Increased serum heat-shock protein 70 levels reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia

Abstract

It has been previously reported that serum levels of 70-kDa heat-shock protein (Hsp70) are elevated in preeclampsia. The aim of the present study was to examine whether increased serum Hsp70 levels are related to clinical characteristics and standard laboratory parameters of preeclamptic patients, as well as to markers of inflammation (C-reactive protein), endothelial activation (von Willebrand factor antigen) or endothelial injury (fibronectin), trophoblast debris (cell-free fetal DNA) and oxidative stress (malondialdehyde). Sixty-seven preeclamptic patients and 70 normotensive, healthy pregnant women were involved in this case-control study. Serum Hsp70 levels were measured with enzyme-linked immunosorbent assay (ELISA). Standard laboratory parameters (clinical chemistry) and C-reactive protein (CRP) levels were determined by an autoanalyzer using the manufacturer's kits. Plasma von Willebrand factor antigen (VWF:Ag) levels were quantified by ELISA, and plasma fibronectin concentration by nephelometry. The amount of cell-free fetal DNA in maternal plasma was determined by quantitative real-time polymerase chain reaction analysis of the sex-determining region Y gene. Plasma malondialdehyde levels were measured by the thiobarbituric acid-based colorimetric assay. Serum Hsp70 levels were increased in preeclampsia. Furthermore, serum levels of blood urea nitrogen, creatinine, bilirubin and CRP, serum alanine aminotransferase and lactate dehydrogenase (LDH) activities, as well as plasma levels of VWF:Ag, fibronectin, cell-free fetal DNA and malondialdehyde were also significantly higher in preeclamptic patients than in normotensive, healthy pregnant women. In preeclamptic patients, serum Hsp70 levels showed significant correlations with serum CRP levels (Spearman R = 0.32, p = 0.010), serum aspartate aminotransferase (R = 0.32, p = 0.008) and LDH activities (R = 0.50, p < 0.001), as well as with plasma malondialdehyde levels (R = 0.25, p = 0.043). However, there was no other relationship between serum Hsp70 levels and clinical characteristics (age, parity, body mass index, blood pressure, gestational age, fetal birth weight) and laboratory parameters of preeclamptic patients, including markers of endothelial activation or injury and trophoblast debris. In conclusion, increased serum Hsp70 levels seem to reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia. Nevertheless, further studies are required to determine whether circulating Hsp70 plays a causative role in the pathogenesis of the disease.

Maternal exposure to heatwave and preterm birth inBrisbane,Australia

“…42 Furthermore, studies also found a significant increase of serum heat-shock protein (HSP70) levels in women with preterm birth and pre-eclampsia, as human cells and tissues may produce HSP70 rapidly to recover structural and functional damage caused by the incorrect folding of proteins. [43][44][45][46] The associations in this study were robust to the definitions of heatwave, persisted after adjustment for confounding factors, followed a dose-response relationship with increasing temperature, and were consistent with other international studies. In addition, there are plausible biological mechanisms that can explain the association: all of these factors supported the interpretation that the relationship between short-term heatwave exposure and preterm birth is causal.…”

Increased heat shock protein 70 levels in induced sputum and plasma correlate with severity of asthma patients

“…When HSPs are released into the extracellular compartment, they are able to deliver a partial maturation signal to dendritic cells, which may play a crucial role in pathogenesis of asthma and activate the NF-kappaB pathway, and can also stimulate pro-inflammatory cytokines production in vitro (Asea et al 2000;Basu et al 2000). This suggests that HSP70 may modulate and exert immune and inflammatory responses and may be involved in the pathogenesis and/or be markers of some diseases like atherosclerosis, ischemia-reperfusion injury, preeclampsia, and HELLP syndrome (Bielecka-Dabrowa et al 2009;Molvarec et al 2007Molvarec et al , 2009Molvarec et al , 2010Walsh et al 2009). Meanwhile, it has been found that extracellular HSP70 level is increased in patients with sarcoidosis and chronic beryllium disease (Silva et al 2007) and COPD patients (Hacker et al 2009).…”

Decreased Serum Bilirubin Is Associated With Silent Cerebral Infarction

“…10 Serum bilirubin (a heme catabolic product) is among the most powerful endogenous antioxidative substances and is positively correlated with the total antioxidant capacity in Gilbert syndrome. 11 A lower prevalence of cardiovascular disease is found in Gilbert disease. 12 However, TB exerts a toxic effect in certain situations.…”

“…Alcohol consumption was categorized as never, light (≤ 6 drinks/week), moderate (7)(8)(9)(10)(11)(12)(13)(14) drinks/week), heavy (≥ 15 drinks/week). Blood pressure was determined using a mercury-gravity sphygmomanometer in a sitting position after a 15-min rest.…”