMed Central  Google Scholar 

  30. Egan K, Kevane B, Ní Áinle F. Elevated venous thromboembolism risk in preeclampsia: molecular mechanisms and clinical impact. Biochem Soc Trans 2015; 43(4): 696–701

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We acknowledge the funding support from the National Science and Technology Pillar Program of China during the Twelfth Five-Year Plan Period (No. 2014BAI 05B05), the National Natural Science Foundation of China (No. 81172464), the Fundamental Research Funds for the Central Universities (No. 2017KFYXJJ102), and Guangdong Natural Scientific Foundation (Nos. 2015A030313889 and 2014A030313797).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dongrui Deng.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, F., He, M., Yang, M. et al. Alteration of heat shock protein 20 expression in preeclamptic patients and its effect in vascular and coagulation function. Front. Med. 12, 542–549 (2018). https://doi.org/10.1007/s11684-017-0576-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-017-0576-x

Keywords

Navigation