Plasma Fibronectin Concentrations Research Articles

Fibronectin as a Marker of Myocardial Remodeling in Patients with Depression and Chronic Heart Failure

Introduction Depression is a significant issue in chronic heart failure (HF), with a prevalence of about 20–40%, which is 4–5% higher than in the general population (Mbakwem A., et al., 2016).Objectives The purpose of this study was to evaluate plasma fibronectin levels in patients with depression and chronic heart failure.Methods A total of 80 patients with HF II-III NYHA classes due to chronic coronary artery diseases (CAD) were observed. All patients were divided into two groups: Group 1 - 20 individuals without signs of depression, and Group 2 - 60 individuals with depression. The diagnosis of HF was confirmed based on ESC guidelines (2021). Depression was diagnosed using several questionnaires (Zung Self-Rating Depression Scale, Beck Depression Inventory, Hamilton’s Depression Scale). Standard laboratory and instrumental tests were conducted. The plasma levels of fibronectin and interleukin-1β (IL-1β) were identified using ELISA methods. Statistical analyses were performed using Statistica system software, version 12.0.ResultsThe average plasma fibronectin concentration in patients with depression and HF was 1.24 times higher than a similar indicator in HF patients without depression: (259.63±5.71) μg/ml versus (203.41±9.51) μg/ml (p<0.05). The conducted correlation analysis indicated a moderate positive correlation between the level of fibronectin and the number of neutrophils in peripheral blood (r=0.35; p<0.05), the level of fibronectin and the magnitude of endogenous intoxication according to the erythrocyte absorption ability test (r=0.44; p<0.01), the level of fibronectin and IL-1β concentration (r=0.39; p<0.05), and an inverse correlation with left ventricle ejection fraction (r=0.32; p<0.05).ConclusionsThus, the plasma fibronectin content in patients with depression and ischemic HF serves as a marker of the progression of myocardial remodeling processes and the intensity of the inflammatory process.Disclosure of InterestNone Declared

Comparison of Vaginal and Plasma Fibronectin Concentrations for Prognosis of Preterm Delivery: A Cross-Sectional Study

Background & Objective: Prediction of preterm delivery can reduce a large number of its complications. The present study aimed to compare vaginal and plasma fibronectin concentrations in the diagnosis of preterm delivery.Materials & Methods: Serum samples were obtained from 105 women at 24-36 weeks of gestation. However, only 40 women gave permission to collect vaginal samples. Fibronectin concentration was measured using the ELISA technique. Then, plasma and vaginal fibronectin levels were compared in term and preterm deliveries.Results: The mean plasma fibronectin level was 6226.43±7174.97 ng/ml among the mothers with term infants and 7724.01±1143.82 ng/ml among those with preterm infants (p=0.667). The mean fetal fibronectin level was 156.61±126.42 ng/ml among the mothers with term infants and 127.71±43.14 ng/ml among those with preterm infants (p=0.241). The cut-off point of plasma fibronectin level was 1750 ng/ml with a sensitivity of 80.25% and specificity of 85.17%. Additionally, the cut-off point of vaginal fibronectin level was 158.98 ng/ml with a sensitivity of 94.62% and specificity of 22.08%.Conclusion: Plasma fibronectin analysis had lower sensitivity and higher specificity compared to vaginal fibronectin analysis. This implies that plasma testing has lower false-positive cases and can identify a more significant number of true positive cases of preterm delivery.

UCHL1, besides leptin and fibronectin, also could be a sensitive marker of the relapsing–remitting type of multiple sclerosis

Research on the markers of immunoregulatory response in multiple sclerosis (MS) is still of great importance. The aim of our study was the evaluation of leptin, fibronectin, and UCHL1 concentrations as potential biomarkers of a relapsing–remitting type of MS (RRMS). Surface Plasmon Resonance Imaging (SPRI) biosensors were used for the evaluation of proteins concentrations in 100 RRMS patients and 46 healthy volunteers. Plasma leptin, fibronectin, and UCHL1 concentrations were significantly higher in RRMS patients compared to the control group (p < 0.001, respectively). UCHL1 concentration evaluation revealed the highest diagnostic sensitivity (100%) and negative predictive value (100%) in differentiating MS patients from healthy individuals. There was no significant difference in the UCHL1 concentrations depending on the patient’s sex, the presence of relapse within the last 24 months, and the EDSS value (p > 0.05, respectively). In RRMS patients UCHL1 concentration positively correlated with fibronectin levels (r = 0.3928; p < 0.001). In the current cohort of patients plasma UCHL1 concentration was independent of the time of MS relapse and the severity of neurological symptoms. Thus current study may indicate that plasma UCHL1, besides leptin and fibronectin, also could be a promising high-sensitive potential biomarker of relapsing–remitting type of MS. However, these results should be validated with a larger group of patients, taking into account neuroimaging and cerebrospinal fluid analysis data, and by comparing them to patients with other neurological diseases as a control group.

Fibronectin: structure, functions, clinical significance (review)

Plasma fibronectin is a high molecular weight adhesive glycoprotein. There are two types of fibronectin: plasma (soluble) and cellular derived (insoluble). Electron microscopy revealed two types of structural organization of fibronectin: compact and expanded. In solution, fibronectin has a compact conformation, and after binding to certain substrates (collagen, fibrin, heparin), it is expanded. Plasma fibronectin is one of the main opsonins of blood plasma in relation to the “targets” of phagocytosis of a predominantly non-bacterial nature, as well as to some types of bacteria. For the treatment of septic processes, as well as respiratory distress syndrome of adults with severe fibronectin deficiency, plasma cryoprecipitate is used – a donor plasma preparation containing a large amount of plasma fibronectin (more than 2 mg/ml). It was proposed to replenish the level of fibronectin in patients with sepsis and other conditions that cause plasma fibronectin deficiency with the help of donor freshly frozen plasma. Transfusion of large volumes of freshly frozen plasma (up to 1000–1500 ml) to patients effectively eliminates the deficiency of plasma fibronectin. The concentration of plasma fibronectin in the blood significantly decreases after the addition of severe infectious processes to hematological diseases, as well as acute DIC syndrome. Extracorporeal methods of blood purification – selective plasmapheresis – have been developed to correct immunocomplex and fibronectin-complex pathology. Two variants of selective plasmapheresis have been proposed: the method of heparinocryoprecipitation of plasma proteins and the method of heparinocryofractionation. In 1987, a plasma heparin precipitate was proposed as a source of fibronectin for the treatment of patients with trophic skin lesions. In 1992, a new method was proposed for obtaining blood preparations with a high concentration of plasma fibronectin from patients themselves (heparin cryofractionation). Autofibronectin preparations obtained by such methods are effective in the local treatment of trophic ulcers in 90–93% of cases. The proposed drugs are safe against infection of patients with infectious diseases transmitted through the blood.

Changes of plasma fibronectin and fibronectin-fibrin complexes in dams of stillborn dairy calves

BackgroundFibronectin (FN) is a large (450–500 kDa), multidomain and multifunctional glycoprotein existing in mammalian tissues. Some fibronectin (FN) molecular forms might be involved in biological processes occurring within the perinatal period, such as tissue remodeling, coagulation, and repair.ResultsIn this study fibronectin (FN) and fibrinogen (Fb) concentrations and FN-fibrin complexes occurrence and its relative amounts with increasing high molecular masses were respectively determined by ELISA, heat precipitation, and SDS-agarose-immunoblotting methods. Plasma samples from three groups of dams with: 1) singleton stillborn calf without or with negligible autolytic changes in internal organs (DSBn), 2) singleton stillborn calf with advanced autolytic changes in internal organs (DSBa), 3) singleton live-born control calf (DC), and 4) a group of cows during mid to late lactation (LC) were analyzed. Maternal plasma FN concentration in the DSBn and DSBa groups was significantly lower than in the LC group. The plasma samples of DSBa showed a significantly lower FN concentration than in the DC group. Plasma Fb concentration was significantly higher in the DSBa and DSBn, than in the LC group. FN immunoblotting of the cow plasma samples revealed, besides an FN-dimer band, the presence of supramolecular FN-fibrin bands corresponding to FN-fibrin complexes with increasing molecular masses: up to 5 bands from 750 kDa to 1900 kDa in the DSBn and DSBa plasma samples, two bands of 750 and 1000 kDa in the DC group, and only the smallest one of 750 kDa in the LC group.ConclusionsThe observed low FN concentration and occurrence of supramolecular FN-fibrin complexes (1000 kDa and more) in the maternal plasma comparing to cows in lactation might have been associated with periparturient changes in tissues. The presence in maternal plasma of high-molecular FN-fibrin complexes (1300–1900 kDa) arouse the question if this is the consequence of calf perinatal mortality.

The comparison of plasma fibronectin in term and preterm delivery: A cross-sectional, descriptive-analytical study.

BackgroundPreterm delivery is one of the main causes of infant death. Therefore, prediction of preterm delivery may eliminate a large number of prenatal complications.ObjectiveThe present study aimed to understand if preterm delivery can be predicted by assessing maternal plasma fibronectin concentration.Materials and Methods Serum samples from 105 pregnant women participating in this study were collected. The plasma fibronectin were measured at 24-28 wk of gestation and again at 32-36 wk of gestation. Unfortunately, only 65 of the 105 pregnant women, returned for the second sampling. The plasma fibronectin was analyzed using ELISA method and its concentration in term and preterm deliveries was compared. The delivery dates of all the women were also recorded.ResultsOut of 105 pregnant women, 28 delivered preterm (26.7%). The Plasma fibronectin concentrations in women with preterm delivery were higher than in those who delivered at term (p = 0.001). Accordingly, Plasma fibronectin concentrations were significantly higher in the second serum samples (p = 0.01). Plasma fibronectin concentrations was also higher in obese women and in those suffering from preeclampsia (p = 0.12) and gestational diabetes (p = 0.81).ConclusionPlasma fibronectin concentrations test could be used as an optional screening test for preterm delivery at 28 to 34 wk of gestation in pregnant women who prefer to avoid vaginal sampling.

Delivery-associated presence of supramolecular fibronectin-fibrin complexes in puerperal and cord plasma

Objective: The variable fibronectin (FN) molecular forms are known to be engaged in coagulation and fibrinolysis pathways as well as tissue remodeling and repair processes. Some of them seem to be indispensable molecules within intensive biological processes associated with delivery. The aim of the study was to evaluate the FN molecular status in maternal and cord plasma after vaginal birth and cesarean section (C-section).Materials and methods: The study included nonpregnant women’s plasma samples (n = 31) and puerperal and cord plasma samples collected from 49 mothers who delivered healthy newborns at term by vaginal birth (n = 25) and C-section (n = 24). The maternal and cord plasma FN concentrations and presence and relative ratios of different FN-fibrin complexes were determined by ELISA and sodium dodecyl sulfate (SDS) -agarose immunoblotting, respectively.Results: FN concentration in puerperal plasma after vaginal birth (232.08 ± 71.8 mg/L) and C-section (228.17 ± 71.2 mg/L) was significantly higher than in the plasma of nonpregnant women (190.00 ± 48.75 mg/L). In contrast, FN concentration in cord plasma of the C-section group (101.95 ± 30.3 mg/L) was significantly lower than that of the vaginal birth group (121.80 ± 22.2 mg/L). Immunoblotting of puerperal and cord plasma distinguished the most abundant dimeric plasma FN form, the 220–280-kDa FN degradation products and 750–1900-kDa FN-fibrin complexes, which occurred more frequently and in higher amounts in puerperal and cord plasma groups than the nonpregnant women group, although independently of the mode of delivery.Conclusions: Occurrence and relative amount of delivery-associated FN–fibrin complexes in both puerperal and cord plasmas might be bound with the physiological adaptive mechanisms reducing the risk of hemorrhage and intensive remodeling and repair processes after delivery.

SPR imaging biosensor for the quantitation of fibronectin concentration in blood samples

The purpose of this study was presentation of a new biosensor capable of determination of fibronectin. This biosensor was based on the specific interaction of anti-fibronectin antibody produced in rabbit with fibronectin. The surface plasmon resonance imaging (SPRI) technique was used as a detecting method. Optimization and characterization properties of the biosensor were studied. The determination of fibronectin concentration in natural samples was done. The results were compared with a reference method (Enzyme-Linked Immunosorbent Assay-ELISA). The analytically useful dynamic response range of biosensor is between 5 and 400ngmL−1. The detection limit is 1.5ngmL−1 and limit quantification is 5ngmL−1. The proposed SPRI biosensor showed good selectivity for potential interferences. It was applied to determine fibronectin concentrations in plasma of healthy donors and of patients after thermal injury. Good correlations between results obtained using the SPRI biosensor and ELISA test (correlation coefficients for healthy donors 0.996, for patients 0.984) were obtained. The average fibronectin concentration of healthy donors was 140.5±24.6μgmL −1 and the average fibronectin concentration of patients was 601.5±72.1μgmL −1, which was in agreement with results obtained by other investigators. The obtained results indicate that the developed biosensor may be a candidate for monitoring fibronectin concentration in blood samples.

Plasma concentration of fibronectin is decreased in patients with hypertrophic cardiomyopathy

ObjectivesTo confirm the initial iTRAQ-based proteomic findings related to the plasma fibronectin level and hypertrophic cardiomyopathy using an antibody-based assay. MethodsThe iTRAQ technique was used for the discovery proteomic analysis of the pooled plasma samples. The ELISA was used for verification of fibronectin plasma concentration in individual samples. Additional five related plasma proteins were assessed: matrix metalloproteinase 2, matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 1, tissue inhibitor of metalloproteinase 2 and brain natriuretic peptide. ResultsThe plasma fibronectin level in patients with hypertrophic cardiomyopathy was significantly lower in comparison to the healthy subjects [215.5±47.3μg/ml, n=17 vs. 376.7±134.8μg/ml, n=17; p<0.0001]. ConclusionIn this study we present and confirm our initial proteomic findings and we suggest fibronectin as a potential indicator of an extracellular matrix remodeling related to the hypertrophic cardiomyopathy.

Role of fibronectin under conditions of doxorubicin action

There is no standard as to treatment of anthracycline chemotherapy complications. The reduction of cytotoxic drugs toxicity without weakening of their antitumor action remains relevant. The extracellular matrix which key component is fibronectin is present in all tissues and it continuously undergoes controlled remodeling. So, the purpose of our work was to study the level of fibronectin in the experimental model of doxorubicin-induced cardiomyopathy and effects of this cytostatic and its co-administration with antioxidants of different nature.The level of fibronectin was measured by ELISA using monospecific antibodies against fibronectin (Sigma, USA), secondary anti-IgG labeled with horseradish peroxidase (Sigma, USA) and fibronectin standard (Sigma, USA). The study was conducted on Wistar male rats with weight of 210 ± 50 g which were divided into 4 groups by 8 animals in each group: 1 – control, rats receiving saline i/p; 2 – doxorubicin 1 mg/kg i/p once a week during 4 weeks; 3 – doxorubicin by the same scheme plus 1% 2-oxoglutarate in drinking water during 4 weeks;4 – doxorubicin by the same scheme and korvitin injection 30 min before doxorubicin application once a week during 4 weeks. Obtained data indicate the effect of doxorubicin to decrease in index mass heart in 38% of animals compared to control animals; decrease in total protein concentration by 8% (Р &lt; 0,05) and increase of the level of fibronectin by 67% (P &lt; 0,001) in blood plasma of rats and decrease in the level of fibronectin in the heart extract by 19% (Р &lt; 0,05) under development of doxorubicin-induced cardiotoxicity. Increased fibronectin concentration in blood plasma had strong correlation with decreased total protein concentration in blood (r=0,80) and heart extract (r=0,59) in rats with doxorubicin-induced cardiomiophaty indicating the sensitive reaction of fibronectin to development of metabolic disorders under doxorubicin influence.

Сіальованість глікопротеїнів і рівень експресії нейрамінідази NEU1 та сіалілтрансферази ST6GAL1 у лімфоцитах хворих на еритремію

We studied the levels of lymphocyte surface-associated sialylglycans and the expression of neuraminidase NEU1 and sialyltransferase ST6GAL1 genes in lymphocytes in erythremia patients and healthy donors as well as the levels of sialic acids in plasma and sialylation of alpha-acid glycoprotein and fibronectin. Moreover, we also investigated the type of sialic acids binding with its glycans using sialospecific lectins MAA and SNA. fibronectin protein in lymphocytes and its cell surface in erythremia disease as compared to healthy donors. It was shown that the levels of free sialic acids and neuraminidase activity in plasma are increased in erythremia disease as compared to healthy donors; however, MAA-II-binding activity of tested glycoproteins is decreased, fibronectin-1 mRNA expression in lymphocytes is increased in patients with erythremia. The decreasing of plasma fibronectin concentration and its heparin-binding activity as well as increasing of lymphocyte content with surface-associated and intracellular fibronectin were revealed in erythremia disease in comparison with healthy donors. Positive correlation between plasma fibronectin level and its heparin-binding activity and negative correlation between plasma fibronectin level and quantity of lymphocytes which express fibronectin inside the cell and on cell surface was detected. Enhanced levels of α2,3- and α2,6-linked residues of glycocojugates were detected on lymphocyte cell surface in erythremia disease using sialospecific lectins and flow cytometer as well as fluorescent confocal microscope. The level of NEU1 and ST6GAL1 mRNA expressions is significantly increased in lymphocytes in erythremia disease. Results of this study are clarified the mechanisms of disturbed in erythremia disease glycobiological processes and may therefore present new approaches for therapeutic opportunities.

Plasma Fibronectin Concentration in Obese/Overweight Pregnant Women: A Possible Risk Factor for Preeclampsia

Plasma fibronectin (FN) levels in obese/overweight and non-obese pregnant women were evaluated as a possible risk factor for preeclampsia. A total of one hundred and sixty three pregnant women attending antenatal clinic at University of Calabar Teaching Hospital participated in the study and sixty non-pregnant women served as control. About 77 (47.24%) of the pregnant women were followed up for any subsequent development of preeclampsia during the pregnancy. Fibronectin levels in plasma were measured by ELISA assay and serum total protein, urea and creatinine were determined spectrophotometrically. The mean plasma FN concentration of non-obese pregnant women in first trimester was lower than those of the non-pregnant women by 24%, but however, increased to the non-pregnant level in second and third trimesters. Obese/overweight pregnant women had significantly (P<0.05) higher values than non-obese pregnant women in second and third trimesters. FN in obese/overweight pregnant women correlated positively with mean arterial blood pressure (MAP: r=0.414, P=0.04). About 28.57% of the pregnant women with FN above cut off point of 330μg/ml at 18-24weeks of gestation developed preeclampsia. This value increased to 40.0% when only the obese/overweight women were considered. On analysis of both fibronectin >330μg/ml and MAP>90, the predictive value increased to 66.7%. We therefore conclude that elevated FN may be regarded as a risk factor of preeclampsia especially among the obese women.

Зміна гепарин- і лектин-зв’язувальної активності фібронектину при проліферативних захворюваннях крові

Fibronectin concentration, its heparin-binding activity and interaction with Lens Culinaris Agglutinin (LCA), Aleuria Aurantia Lectin (AAL) and Laburnum Anagyroides Agglutinin (LABA) in patients with erythremia and subleukemic myelosis were investigated. Reliable decreasing of concentration and heparin-binding activity of plasma fibronectin as well as a connection between its functional activity and lectin-affinity were detected. Increasing of the level of core fucose in N-glycans of fibronectin in proliferative blood diseases was revealed. Presence of fucose in O-glycans of fibronectin and dependence of fucosylation level of O-glycans in the glycoprotein on the type of pathological processes were proved. Keywords: fibronectin, heparin, lectin, fucose, erythremia, subleukemic myelosis.

Plasma osteopontin concentrations in preeclampsia – is there an association with endothelial injury?

Abstract Background: It has been previously reported that plasma osteopontin (OPN) concentrations are increased in cardiovascular disorders. The goal of the present study was to determine plasma OPN concentrations in healthy pregnant women and preeclamptic patients, and to investigate their relationship to the clinical characteristics of the study subjects and to markers of inflammation [C-reactive protein (CRP)], endothelial activation [von Willebrand factor antigen (VWF:Ag)] or endothelial injury (fibronectin), oxidative stress [malondialdehyde (MDA)] and trophoblast debris (cell-free fetal DNA). Forty-four patients with preeclampsia and 44 healthy pregnant women matched for age and gestational age were involved in this case-control study. Plasma OPN concentrations were measured with ELISA. Serum CRP concentrations were determined with an autoanalyzer using the manufacturer's reagents. Plasma VWF:Ag was quantified by ELISA, while plasma fibronectin concentrations were measured by nephelometry. Plasma MDA concentrations were estimated by the thiobarbituric acid-based colorimetric assay. The amount of cell-free fetal DNA in maternal plasma was determined by quantitative real-time PCR analysis of the sex-determining region Y (SRY) gene. For statistical analyses, non-parametric methods were applied. Serum levels of CRP, as well as plasma concentrations of VWF:Ag, fibronectin, MDA and cell-free fetal DNA were significantly higher in preeclamptic patients than in healthy pregnant women. There was no significant difference in plasma OPN concentrations between controls and the preeclamptic group. However, preeclamptic patients with plasma fibronectin concentrations in the upper quartile had significantly higher plasma OPN concentrations than those below the 75th percentile, as well as healthy pregnant women [median (interquartile range): 9.38 (8.10-11.99) vs. 7.54 (6.31-9.40) and 7.40 (6.51-8.80) ng/mL, respectively, p<0.05 for both]. Furthermore, in preeclamptic patients, plasma OPN concentrations showed a significant positive linear association with plasma fibronectin (Spearman R=0.38, standardized regression coefficient (beta)=0.41, p<0.05 for both). Plasma OPN concentrations are increased in preeclamptic patients with extensive endothelial injury. However, further studies are warranted to explore the relationship between OPN and endothelial damage. Clin Chem Lab Med 2010;48:181-7.

Circulating anti-heat-shock-protein antibodies in normal pregnancy and preeclampsia

It has been previously reported that circulating anti-heat-shock-protein (Hsp) antibody levels are elevated in cardiovascular disorders. The aim of the present study was to determine circulating antihuman Hsp60, antimycobacterial Hsp65, and antihuman Hsp70 antibody levels in healthy pregnant women and preeclamptic patients and to investigate their relationship to the clinical characteristics of the study subjects, as well as to the markers of inflammation (C-reactive protein (CRP)), endothelial activation (von Willebrand factor antigen), or endothelial injury (fibronectin), oxidative stress (malondialdehyde) and to serum Hsp70 levels. Ninety-three preeclamptic patients and 127 normotensive healthy pregnant women were involved in this case control study. Serum anti-Hsp60, anti-Hsp65, anti-Hsp70, and Hsp70 levels were measured with enzyme-linked immunosorbent assay (ELISA). Serum CRP levels were determined by an autoanalyzer using the manufacturer's kit. Plasma von Willebrand factor antigen levels were quantified by ELISA, while plasma fibronectin concentration by nephelometry. Plasma malondialdehyde levels were measured by the thiobarbituric-acid-based colorimetric assay. For statistical analyses, nonparametric methods were applied. Anti-Hsp60, anti-Hsp65, and anti-Hsp70 antibodies were detected in all of our serum samples. There were no significant differences in serum anti-Hsp60, anti-Hsp65, and anti-Hsp70 antibody levels between the control and preeclamptic groups. Serum levels of Hsp70 and CRP, as well as plasma levels of VWF antigen, fibronectin, and malondialdehyde, were significantly higher in preeclamptic patients than in normotensive healthy pregnant women. Serum anti-Hsp60 antibody levels showed significant correlations with serum anti-Hsp65 antibody levels both in the control and the preeclamptic groups (Spearman R = 0.55 and 0.59; p < 0.001, respectively). However, no other relationship was found between clinical features (maternal age, smoking status, parity, body mass index, gestational age at blood draw, systolic and diastolic blood pressure, gestational age at delivery, and fetal birth weight) and measured laboratory parameters of the study subjects and serum anti-Hsp antibody levels in either study group. In conclusion, anti-Hsp60 and anti-Hsp70 antibodies as naturally occurring autoantibodies are present in the peripheral circulation of healthy pregnant women. Nevertheless, humoral immunity against heat shock proteins was not associated with preeclampsia. Further studies are warranted to explore the role of heat shock proteins and immune reactivity to them in the immunobiology of normal pregnancy and preeclampsia.

Plasma fibronectin concentration in inbred mouse strains

Plasma fibronectin concentration in inbred mouse strains

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

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.

Follow-up of the serum levels of extracellular matrix components in acute and chronic pancreatitis

Time-dependent serum concentrations of extracellular matrix proteins were studied in 32 patients with pancreatitis in order to find potential markers of the reparative response during the disease. Patients were subdivided by clinical and biochemical criteria: severe acute pancreatitis (n = 10), moderate acute pancreatitis (n = 17), and acute attack of chronic pancreatitis (n = 5). Serum and plasma samples were collected on days 1-7, 10, 14, and 21 for measurements of the aminoterminal propeptide of type III procollagen (PIIINP), hyaluronic acid, laminin, fibronectin, and routine clinical-chemical parameters. During an acute attack of chronic pancreatitis all parameters were within the reference range. In moderate acute pancreatitis concentrations of PIIINP, laminin, and hyaluronic acid fluctuated around the upper reference limit, but declined to mid-normal levels at day 21. In severe acute pancreatitis all three parameters increased. In patients who died as a consequence of sepsis and multi-organ failure the increase in PIIINP, laminin and hyaluronic acid was much more pronounced and paralleled by a decrease in plasma concentrations of fibronectin. In conclusion, this study revealed a relation between the severity of acute pancreatitis and the increase in serum concentrations of extracellular matrix components, especially PIIINP.

Reduced plasma fibronectin in patients with sepsis and shock (author's transl)

Plasma fibronectin concentrations were determined in 16 patients with sepsis and shock. In all patients a definite decrease was observed during the course of the disease which did not correlate with coagulative function. Fibronectin in plasma rose to normal levels with improvement in the clinical picture. It is possible that plasma fibronectin indicates the functioning of the reticuloendothelial system.

Minute changes in composition of polymer substrates produce amplified differences in cell adhesion and motility via optimal ligand conditioning

We explored the interplay between substratum chemistry of polymeric materials and surface-adsorbed ligand concentration (human plasma fibronectin) in the control of cell adhesion and cell motility. We found that small changes in the chemical composition of a polymeric substratum had different effects on cellular motility—depending on the concentration of preadsorbed fibronectin. We used two tyrosine-derived polyarylates, poly(DTD diglycolate) and poly(DTD glutarate), as substrata for the seeding of NIH-3T3 fibroblasts. The only compositional difference between the two test polymers was that one single oxygen atom in the polymer backbone of poly(DTD diglycolate) had been substituted by a methylene group in the backbone of poly(DTD glutarate), The two polymers had closely matched hydrophobicity and physical properties. Flat, spin-coated surfaces of these polymers were pretreated with different concentrations of human plasma fibronectin (0–20 μg/ml). After seeding with NIH-3T3 fibroblasts, we examined the adhesion and motility behavior of these cells. We found that NIH-3T3 fibroblasts migrated significantly faster on poly(DTD diglycolate), but only when the polymer surfaces were pretreated with intermediate concentrations of fibronectin. Only at these intermediate levels of ligand conditioning, did the presence of an extra oxygen atom in the backbone of poly(DTD diglycolate) relative to poly(DTD glutarate) (i) alter the overall organization/concentration of the fibronectin; (ii) weaken cell attachment strength and inhibited excessive cell spreading; and (iii) promote cell motility kinetics. These findings indicate that the biological effect of minute changes in substratum chemistry is critically dependent on the level of surface-adsorbed cell-binding ligands.