Serum Heat Shock Protein 70 Levels Research Articles

What is in common between preeclampsia, HPS70 and medieval headwear? Part II. Serum HSP70 in superimposed preeclampsia: original study

The objective: to investigate serum heat shock protein 70 (HSP70) concentration in pregnant women with chronic hypertension and superimposed preeclampsia. To assess the prospects of using HSP70 as a superimposed preeclampsia predictor.Materials and methods. The original prospective cohort single-center observational study included 105 pregnant women with chronic hypertension and 34 healthy pregnant women as a control group. Serum HSP70 was measured via enzyme-linked immunosorbent assay. The first measurement point of serum HSP70 was at 28 weeks of gestation, the second measurement point was at 36 weeks in case of absence of preeclampsia or at 29-35 weeks in case of preeclampsia. If signs of preeclampsia appeared later than 36 weeks, additional HSP70 measurement was not performed. Statistical analysis was conducted using EZR 1.55 software.Results. In the study group (105 pregnant women with chronic hypertension), after delivery 30 patients had signs of superimposed preeclampsia (superimposed preeclampsia subgroup) and 75 persons had no signs of superimposed preeclampsia (chronic hypertension subgroup). In the control group (34 healthy pregnant women) 3 patients after delivery had preeclampsia signs (preeclampsia subgroup) and another 31 had no signs of preeclampsia (healthy subgroup).Serum HSP70 levels, obtained at the first measurement point (28 weeks) was statistically significantly different between three subgroups: patients with chronic hypertension vs. patients with superimposed preeclampsia (p<0.01), healthy pregnant women vs. chronic hypertension women (p<0.0001), healthy persons vs. superimposed preeclampsia persons (p<0.0001).Serum HSP70 concentrations at the second measurement point (36 weeks, or 29-35 weeks in case of preeclampsia) also had a statistically significant difference for each pair of subgroups (p<0.001). Given the small number of persons in the preeclampsia subgroup (3 women), it was not included in the calculations.No statistically significant difference between serum HSP70 levels in the first and second measurement points was found in healthy pregnant women subgroup. In the subgroup of pregnant women with chronic hypertension without superimposed preeclampsia complications, a statistically significant increased serum HSP70 concentration was found at 36 weeks compared to 28 weeks (p<0.0001). Even bigger growth of HSP70 levels compared to 28 weeks occurred in case of joining preeclampsia to chronic hypertension (p<0.0001).Conclusions. The data suggest an increased concentration of HSP70 in pregnant women with superimposed preeclampsia compared to pregnant women with chronic hypertension of the corresponding term. Thus, it is possible to assume that HSP70 plays a role in superimposed preeclampsia pathogenesis.The increased serum HSP70 levels in pregnant women with chronic hypertension, compared to healthy pregnant women of the corresponding gestational age was determined. Therefore, it can be argued that HSP70 has an influence on the course of chronic hypertension during pregnancy.No statistically significant dependance of serum HSP70 level in healthy pregnant women on gestational age was found. The increase in the level of HSP70 in pregnant women with chronic hypertension with increasing gestational age is most likely due to the progression of hypertensive disorders and/or related conditions. The highest HSP70 increase was observed in pregnant women with chronic hypertension with the addition of preeclampsia.The use of HSP70 as the only predictor of superimposed preeclampsia is not effective, given its non-specificity, but the use of this indicator in combination with other markers is promising and requires further study.

Serum oxidative stress factors predict myocardial ischemia reperfusion injury after percutaneous coronary intervention in patients with acute myocardial infarction and type 2 diabetes mellitus.

Serum oxidative stress factors may be considered to be essential parameters for indicating cell oxidative damage. We designed this study to investigate the clinical diagnostic value of serum oxidative stress factors (superoxide dismutase (SOD), malondialdehyde (MDA), and myeloperoxidase (MPO)) combined with ischemia-modified albumin (IMA) and heat shock protein 70 (HSP70) for myocardial ischemia-reperfusion injury (MIRI) after percutaneous coronary intervention (PCI) in elderly patients with acute myocardial infarction (AMI) and type 2 diabetes mellitus (T2DM). From November 2020 to August 2021, 94 patients with AMI + T2DM and 86 patients with AMI were enrolled in the study; they were sub-grouped into the MIRI and non-MIRI groups following the occurrence of MIRI within 48 h after PCI. SOD, MDA, MPO, IMA, and HSP70 levels were determined. The clinical values of the combined serum oxidative stress factors, IMA, and HSP70 levels to predict MIRI events were analyzed. There was a higher probability of MIRI events in the AMI + T2DM group than the AMI group (p < 0.05). The ROC curve for the combined prediction of SOD, MDA, MPO, IMA, and HSP70 for the occurrence of MIRI events was higher in both the AMI and the AMI + T2DM groups than for predictive factors alone (all p < 0.05). Combined prediction of SOD, MDA, MPO, IMA, and HSP70 has the highest diagnostic value for predicting MIRI events after PCI in AMI patients, especially in patients with AMI combined with T2DM.

Hyperbaric Oxygen Therapy Promotes Hearing Gain with Increases in Serum IGF-1 and HSP70 in Patients with Idiopathic Sudden Sensorineural Hearing Loss.

Hyperbaric oxygen therapy (HBOT) has been recommended for the initial and salvage treatment of patients with idiopathic sudden sensorineural hearing loss (ISSHL), but its underlying mechanisms remain unclear. In this study, we investigated whether HBOT alters serum levels of insulin-like growth factor 1 (IGF-1) and heat shock protein 70 (HSP70) in patients with ISSHL. Then, we identified the relationship between hearing recovery and changes in serum IGF-1 and HSP70 levels. Moderately severe to profound unilateral ISSHL patients (n = 70) and healthy control participants (n = 30) were enrolled. The ISSHL patients were randomly assigned to receive medical therapy alone (MT group, n = 35) or both HBOT and medical therapy (HBOT + MT group, n = 35). Audiometric testing was performed before and after treatment. Serum IGF-1 and HSP70 levels were assessed by ELISA in ISSHL patients pre-and posttreatment and healthy controls. Before treatment, compared with the healthy controls, serum IGF-1 and HSP70 were lower in ISSHL patients. After treatment, serum IGF-1 and HSP70 increased in both the HBOT + MT and MT groups, although they were significantly higher in the HBOT + MT group (p < 0.01). In the HBOT + MT group, these increases were associated with hearing gains. In addition, IGF-1 was strongly associated with HSP70 (r = 0.621, p = 0.001). No such association was found in the MT group (p = 0.757). Administering HBOT in addition to medical therapy can improve the hearing of patients with moderately severe to profound unilateral ISSHL. The improvement is related to the upregulation of IGF-1 and HSP70.

The abnormal level of HSP70 is related to Treg/Th17 imbalance in PCOS patients

BackgroundPolycystic ovary syndrome (PCOS) is a disease with chronic nonspecific low-grade inflammation. The imbalance of immune cells exists in PCOS. Several studies have found that heat shock protein 70 (HSP70) may be involved in the immunological pathogenesis of PCOS, but the relationship between HSP70 and Regulatory T cell (Treg)/T helper cell 17(Th17) ratio remains unclear. This study aims to explore the correlation between HSP70 and Treg/Th17 ratio and to provide evidence for the role of HSP70 in the immunological etiology of PCOS.ResultsThere was no significant difference in age and body mass index (BMI) between the two groups. The concentrations of basal estradiol (E2), basal follicle-stimulating hormone (FSH) did not show a significant difference between the two groups. The concentrations of basal luteinizing hormone (LH) (P < 0.01), testosterone (T) (P < 0.01), glucose (P < 0.001) and insulin (P < 0.001) in PCOS patients were significantly higher than those in the control group. The protein levels of HSP70 were significantly higher in serum in the PCOS group (P < 0.001). The percentage of Treg cells was significantly lower (P < 0.01), while the percentage of the Th17 cells of the PCOS group was significantly higher than that of the control group (P < 0.05). The ratio of Treg/Th17 in the PCOS group was significantly lower (P < 0.001). The concentrations of Interleukin (IL)-6, IL-17, and IL-23 were significantly higher, while the levels of IL-10 and Transforming growth factor-β (TGF-β) were significantly lower in the PCOS group (P < 0.001). Spearman rank correlation analysis showed a strong negative correlation of serum HSP70 levels with Treg/Th17 ratio, IL-10, and TGF-β levels. In contrast, HSP70 levels were significantly positively correlated with IL-6, IL-17, IL-23, LH, insulin, and glucose levels.ConclusionThe abnormal level of HSP70 is correlated with Treg/Th17 imbalance and corresponding cytokines, which indicates that HSP70 may play an important role in PCOS immunologic pathogenesis.

Chrysin ameliorates STZ-induced diabetes in rats: possible impact of modulation of TLR4/NF-κβ pathway.

Background and purpose:Growing evidence advocates that upregulation of toll-like receptor 4 (TLR4) has been suggested as a causative influence in the development and complications of diabetes mellitus. We aimed to study the antidiabetic activity of chrysin against streptozotocin (STZ)-induced diabetes via down-regulation of TLR4/nuclear factor (NF-κβ)/heat shock protein 70 (HSP70) pathway as well as modulation of clusters of differentiation 4 (CD4+) in rats.Experimental approach:Fifty rats were divided into five groups (n = 10). Group I, normal rats received a single intraperitoneal injection of buffer citrate; group II, STZ-induced diabetic rats; groups III-V, diabetic rats received glimepiride (0.5 mg/kg; p.o.) or chrysin (40 and 80 mg/kg; p.o.) respectively, for 10 days. Serum samples were extracted to determine nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH), insulin, CD4+, TLR4, and NF-κβ. Pancreatic tissue samples were extracted to determine glucose transporter 2 (GLUT2). Part of the pancreas was kept in formalin for pathological studies.Findings/Results:An elevation in blood glucose, NO, and MDA serum levels and a reduction of pancreatic GLUT2 content, insulin, and GSH serum levels were observed in diabetic rats. STZ injection, also, showed an increase in serum TLR4, NF-κβ, and HSP70 levels and a reduction in serum CD4+ levels with pancreatic cells necrosis. These biochemical and histological changes were reversed in glimepiride and chrysin groups.Conclusion and implications:The present study proved that chrysin has a potent anti-diabetic effect through the elevation of insulin and GLUT2 levels, the reduction of oxidative stress, and the inflammatory pathways TLR4/NF-κβ/HSP70 with the regulation of CD4+.

Sericin Alleviates Thermal Stress Induced Anxiety-Like Behavior and Cognitive Impairment Through Regulation of Oxidative Stress, Apoptosis, and Heat-Shock Protein-70 in the Hippocampus.

Exposure to heat stress (HS) has adverse effects on brain function, leading to anxiety-like behavior and memory impairment. Sericin is a silk derived protein with various neurobiological activities. The present study has investigated the effects of sericin on anxiety and cognitive impairments, in HS-received mice. The adult male mice were exposed to HS (43 ºC, 15min once a day for 14days) and simultaneously treated with 100, 150, and 200mg/kg/day of sericin through oral gavage. Elevated plus-maze and Lashley III Maze tests were used to evaluate anxiety and learning and memory, respectively. The hippocampal BAX, BCL-2, caspase3, caspase9 and heat-shock protein-70 (HSP-70) were evaluated by western blotting and oxidative stress markers including malondialdehyde (MDA), total antioxidant capacity (TAC), super oxide dismutase (SOD) as well as glutathione peroxidase (GPx) were evaluated by spectroscopy method. The serum was collected for the analysis of the corticosterone levels. Treatment with sericin in higher doses reversed anxiety-like behavior and cognitive deficit induced by HS. Moreover, heat exposure increased serum corticosterone, hippocampal MDA, apoptotic proteins and HSP-70 levels. Sericin administration decreased serum corticosterone and enhanced hippocampal antioxidant defense and attenuated apoptosis and HSP-70 levels. The results show that the protective effects of sericin against HS-mediated cognitive dysfunction and anxiety-like behavior is possibly through suppressing HSP-70, oxidative stress and apoptosis.

Serum Heat Shock Protein 70 Level in Children with Attention Deficiency Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) have quite complicated etiology. The relationship between ADHD and immune and oxidative imbalances is discussed in current researches investigating the pathophysiology of ADHD. The aim of the study is to determine whether heat shock protein 70 (HSP70) has a potential role in pathophysiologic mechanisms of attention deficit hyperactivity disorder. This study included 41 children that were diagnosed with ADHD and 32 typically developing children. Conners' Teacher Rating Scale (CTRS) was used to evaluate ADHD presentation and severity. Additionally, an enzyme-linked immunosorbent assay (ELISA) kit was used to evaluate serum HSP70 level. We have detected that the serum HSP70 levels of children with ADHD were lower than the typically developing group (p<0.01). No relationship was determined between HSP70 levels and either the severity of ADHD or predominantly ADHD presentations (p>0.05). With these findings, it can be proposed that HSP70 might have a crucial role in the etiological mechanisms of ADHD. Moreover, these changes in peripheral blood may have therapeutic and/or diagnostic value. However, more detailed prospective studies are needed to explain the link between ADHD and heat shock proteins.

Serum heat shock protein 70 in preeclampsia and normal pregnancy: A systematic review and meta-analysis

Preeclampsia, a severe complication of human pregnancy is one of the main causes of maternal, fetal, and neonatal morbidity and mortality with unclear pathogenesis. Heat shock protein 70 (HSP70) is one of the factors that can mediate cytoprotective, antiapoptotic, and immune regulatory effects. This meta-analysis was performed with aim to evaluate HSP70 in preeclampsia and normal pregnancy. The original publications reporting the serum HSP70 levels in preeclampsia and normal pregnancies published before November 2015 were identified by searching PubMed Central, Scopus, and ISI Web of Knowledge databases by two researchers, separately. The keywords were" preeclampsia" and "HSP70" or "Heat shock protein 70" Statistical analyses were performed using STATA software (version 11). Out of 127 studies, seven eligible case-control studies were identified which consists of 350 preeclampsia and 429 normal pregnancies. Our pooled analysis of data from 7 studies which met the inclusion criteria, provides evidence that there is a significant association between HSP70 and preeclampsia. Cochran's test results showed the heterogeneity of the studies (p<0.001) and the I2 index was 91%. The standardized mean differences (SMD) based on a random effect model with trim and fill method was 0.92 (95% CI: 0.33-1.51); also there was a significant association between HSP70 and preeclampsia (Z=3.07, p=0.002). The results showed that serum HSP70 concentration was significantly higher in preeclamptic patients than the control group. Therefore HSP70 may be identified as a diagnostic factor.

Elevated serum heat shock protein 70 and liver stiffness reflect hepatic dysfunction and severity in postoperative biliary atresia.

Biliary atresia (BA) is a severe chronic liver disease characterized by progressive obstructive cholangiopathy of biliary tract. Heat shock protein 70 (HSP70) is involved in protecting cells against a wide variety of stress and plays a protective role in tissue damage. The purpose of this study was to investigate serum HSP70 and liver stiffness in BA and determine the association of serum HSP70, liver stiffness, and outcome parameters in post-Kasai BA patients. One hundred post-Kasai BA patients and 40 controls were enrolled. Serum HSP70 levels were analyzed using enzyme-linked immunosorbent assay. Liver stiffness values were assessed by transient elastography. BA patients had significantly higher serum HSP70 and liver stiffness values than controls. Serum HSP70 and liver stiffness values were markedly elevated in BA patients with jaundice compared to those without jaundice (P<0.001). Furthermore, serum HSP70 was more elevated in BA children with portal hypertension than those without portal hypertension (35.1±2.1 vs. 27.9±2.5ng/mL, P<0.001). Moreover, serum HSP70 was positively correlated with serum aspartate aminotransferase (r=0.491, P<0.001), alanine aminotransferase (r=0.448, P<0.001), total bilirubin (r=0.303, P=0.002), alkaline phosphatase (r=0.414, P<0.001), and liver stiffness values (r=0.455, P<0.001). There was a negative correlation between serum HSP70 and serum albumin (r=-0.434, P=0.001). Serum HSP70 and liver stiffness values were higher in BA patients than controls. The increased serum HSP70 was correlated with hepatic dysfunction in BA. Consequently, serum HSP70 and liver stiffness could serve as non-invasive parameters reflecting the severity in post-Kasai BA.

Diagnosis value of combined detection of serum golgi protein 73, desgamma carboxy prothrombin and α-fetoprotein in primary hepatic carcinoma

To analyze the clinical value of the detection of serum desgamma carboxy prothrombin (DCP), golgi glycoprotein 73 (GP73), heat-shock protein 70 (HSP70) in primary hepatic carcinoma (PHC) diagnosis. Enzyme-1inked immunosorbent assay and electrochemiluminescence immunoassay were used to detect the serum DCP, GP73, HSP70 and α-fetoprotein (AFP) levels in 35 PHC patients and 35 healthy controls. AFP, DCP and GP73 levels in PHC patients were 13.780 (1.140-8 487.000)µg/L, 3 213.953 (2.510-53 994.602)pg/ml and 76.838 (24.500-232.875)ng/ml respectively, significantly higher than those in healthy controls (1.240 (0.605-5.310)µg/L, 104.610 (0.000-4 138.770)pg/ml and 30.770 (16.343-87.453)ng/ml, U value were 134.50, 258.00 and 168.00, all P < 0.01); HSP70 could not be detected in any objects. The area under the ROC curve of DCP or GP73 was 0.789, 0.863 respectively. The sensitivity and specificity to PHC diagnosis were 54.3% and 97.1% by DCP (2 939.4 pg/ml as cut-off value), 85.7% and 74.3% by GP73 (41.3 ng/ml as cut-off value), 45.7% and 100% by AFP (20 µg/L as cut-off value). In combined detection the sensitivity, specificity and accuracy were 88.6%, 74.3%, 81.4% by GP73/AFP and 91.4%, 71.4%, 81.4% by GP73/DCP/AFP. GP73, DCP are new effective markers in the diagnosis of PHC, and the combined detection of GP73, DCP and AFP can improve the diagnosis value of PHC.

Elevated serum levels of heat shock protein 70 are associated with breast cancer.

Breast cancer (BC) is the most frequent cause of cancer death in women throughout the world. Thus, it is necessary to establish sensitive screening, diagnosis and treatment methods for BC. Heat shock protein 70 (HSP70) is an important cellular stress response protein that protects cells from apoptosis. Recent studies have shown that serum HSP70 levels may provide clinically important information in various types of cancer. HSP70 is also overexpressed in BC, which is known to be associated with cancer progression, apoptosis and cell proliferation. However, the serum level of HSP70 and its diagnostic and prognostic potential in BC have not been investigated yet. The aim of this study was to determine the usefulness of serum HSP70 level as a diagnostic test and its predictive value in patients with BC. This prospective study consisted of 45 female patients diagnosed with BC and 16 healthy women who were matched for age and body mass index (BMI). Enzyme-linked immunosorbent assay (ELISA) technique was used to measure the serum level of HSP70. The serum level of HSP70 was significantly higher in patients with BC than in the healthy control group (5.98 ± 2.05 vs. 1.49 ± 0.47 ng/ml, p = 0.001). HSP70 level > 2.41 ng/ml was the best cutoff value to predict BC (97.78% sensitivity and 93.75% specificity). This study shows that HSP70 can be used as an adjunct to other diagnostic tests for BC and may be helpful for identifying patients at increased risk of BC.

Heat shock protein 70 serum levels differ significantly in patients with chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

Members of the heat shock protein 70 (HSP70) family play an important role in assisting protein folding, preventing protein aggregation and transport of proteins across membranes under physiological conditions. Following environmental (i.e., irradiation, chemotherapy), physiological (i.e., cell growth, differentiation), and pathophysiological (i.e., inflammation, tumorigenesis) stress, the synthesis of heat shock proteins (HSPs) is highly up-regulated, whereas protein synthesis in general is reduced. In contrast to normal cells, many tumor entities including hepatocellular carcinoma (HCC) overexpress HSP70, the major-stress-inducible member of the HSP70 family, present it on their cell surface and secrete it into the extracellular milieu. Herein, the prognostic relevance of serum HSP70 levels in patients with chronic hepatitis (CH; n = 50), liver cirrhosis (LC; n = 46), and HCC (n = 47) was analyzed. Similar to other tumor entities, HSP70 is also present on the surface of primary HCC cells. The staining intensity of intracellular HSP70 in HCC tissue is stronger compared to control and cirrhotic liver sections. HSP70 serum levels in all HCC patients were significantly higher compared to a control group without liver disease (n = 40). No significant age- and gender-related differences in HSP70 serum levels were observed in male and female healthy human volunteers (n = 86). Patients with CH (n = 50) revealed significantly higher HSP70 serum levels compared to the control group, however, these values were significantly lower than those of HCC patients (n = 47). Furthermore, a subgroup of patients with LC who subsequently developed HCC (LC-HCC, n = 13) revealed higher HSP70 serum levels than patients with LC (n = 46, p = 0.05). These data indicate that serum HSP70 levels are consecutively increased in patients with CH, LC and liver carcinomas and thus might have a prognostic value.

Luteal serum BDNF and HSP70 levels in women with premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome characterized by psychological and somatic symptoms commencing in the luteal phase of the menstrual cycle and concludes with menstrual bleeding. PMDD affects 3-8 % of premenopausal women and represents a significant public health problem especially in young women. Decreased brain-derived neurotrophic factor (BDNF) levels are associated with several mental disorders. Heat-shock protein-70 (HSP70) is an important member of the molecular chaperone system, which provides a molecular defense against proteotoxic stress. We hypothesized that there would be changed levels of BDNF and HSP70 in women with PMDD compared with non-symptomatic women, reflecting impaired and/or activated stress-related responses involved in the underlying pathogenesis of PMDD. Female medical students were screened, and 24 women without premenstrual symptoms and 25 women with PMDD were enrolled in the study. Psychiatric evaluation and the Daily Record of Severity of Problems-Short Form were used for two consecutive menstrual cycles to diagnose PMDD. Serum BDNF and HSP70 levels were assessed in the third luteal phase. Participants with PMDD had significantly higher serum BDNF and HSP70 levels compared with controls, and there was a significant positive correlation between serum BDNF and HSP70 levels. Increased HSP70 levels may reflect cellular distress in PMDD. Increased serum BDNF levels in the luteal phase in subjects with PMDD may reflect a compensation process, which results in subsequent improvement of PMDD-associated depressive symptoms in the follicular phase. Thus, increased serum BDNF levels may be indicative of a compensating capacity in PMDD.

Abstract 18729: Serum Heat Shock Protein-70 is Associated With Decreased Frequency and Severity of Cellular Rejection in Cardiac Transplant Patients

Background: Heat Shock Protein-70 (HSP70) is a highly conserved intracellular protein that is up-regulated in cells undergoing stressful stimuli. A recent study demonstrated an inverse relationship between HSP70 expression and cellular rejection grade in endomyocardial biopsies (EBx)from cardiac transplant patients. Peripheral blood based HSP70 levels have not been studied in such individuals. We hypothesized that serum HSP70 levels will be associated with severity of cellular rejection in cardiac transplant patients. Methods: 177 cardiac transplant patients (56 ± 13 years; 8.5 ± 5 years mean time from transplant) were recruited from the Emory Cardiovascular Biobank from 2004-2012. Cellular rejection was defined based on revised International Society of Heart and Lung Transplant (ISHLT) grade of 1R or higher seen on EBx. Frequency of rejection was collected from time of transplant to enrollment date. Serum HSP70 was measured using ELISA and analyzed as detectable vs non-detectable. Nonparametric correlations and ANOVA were used to study univariate relationships while linear and ordinal logistic regression (adjusted for age, gender, race, length of time since transplant, and immunosuppressant medications) were performed to analyze the relationship between HSP70 levels and frequency and severity of cellular rejection respectively. Results: HSP70 was detectable in 35% of patients with grade 0R ISHLT class, 33% for grade 1R, 16% for Grade 2R, 0% for Grade 3R (p for group=0.005). There was an inverse correlation between HSP70 and frequency of rejection (r= -0.2, p= 0.03) with 34% of those with detectable HSP70 in the lowest quintile based on frequency of rejection whereas 9% was detected in the highest quintile (p=0.019). In adjusted regression models, HSP70 remained a significant independent predictor of a) ISHLT class with an OR of 0.43 (p=0.02) and b) frequency of rejection (β=-1.5, p=0.05). Conclusion: Detectable serum HSP70 is associated with decreased frequency and severity of cellular rejection in post cardiac transplant patients. The utility of HSP70 as a marker of graft function needs further study.

Serum Heat Shock Protein 70 Levels, Oxidant Status, and Mortality in Sepsis

Animal studies as well as prospective randomized clinical trials associated sepsis with redox imbalance and oxidative stress, but other studies failed to establish a correlation between antioxidant-based therapies and improvement of sepsis condition. This is also true for studies on the role of the chaperone heat shock protein 70 (HSP70), which is increased in serum during sepsis. Heat shock protein 70 is affected at several levels by oxidative stress, but this relationship has never been studied in sepsis. Here, we evaluated the relationship between serum HSP70 immunocontent and oxidant status in sepsis. Patients with severe sepsis were followed up for 28 days after diagnosis, or until death. Up to a maximum of 12 h after sepsis diagnosis, serum was collected for determination of HSP70 immunocontent by Western blot and evaluation of oxidative parameters (TRAP [total radical-trapping antioxidant parameter], TBARSs [thiobarbituric acid-reactive substances], and carbonyl levels). Serum of sepsis patients presented enhanced HSP70 levels. Analysis of oxidative parameters revealed that septic patients with pronounced oxidative damage in serum had also increased HSP70 serum levels. Sepsis patients in whom serum oxidative stress markers were not different from control presented normal serum HSP70. Analysis of septic patients according to survival outcome also indicated that patients with increased HSP70 serum levels presented increased mortality. We concluded that serum HSP70 levels are modulated according to the patient oxidant status, and increased serum HSP70 is associated to mortality in sepsis.

Parenteral glutamine increases serum heat shock protein 70 in critically ill patients

Heat shock protein 70 (HSP-70) is protective against cellular and tissue injury. Increased serum HSP-70 levels are associated with decreased mortality in trauma patients. Glutamine (Gln) administration increases serum and tissue HSP-70 expression in experimental models of sepsis. Gln has been safely administered to critically ill patients and can improve clinical outcomes, but the effect of Gln administration on HSP-70 expression in humans is unknown. We examined whether Gln-supplemented parenteral nutrition (PN) increases serum HSP-70 levels in critically ill patients. Randomized, controlled, double-blind study in surgical intensive care units (SICU) in a university hospital. 29 patients admitted to the SICU and requiring PN for more than 7 days. Patients received either Gln-PN (containing alanyl-glutamine dipeptide; 0.5 g/kg per day; n=15) or standard Gln-free PN (control-PN) that was iso-nitrogenous to Gln-PN (n=14). Serum HSP-70 concentrations were measured at enrollment and at 7 days. Clinical outcome measures were also determined. HSP-70 concentrations were unchanged in control-PN subjects from baseline to day 7. In marked contrast, Gln-PN subjects demonstrated significantly higher (3.7-fold) serum HSP-70 concentrations than control subjects. In Gln-PN patients there was a significant correlation between increases in HSP-70 levels over baseline and decrease in ICU length of stay. Gln-PN significantly increases serum HSP-70 in critically ill patients. The magnitude of HSP-70 enhancement in Gln-treated patients was correlated with improved clinical outcomes. These data indicate the need for larger, randomized trials of the Gln effect on serum and tissue HSP-70 expression in critical illness and relationship to clinical outcomes.

Association of High Intracellular, But Not Serum, Heat Shock Protein 70 With Postoperative Atrial Fibrillation

Atrial fibrillation is a common arrhythmia, after cardiac surgery. Reperfusion injury and inflammation associated with cardiac surgery are thought to be involved in its pathogenesis. We hypothesized that cytoprotective effects associated with heat shock protein 70 (HSP70) could counteract these proarrhythmic insults. We therefore set out to examine the influence of heat shock protein 70 on the incidence of postoperative atrial fibrillation. We prospectively recruited 80 patients undergoing elective coronary artery bypass surgery. Blood samples were collected preoperatively. Right atrial tissue was obtained at surgery. Incidence of postoperative atrial fibrillation and its duration were noted. Using a nested case-control design, 15 patients who developed atrial fibrillation were matched for operative procedure, age, sex, and beta-blocker usage, with 15 controls from the remaining patients. Atrial heat shock protein 70 was subsequently quantified by immunohistochemistry. Serum heat shock protein was measured using enzyme-linked immunosorbent assay and high sensitivity C-reactive protein was determined by immunoturbidometric assay. Intracellular HSP70 level was significantly higher in patients who did not develop atrial fibrillation (35 +/- 13 vs 19 +/- 15; p = 0.006). Atrial HSP70 level negatively correlated with atrial fibrillation; independent of other risk factors (odds ratio = 0.90; 95% confidence interval 0.84 to 0.99, p = 0.02). Serum HSP70 levels were similar in both groups (p = 0.81) and did not correlate with intracellular levels (p = 0.38). Preoperative C-reactive protein levels were similar in both groups (p = 0.93). Intracellular, but not serum, HSP70 level is negatively correlated with postoperative atrial fibrillation. This suggests a cardioprotective and an antiarrhythmic role for intracellular HSP70.