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HSP70 Is Associated with Endothelial Activation in Placental Vascular Diseases
Molecular Medicine volume 14, pages 561–566 (2008)
Abstract
Endothelial cell injury and activation in the placenta are features of placental vascular disease (PVD). While advances in PVD have been made, the pathogenesis of this disease is still unknown. The objective of this study was to pursue potential risk factors and signal transcription pathways involved in PVD pathogenesis. Gene expression in subjects with PVD and with normal pregnancies was compared using a two-channel microarray technique. Higher expression of HSPA6 and HSPA1A was exhibited in PVD subjects. HSPA6 and HSPA1A both encode HSP70, and, therefore, we localized HSP70 expression in placental tissue. Using quantitative polymerase chain reaction (PCR) and Western blot, we observed a significant upregulation of HSP70 in both mRNA and protein levels in placental tissue and microvascular endothelial cells of PVD subjects when compared with normal pregnancies (P < 0.05). HSP70 mRNA and protein expression also correlated negatively with infant birth weight (P < 0.05). HSP70 was expressed mainly in endothelial cells and smooth muscle cells in the placental microvessels. We therefore conclude that HSP70 may mediate endothelial activation and play a role in pathogenesis of PVD.
References
Wang X, Athayde N, Trudinger B. (2003) A proinflammatory cytokine response is present in the fetal placental vasculature in placental insufficiency. Am. J. Obstet. Gynecol. 189:1445–51.
Meekins JW, Pijnenborg R, Hanssens M, Mc-Fadyen IR, van Asshe A. (1994) A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. Br. J. Obstet. Gynaecol. 101:669–74.
Aquilina J, Harrington K. (1996) Pregnancy hypertension and uterine artery Doppler ultrasound. Curr. Opin. Obstet. Gynecol. 8:435–40.
Trudinger B, Wang J, Athayde N, Beutler L, Wang X. (2002) Association of umbilical placental vascular disease with fetal acute inflammatory cytokine responses. J. Soc. Gynecol. Investig. 9:152–7.
Lindquist S, Craig EA. (1988) The heat-shock proteins. Annu. Rev. Genet. 22:631–77.
Fink AL. (1999) Chaperone-mediated protein folding. Physiol. Rev. 79:425–49.
Jaattela M. (1999) Heat shock proteins as cellular lifeguards. Ann. Med. 31:261–71.
Shah M, Stanek J, Handwerger S. (1998) Differential localization of heat shock proteins 90, 70, 60 and 27 in human decidua and placenta during pregnancy. Histochem. J. 30:509–18.
Divers MJ, Bulmer JN, Miller D, Lilford RJ. (1995) Placental heat shock proteins: no immunohistochemical evidence for a differential stress response in preterm labour. Gynecol. Obstet. Invest. 40:236–43.
Jirecek S, et al. (2002) Serum levels of heat shock protein 70 in patients with preeclampsia: a pilotstudy. Wien Klin. Wochenschr. 114:730–2.
Wright BH, Corton J, El-Nahas AM, Wood RFM, Pockley AG. (2000) Elevated levels of circulating heat shock protein 70 (Hsp70) in peripheral and renal vascular disease. Heart Vessels 15:18–22.
Malyshev IY, Manukhina EB, Mikoyan VD, Kubrina LN, Vanin AF. (1995) Nitric oxide is involved in heat-induced HSP70 accumulation. FEBS Lett. 370:159–62.
Kiang JH and Tsokos GC. (1998) Heat shock protein 70 kDa: molecular biology, biochemistry, and physiology. Pharmacol. Ther. 80:183–201.
Asea A. (2005) Stress proteins and initiation of immune response: chaperokine activity of hsp72. Exerc. Immunol. Rev. 11:34–45.
Asea A, et al. (2002) Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J. Biol. Chem. 277:15028–34.
Asea A, et al. (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat. Med. 6:435–42.
Wang X, Athayde N, Trudinger B. (2005) Placental vascular disease and toll-like receptor 4 gene expression. Am. J. Obstet. Gynecol. 192:961–6.
Wang X, Athayde N, Trudinger B. (2004) Microvascular endothelial cell activation is present in the umbilical placental microcirculation in fetal placental vascular disease. Am. J. Obstet. Gynecol. 190:596–601.
Patterson TA, et al. (2006) Performance comparison of one-color and two-color platforms within the MicroArray Quality Control (MAQC) project. Nat. Biotechnol. 24:1140–50.
Bretelle F, et al. (2004) New insight in physiopathology of preeclampsia and intra-uterine growth retardation: role of inflammation. Gynecol. Obstet. Fertil. 32:482–9.
Pockley AG. (2002) Heat shock proteins, inflammation, and cardiovascular disease. Circulation 105:1012–7.
Alain Tedgui, Ziad Mallat. (2006) Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol. Rev. 86:515–81.
Bobryshev YV, Lord RS. (2002) Expression of heat shock protein-70 by dendritic cells in the arterial intima and its potential significance in atherogenesis. J. Vasc. Surg. 35:368–75.
Welch WJ. (1992) Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease. Physiol. Rev. 72:1063–81.
Kiang JG, Tsokos GC. (1998) Heat shock protein 70 kDa: molecular biology, biochemistry, and physiology. Pharmacol. Ther. 80:183–201.
Acknowledgments
This work was supported by National Natural Science Foundation of China (30471825). We thank the staff in the Department of Obstetrics and Gynecology of Shandong Provincial Hospital for helping with patients’ identification and tissue collection.
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Liu, Y., Li, N., You, L. et al. HSP70 Is Associated with Endothelial Activation in Placental Vascular Diseases. Mol Med 14, 561–566 (2008). https://doi.org/10.2119/2008-00009.Liu
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DOI: https://doi.org/10.2119/2008-00009.Liu