High levels of heat shock protein 70 are associated with pro-inflammatory cytokines and may differentiate early- from late-onset preeclampsia

Peraçoli, José Carlos; Bannwart-Castro, Camila F.; Romão, Mariana; Weel, Ingrid C.; Ribeiro, Vanessa Rocha; Borges, Vera Therezinha Medeiros; Rudge, Marilza Vieira Cunha; Witkin, Steven S.; Peraçoli, Maria Terezinha Serrão

doi:10.1016/j.jri.2013.08.003

Cited by 65 publications

(61 citation statements)

References 41 publications

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“…10,15,18 Increased levels of heat-shock protein 70 (Hsp70) associated with higher levels of TNF-a, IL-1b, IL-12, and soluble TNF receptor-I (sTN-FRI) have been described in serum from women with early-onset PE compared with those with late-onset PE. 41 The higher levels of Hsp70 may originate from the ischaemic and oxidatively stressed pre-eclamptic placenta 42 and are released into the circulation in women with PE by increased shedding of syncytiotrophoblast membrane microparticles, leading to peripheral blood cell activation. These results support a pro-inflammatory role of circulating Hsp70 in PE.…”

Section: Discussionmentioning

confidence: 99%

Monocytes from Pregnant Women with Pre-Eclampsia are Polarized to a M1 Phenotype

Medeiros

Peraçoli

Bannwart-Castro

et al. 2014

Am J Reprod Immunol

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Section: Discussionmentioning

confidence: 99%

Monocytes from Pregnant Women with Pre-Eclampsia are Polarized to a M1 Phenotype

Medeiros

Peraçoli

Bannwart-Castro

et al. 2014

Am J Reprod Immunol

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“…For example, in the early phase of stroke (within the first few hours), there is a many-fold increase in TNFα, IL-1, and IL-6 levels 26. This pro-inflammatory phase is followed by an increase in anti-inflammatory cytokines (eg, IL-10 and IL-1 receptor antagonist) that may reduce the intensity of the inflammatory response 27.…”

Section: Discussionmentioning

confidence: 99%

Neurotherapeutic activity of the recombinant heat shock protein Hsp70 in a model of focal cerebral ischemia in rats

Shevtsov¹,

Nikolaev²,

Yakovleva³

et al. 2014

DDDT

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Recombinant 70 kDa heat shock protein (Hsp70) is an antiapoptotic protein that has a cell protective activity in stress stimuli and thus could be a useful therapeutic agent in the management of patients with acute ischemic stroke. The neuroprotective and neurotherapeutic activity of recombinant Hsp70 was explored in a model of experimental stroke in rats. Ischemia was produced by the occlusion of the middle cerebral artery for 45 minutes. To assess its neuroprotective capacity, Hsp70, at various concentrations, was intravenously injected 20 minutes prior to ischemia. Forty-eight hours after ischemia, rats were sacrificed and brain tissue sections were stained with 2% triphenyl tetrazolium chloride. Preliminary treatment with Hsp70 significantly reduced the ischemic zone (optimal response at 2.5 mg/kg). To assess Hsp70’s neurotherapeutic activity, we intravenously administered Hsp70 via the tail vein 2 hours after reperfusion (2 hours and 45 minutes after ischemia). Rats were then kept alive for 72 hours. The ischemic region was analyzed using a high-field 11 T MRI scanner. Administration of the Hsp70 decreased the infarction zone in a dose-dependent manner with an optimal (threefold) therapeutic response at 5 mg/kg. Long-term treatment of the ischemic rats with Hsp70 formulated in alginate granules with retarded release of protein further reduced the infarct volume in the brain as well as apoptotic area (annexin V staining). Due to its high neurotherapeutic potential, prolonged delivery of Hsp70 could be useful in the management of acute ischemic stroke.

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“…Elevated circulating Hsp70 concentrations reflecting systemic inflammation, oxidative stress and hepatocellular injury were found to be associated with an increased risk of several pregnancy-related complications including transient hypertension of pregnancy, PE, haemolysis, elevated liver enzymes, low platelet syndrome and pre-term delivery121314151617. Elevation of circulating Hsp70 levels was also observed in pregnant asthmatic women compared to healthy pregnant women18.…”

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confidence: 99%

“…Since most investigators studied Hsp expression at protein level in placental tissues19202122 and maternal circulation (serum or plasma samples)12131415161718, we focused on the examination of Hsp expression at mRNA level. Among differentially expressed proteins, previous studies identified Hsp27 and Hsp70 to be upregulated in placental tissues derived from patients with PE19202122.…”

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confidence: 99%

Circulating heat shock protein mRNA profile in gestational hypertension, pre-eclampsia & foetal growth restriction

Hromadníková¹,

Dvořáková²,

Kotlabova³

et al. 2016

Indian J Med Res

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Background & objectives:Heat shock proteins (Hsp) are ubiquitously distributed phylogenetically conserved molecules that regulate cellular homeostasis and maintain the integrity and function of cellular proteins. Increased levels of Hsp in maternal circulation have been shown to be associated with increased risk of pregnancy related complications. The objective of this study was to explore extracellular Hsp mRNA levels in maternal circulation and quantified Hsp27, Hsp60, Hsp70, Hsp90 and Hsp70 binding protein 1 (HspBP1) mRNAs in maternal plasma samples using real-time reverse-transcriptase polymerase chain reaction.Methods:Pregnancies with gestational hypertension (GH) (n = 33), pre-eclampsia (PE) with or without foetal growth restriction (FGR) (n = 78) and FGR (n = 25) were involved in the study. Hsp gene expression was analysed in relation to the severity of the disease with respect to the degree of clinical signs, requirements for the delivery and Doppler ultrasound parameters.Results:Upregulation of Hsp70 was observed in patients with mild and severe PE (P = 0.004 and P = 0.005, respectively) and in pregnancies complicated with PE delivering before and after 34 wk of gestation regardless of the degree of clinical signs (P = 0.015 and P = 0.009, respectively). No difference in the expression of other Hsp genes among the studied groups was observed. No association between Hsp gene expression and Doppler ultrasonography parameters was found.Interpretation & conclusions:These data support that maternal circulation can reflect both maternal and foetal pathologic conditions. Hsp70 represents the sole plasmatic marker, and increased Hsp70 mRNA levels reflect maternal and placental stress response to pregnancy-related complications such as GH and PE, irrespective of the severity of the disease.

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High levels of heat shock protein 70 are associated with pro-inflammatory cytokines and may differentiate early- from late-onset preeclampsia

Cited by 65 publications

References 41 publications

Monocytes from Pregnant Women with Pre-Eclampsia are Polarized to a M1 Phenotype

Monocytes from Pregnant Women with Pre-Eclampsia are Polarized to a M1 Phenotype

Neurotherapeutic activity of the recombinant heat shock protein Hsp70 in a model of focal cerebral ischemia in rats

Circulating heat shock protein mRNA profile in gestational hypertension, pre-eclampsia & foetal growth restriction

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