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Alteration of heat shock protein 20 expression in preeclamptic patients and its effect in vascular and coagulation function |
Fanfan Li1, Mengzhou He1, Meitao Yang1, Yao Fan1, Yun Chen2, Xi Xia2, Yin Xie1, Dongrui Deng1() |
1. Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 2. Ultrosonic Department, Peking University Shenzhen Hospital, Shenzhen 518035, China |
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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.
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Keywords
preeclampsia
heat shock protein 20
vascular relaxation
coagulation-fibrinolytic system
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Corresponding Author(s):
Dongrui Deng
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Just Accepted Date: 12 December 2017
Online First Date: 08 March 2018
Issue Date: 29 September 2018
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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
pmid: 24150027
|
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
https://doi.org/10.2215/CJN.12081115
pmid: 27094609
|
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
pmid: 26441469
|
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
https://doi.org/10.1161/CIRCULATIONAHA.109.853127
pmid: 21690502
|
5 |
Mol BW, Roberts CT, Thangaratinam S, Magee LA, de Groot CJ, Hofmeyr GJ. Pre-eclampsia. Lancet 2016; 387(10022): 999–1011
https://doi.org/10.1016/S0140-6736(15)00070-7
pmid: 26342729
|
6 |
Roberts JM, Lain KY. Recent insights into the pathogenesis of pre-eclampsia. Placenta 2002; 23(5): 359–372
https://doi.org/10.1053/plac.2002.0819
pmid: 12061851
|
7 |
Gathiram P, Moodley J. Pre-eclampsia: its pathogenesis and pathophysiolgy. Cardiovasc J Afr 2016; 27(2): 71–78
https://doi.org/10.5830/CVJA-2016-009
pmid: 27213853
|
8 |
Chaiworapongsa T, Chaemsaithong P, Yeo L, Romero R. Pre-eclampsia part 1: current understanding of its pathophysiology. Nat Rev Nephrol 2014; 10(8): 466–480
https://doi.org/10.1038/nrneph.2014.102
pmid: 25003615
|
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
https://doi.org/10.1002/jcb.24966
pmid: 25187324
|
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
https://doi.org/10.1007/s12013-012-9371-0
pmid: 22689214
|
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
https://doi.org/10.1016/j.ajog.2005.01.059
pmid: 16150283
|
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
https://doi.org/10.1007/s12192-009-0146-5
pmid: 19821156
|
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
https://doi.org/10.1016/S0024-3205(02)02144-6
pmid: 12417245
|
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
https://doi.org/10.1007/s12192-009-0127-8
pmid: 19568960
|
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 shock-related protein HSP20 leads to relaxation of vascular smooth muscle. FASEB J 2003; 17(10): 1358–1360
pmid: 12738803
|
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
https://doi.org/10.1016/j.jss.2004.01.001
pmid: 15093712
|
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
https://doi.org/10.1016/S0024-3205(02)02144-6
pmid: 12417245
|
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
https://doi.org/10.1016/S0014-5793(98)00626-7
pmid: 9662442
|
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
pmid: 10658928
|
20 |
Fan GC, Chu G, Kranias EG. Hsp20 and its cardioprotection. Trends Cardiovasc Med 2005; 15(4): 138–141
https://doi.org/10.1016/j.tcm.2005.05.004
pmid: 16099377
|
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-κB activation. J Mol Cell Cardiol 2009; 47(3): 382–390
https://doi.org/10.1016/j.yjmcc.2009.05.016
pmid: 19501592
|
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
https://doi.org/10.1371/journal.pone.0057451
pmid: 23437391
|
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
pmid: 10444513
|
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
https://doi.org/10.1093/molehr/gat045
pmid: 23775458
|
25 |
Edwards HV, Cameron RT, Baillie GS. The emerging role of HSP20 as a multifunctional protective agent. Cell Signal 2011; 23(9): 1447–1454
https://doi.org/10.1016/j.cellsig.2011.05.009
pmid: 21616144
|
26 |
Mymrikov EV, Seit-Nebi AS, Gusev NB. Large potentials of small heat shock proteins. Physiol Rev 2011; 91(4): 1123–1159
https://doi.org/10.1152/physrev.00023.2010
pmid: 22013208
|
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
https://doi.org/10.1097/MBC.0b013e3282f30d4c
pmid: 18277141
|
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
https://doi.org/10.137/journal.pone.0114488
pmid: 25464515
|
29 |
Townsley DM. Hematologic complications of pregnancy. Semin Hematol 2013; 50(3): 222–231
https://doi.org/10.1053/j.seminhematol.2013.06.004
pmid: 23953339
|
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
https://doi.org/10.1042/BST20140310
pmid: 26551715
|
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