Circulating heat shock protein 70 (HSPA1A) in normal and pathological pregnancies

Abstract

Heat shock proteins (Hsps) are ubiquitous and phylogenetically conserved molecules. They are usually considered to be intracellular proteins with molecular chaperone and cytoprotective functions. However, Hsp70 (HSPA1A) is present in the peripheral circulation of healthy nonpregnant and pregnant individuals. In normal pregnancy, circulating Hsp70 levels are decreased, and show a positive correlation with gestational age and an inverse correlation with maternal age. The capacity of extracellular Hsp70 to elicit innate and adaptive proinflammatory (Th1-type) immune responses might be harmful in pregnancy and may lead to the maternal immune rejection of the fetus. Decreased circulating Hsp70 level, consequently, may promote the maintenance of immunological tolerance to the fetus. Indeed, elevated circulating Hsp70 concentrations are associated with an increased risk of several pregnancy complications. Elevated Hsp70 levels in healthy pregnant women at term might also have an effect on the onset of labor. In preeclampsia, serum Hsp70 levels are increased, and reflect systemic inflammation, oxidative stress and hepatocellular injury. Furthermore, serum Hsp70 levels are significantly higher in patients with the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome) than in severely preeclamptic patients without HELLP syndrome. In HELLP syndrome, elevated serum Hsp70 level indicates tissue damage (hemolysis and hepatocellular injury) and disease severity. Increased circulating Hsp70 level may not only be a marker of these conditions, but might also play a role in their pathogenesis. Extracellular Hsp70 derived from stressed and damaged, necrotic cells can elicit a proinflammatory (Th1) immune response, which might be involved in the development of the maternal systemic inflammatory response and resultant endothelial damage in preeclampsia and HELLP syndrome. Circulating Hsp70 level is also elevated in preterm delivery high-risk patients, particularly in treatment-resistant cases, and may be a useful marker for evaluating the curative effects of treatment for preterm delivery. In addition, increased circulating Hsp70 levels observed in asthmatic pregnant patients might play a connecting role in the pathomechanism of asthmatic inflammation and obstetrical/perinatal complications. Nevertheless, a prospective study should be undertaken to determine whether elevated serum Hsp70 level precedes the development of any pregnancy complication, and thus can help to predict adverse maternal or perinatal pregnancy outcome. Moreover, the role of circulating Hsp70 in normal and pathological pregnancies is not fully known, and further studies are warranted to address this important issue.

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).…”

Serum level of soluble Hsp70 is associated with vascular calcification

“…Soluble Hsp70 showed no apparent endogenous circadian rhythm in a rested state (Fortes and Whitham 2009). Elevated serum Hsp70 level was measured in pathologic pregnancies (Molvarec et al 2009) such as preeclampsia and hemolytic anemia elevated liver enzymes low platelet count syndrome. Increased serum levels of Hsp70 levels were reported in patients with peripheral and renal vascular disease (Wright et al 2000) and after acute myocardial infarction (Dybdahl et al 2005;Satoh et al 2006), whereas circulating Hsp70 levels were positively related to markers of tissue damage including creatine kinase MB and cardiac troponin T. In chronic heart failure (CHF) patients increased serum Hsp70 levels were found compared to healthy controls (Genth-Zotz et al 2004).…”

Persistently elevated extracellular HSP70 (HSPA1A) level as an independent prognostic marker in post-cardiac-arrest patients

“…Elevated HSP70 was demonstrated in the HELLP syndrome, and HSP70 levels were associated with an increased risk of several pregnancy Table 2 a Spearman's rank-order correlation coefficients (r) with p values are presented complications (Molvarec et al 2010). Furthermore, increased HSP70 levels were found in patients with advanced, chronic heart failure, and were correlated with the markers of heart function (Gombos et al 2008).…”