Plasma Fibronectin Levels Research Articles

Plasma levels of fibronectin bearing the alternatively spliced EIIIB segment are increased after major trauma

Using Western-blot analysis and enzyme-linked immunosorbent assay (ELISA) of N-deglycosylated samples, we have observed that plasma levels of fibronectin (FN) bearing the alternatively spliced EIIIB segment (EIIIB + FN) increase in patients after admission to the intensive-care unit (ICU) for acute major trauma. Although not increased at the first sampling (“0 hour”), taken within 24 hours of ICU admission, levels measured 24, 48, and 72 hours later were significantly increased compared with levels obtained in healthy controls. Furthermore, average concentrations at these latter time points were significantly increased relative to the 0-hour sampling. EIIIB + FN levels then decreased in plasma samples taken 1 month after hospital discharge, such that no significant difference was found between ELISA-measured values at this time and 0 hour or control values. On the basis of comparisons with previous measurements in these samples, it is apparent that after acute major trauma, circulating levels of soluble EIIIB + FN exhibit temporal changes that are qualitatively similar to those encountered for FN isoforms bearing the alternatively spliced EIIIA segment (EIIIA + FN), yet different from those observed for the total pool of circulating FN. This is the first report of measurement of FN in clinical plasma samples with antibodies specific for the highly conserved EIIIB segment. Like EIIIA + forms of FN, EIIIB + FNs are recognized as soluble bloodborne markers for vascular tissue injury.

DETERMINATION OF PLASMA FIBRONECTIN AND SERUM C‐REACTIVE PROTEIN IN PATIENTS WITH CEREBROVASCULAR EVENTS

SUMMARYThe relationship between the levels of C‐reactive protein (CRP) and fibronectin (FN) and atherosclerotic diseases such as coronary heart disease has already been studied, but their relationship with cerebrovascular events has not. The aim of this study was to determine the levels of plasma FN and serum CRP in cerebrovascular events, and their relationship with the outcome of the disease. CRP and FN levels were analysed in 133 patients with acute cerebrovascular disease, together with 66 healthy controls. Cerebrovascular event patients were divided into subgroups according to disease severity. FN and CRP levels in patients with cerebrovascular disease were found to be significantly elevated compared with the control group (p<0.001). CRP levels correlated with disease severity, in contrast to FN levels. We conclude that FN is not a clinically useful marker in patients with acute differentiative cerebrovascular events, in contrast to CRP which may be useful in such cases.

Clinical and experimental studies on fibronectin in bronchial asthma

Clinical and experimental studies were performed to investigate the kinetics of fibronectin (FN) and its clinical significance in bronchial asthma. Measurements of plasma fibronectin (PFN) and sputum fibronectin (SFN) were performed in asthmatic patients. Eosinophil chemotaxis, adherence and activation activity to FN were measured. An animal model of bronchial asthma was created and lung tissues were analyzed by immunohistochemical staining. Compared with periods without an asthmatic attack, the PFN level was significantly lower during periods with more severe asthmatic attacks in 15 patients with bronchial asthma. In contrast, the SFN level was significantly higher during periods with more severe asthmatic attacks. In a guinea pig model of asthmatic bronchitis, FN was positively stained in the subepithelial or submucosal tissue and abraded epithelial cells in the alveolar space during asthmatic attacks. Marked eosinophilic infiltration was also noted in the same tissues and cells. A negative correlation was noted between the number of peripheral eosinophils and the PFN level. In contrast, a positive correlation was noted between the number of sputum eosinophils, which reflects the severity of asthmatic attacks, and the SFN level. An experimental study was performed to investigate the relationship between eosinophils and FN. A positive relationship was noted between eosiophil chemotaxis, increased adherence of activated eosinophils and FN levels. It is suggested that FN may enhance allergic reactions at an early or acute phase of bronchial asthma.

Plasma fibronectin level and its relationships with lipids, lipoproteins and C-reactive protein in patients with dyslipidaemia during lipid-lowering therapy

Objectives — The purpose of this study is to determine plasma fibronectin level and its relationships with plasma lipids, lipoproteins and C-reactive protein (CRP) levels in patients with dyslipidaemia during lipid-lowering therapy.Methods — Plasma levels of fibronectin, CRP, fibrinogen, lipids and lipoproteins in 38 patients with dyslipidaemia were determined before and after lipid-lowering therapy by using atorvastatin, 10 mg/day.Results — After lipid-lowering therapy, serum levels of fibronectin and CRP were found to be significantly decreased by 30.4% and 43,6%, respectively, while fibrinogen levels were increased 11.7% in patients with dyslipidaemia. Before the treatment, fibronectin was found to be positively correlated with CRP and total cholesterol (r=0.38, p<0.05 and r=0.33, p<0.05, respectively) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) (r=–0.42, p<0.01) in patients with dyslipidaemia. High fibronectin levels (0.57±0.17 g/l) were found in patients with HDL-C below 35 mg/dl (0.57±0.09 g/l), compared to patients with HDL-C above 35 mg/dl (0.45±0.11 g/l). During the lipidlowering therapy, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and apo B levels were reduced while HDL-C and apo AI levels were increased.Conclusions — It was found that plasma fibronectin and CRP levels were decreased by lipid lowering therapy. Plasma fibronectin levels were associated with lipids, lipoproteins, CRP levels before treatment and these relationships disappeared after treatment. Consequently, it was suggested that reduction of plasma fibronectin levels, together with lipids and loss of its relationship with CRP, may play a role on the antiatherogenic effects of lipid-lowering therapy.

Detection of endothelial dysfunction in preeclamptic patients by using color Doppler sonography.

Our goal in this study was to detect endothelial function in normal and preeclamptic patients by using color Doppler sonography and plasma fibronectin levels. The increased ratio of the brachial artery diameter during shear stress, and plasma fibronectin levels were measured in 15 preeclamptic and 11 normal, gestational-age matched pregnant patients. The test was repeated at the postpartum second and sixth weeks in the preeclamptic group. In addition, the plasma fibronectin levels of all patients were measured. The increased ratios were 4.26+/-0.69% vs 12.18+/-1.97% in the preeclamptic and normal patients, respectively ( P=0.003). At the second and sixth postpartum weeks, the ratios were 6.67+/-0.89% and 9.27+/-1.16% in the preeclamptic group, revealing a significant improvement in the sixth week ( P=0.001). Fibronectin levels were 0.80+/-0.11 g/L vs 0.45+/-0.06 g/L in preeclamptic and normal patients ( P=0.01). The correlation coefficient between the fibronectin levels and increase rate was r=-0.38 and P=0.05. We conclude that endothelial dysfunction, which is fundamental to preeclampsia, can be detected by using color Doppler sonography.

Increased plasma fibronectin levels in patients with acute myocardial infarction complicated with left ventricular thrombus

Fibronectin is a polymorphic and multifunctional glycoprotein that plays a wide-ranging role in hemostasis. In this study, it was aimed to determine plasma fibronectin levels and evaluate its possible role in left ventricular (LV) thrombus formation following acute myocardial infarction (AMI). We have determined clinical, echocardiographic, and biochemical parameters in 97 consecutive patients (aged 59±13; 87 men/10 women) with first anterior AMI. Two-dimensional echocardiography was performed on Days 1, 3, 7, 15, and 30. Blood samples were obtained within 24–48 h after the onset of symptoms. The study also included 30 healthy control subjects. Plasma fibronectin levels were significantly higher in patients with AMI than control subjects (38±13 vs. 25.2±8.7 mg/dl, P=.0001). LV thrombus was detected in 20 (20.6%) of 97 patients. Plasma fibronectin levels were significantly higher in patients with LV thrombus (Group 2) than in patients without LV thrombus (Group 1) (44.5±11 vs. 36.1±13.4 mg/dl, P=.01). Although univariate analysis showed that plasma fibronectin levels were higher in patients with thrombus, multivariate analysis showed that plasma fibronectin levels were not an independent predictor of LV thrombus formation ( P=.059). In multivariate analyses, only peak creatine phosphokinase (CPK) level and LV wall motion score index (WMSI) were independent predictors of thrombus formation ( P=.007 and P=.0001, respectively). These results suggest the increased plasma fibronectin levels may be one of the risk factors for LV thrombus formation after AMI. However, further studies concerning the relation between plasma fibronectin levels and LV thrombus formation are necessary.

Triglycerides Predict Plasma Fibronectin in Children with Type I Diabetes Mellitus Rather than Diabetes

Fibronectins are adhesive proteins considered as markers of endothelial activation. Plasma fibronectin levels in diabetes mellitus (DM) have been found to be associated with atherosclerotic risk factors. This study was carried out to investigate plasma fibronectin and its relation with serum lipids, apolipoproteins AI, B100 and lp(a) in diabetic children. 35 children (19F/16M) with type I DM and 30 non-diabetic age and gender-matched controls were enrolled. Apolipoprotein and fibronectin concentrations were determined with nephelometric methods. Plasma fibronectin levels of the children with type I DM and the control group are not statistically different. HbA1c and triglycerides concentration are found to be significant predictors of plasma fibronectin in diabetic children, while effect of plasma cholesterol, apolipoprotein AI, B100 and lp(a) are insignificant. Diabetic children with triglycerides 1.13 mmol/l have elevated plasma fibronectin (median, 25th-75th percentiles; 29.6, 8.3-40.8 mg/dL) compared to the diabetic > or = 19.9, 8.6-30.7 mg/dL, p < 0.05) and non-diabetic children (16.6, 12.7-32.4 mg/dL, p < 0.01) with triglycerides < 1.13 mmol/L. On the other hand plasma fibronectin concentrations of diabetic and non-diabetic children with high triglycerides are not significantly different. In conclusion our data does not support the concept that plasma fibronectin is elevated in type I diabetes mellitus at least in children, but high plasma triglycerides secondary to diabetes or not is associated with higher FNp concentrations which may have implications on atherogenesis. Plasma cholesterol, apolipoproteins AI, B100 and lp(a) are not significant determinants of FNp in type I diabetic children.

The predictive value of plasma fibronectin concentration on fetal growth retardation at earlier stage of the third trimester.

In order to evaluate the predictive value of maternal plasma fibronectin (FN) concentration at 24-34 weeks on fetal intrauterine growth retardation (IUGR), a prospective double-blinded study was performed. The maternal plasma FN concentrations were measured by using a rate nephelometric procedure in the 130 initial normal nulliparous pregnant woman at 24-34 gestational weeks. The outcome of pregnancies and birth weight of their infants were followed up. IUGR was defined as that the birth weight was less than the 10th percentile for gestational age. The receiver operating characteristic curves and predictive values of FN predicting on outcome of pregnancy with IUGR were analyzed. The results showed that: (1) In a cohort of 130 initially normal nulliparous pregnant women, IUGR occurred in 14 cases during the follow-up; (2) The plasma FN levels in the women with IUGR (467.58 +/- 104.43 mg/L) were significantly higher than in the normal control group (299.44 +/- 105.55 mg/L, P < 0.01). However, there was no significant difference in the mean maternal age, gravidity, sampling gestational ages, delivering gestational ages between the two groups (P > 0.05); (3) The areas under ROC curve for predicting the outcome of pregnancy in IUGR was 0.893; (4) At the cut point of 475 mg/L FN level, the sensitivity, specificity, positive predictive value, negative predictive value and Kappa index for predicting the outcomes of pregnancy in IUGR were 57.14%, 95.69%, 61.54%, 94.87%, 0.5455 respectively. It was concluded that the maternal plasma FN might be used as an earlier predictor for screening of IUGR.

The role of fibronectin in bronchoalveolar lavage fluid of asthmatic patients.

Allergic and chronic inflammation of the airway is regarded as the main pathogenesis of bronchial asthma, in which adhesion of inflammatory cells requires the expression of adhesion molecules. Thus, to clarify the role of fibronectin (FN) in the airway inflammation of bronchial asthma, FN levels in plasma and bronchoalveolar lavage fluid (BALF) from bronchial asthmatics were determined. FN concentrations in plasma and BALF were measured by enzyme-linked immunosorvent assay (ELISA) in 17 asthmatic patients and 10 healthy controls to elucidate the role of FN in allergic inflammation. The mean FN/albumin (Alb) level in the BALF of asthmatic patients was 2.973 micrograms/mg, which was significantly higher than that of healthy controls (0.727 microgram/mg). Non-atopic asthmatics showed a significantly higher level of FN in their BALF in comparison with atopic asthmatics, although the ratio of FN to albumin showed no significant difference. FN levels in BALF correlated significantly with total cell density (r = 0.71, P < 0.05) and alveolar macrophage density (r = 0.64, P < 0.05). FN levels in plasma did not correlate with those in BALF. In conclusion, increased FN in BALF, which was produced locally in the airways of asthmatic patients, is actively involved in the regulation of allergic inflammation.

Plasma fibronectin in asthmatic patients and its relation to asthma attack.

This study investigated the relation between asthma attacks and levels of plasma fibronectin (FN) and serum eosinophilic cationic protein (ECP) in patients with bronchial asthma in order to clarify the role of FN in the airway inflammation of bronchial asthma. Plasma levels of FN were significantly higher (P < 0.025) in patients with bronchial asthma than in healthy controls. They were also significantly higher (P < 0.05) in non-atopic asthmatics than in atopic asthmatics. Furthermore, plasma FN was lower during the attack than the non-attack stage (P < 0.025), and a significant increase of plasma FN was noted (P < 0.05) in asthmatics who had more severe and more frequent attacks. Serum levels of ECP were significantly higher during the attack than the non-attack stage (P < 0.005). An increase of plasma FN in the non-attack stage after attacks showed a significant correlation (P < 0.05) with a decrease of serum ECP. These observations clearly indicate that the decrease in plasma FN associated with attacks is closely related to aggravation of airway inflammation, and that the increase in plasma FN in the non-attack stage reflects chronic airway inflammation. These results suggest that the fluctuation in plasma levels of FN may be one of the factors affecting allergic inflammation and attacks in bronchial asthma.

Effect of gestational age on plasma fibronectin concentrations in the neonate.

Fibronectin (FN) is known to have important roles in host defense against infection. The risk for neonatal sepsis increases with the degree of immaturity of the host. Conflicting results have been reported on the relationship between plasma FN levels and gestational age (GA) in the preterm neonate. In the present study, we determined plasma FN concentrations with an immunodiffusion method in 40 newborns of various gestational ages, ranging from 30 to 42 weeks. We found a strong direct correlation between plasma FN levels and GA (r = 0.86; P < 0.001). We speculate that the increased risk for neonatal sepsis with degree of prematurity may, in part, be explained by impaired defense with decreasing plasma FN levels seen with lessening GA.

Plasma fibronectin levels in ischemic heart disease

Fibronectin is a paradigm adhesive protein which has been implicated in the regulation of several cellular processes and cell-cell interactions. Large amounts of fibronectin have been detected in atherosclerotic plaques, while hypertension in animal models has been shown to rapidly increase fibronectin expression in arterial walls. The aim of the present study was to determine the levels of plasma fibronectin (FN) in 133 patients with ischemic heart disease and in 36 normal controls, and to investigate the possible association with blood pressure. Plasma FN levels in patients with ischemic heart disease were found to be significantly elevated (mean±S.D.; 46.5±14.2 mg/dl) compared with the control group (38.0±14.2 mg/dl) ( P=0.002). Plasma FN concentrations were significantly different between the hypertensive group (52.9±14.5 mg/dl) and the normal blood pressure group (41.4±11.8 mg/dl) among the patients with ischemic heart disease ( P<0.001). Plasma FN concentration was positively correlated with total cholesterol, triglyceride, systolic blood pressure and body mass index. In conclusion, the plasma fibronectin level may have pathogenetic implications in association with lipid components and blood pressure in patients with ischemic heart disease.

Hypofibronectinaemia and severity of sickle cell anaemia in Nigeria.

Plasma fibronectin levels in sickle cell anaemia and apparently healthy Nigerians were investigated to determine any correlation with disease severity. A cheaper in-house plasma fibronectin assay was also developed that could be adapted for use in Africa and elsewhere. Plasma fibronectin assay was concurrently carried out using the newly developed inhibition enzyme-linked immunosorbent assay (ELISA) and a commercial competitive binding ELISA. The in-house assay compared favourably with that of the commercial kit. The mean plasma fibronectin levels in sickle cell anaemia subjects were significantly lower than that of control subjects (P < 0.001). Plasma fibronectin concentration could therefore be useful in assessing the severity of sickle cell anaemia.

Hypofibronectinaemia and severity of sickle cell anaemia in Nigeria

Plasma fibronectin levels in sickle cell anaemia and apparently healthy Nigerians were investigated to determine any correlation with disease severity. A cheaper in‐house plasma fibronectin assay was also developed that could be adapted for use in Africa and elsewhere. Plasma fibronectin assay was concurrently carried out using the newly developed inhibition enzyme‐linked immunosorbent assay (ELISA) and a commercial competitive binding ELISA. The in‐house assay compared favourably with that of the commercial kit. The mean plasma fibronectin levels in sickle cell anaemia subjects were significantly lower than that of control subjects (P &lt; 0·001). Plasma fibronectin concentration could therefore be useful in assessing the severity of sickle cell anaemia.

Flow-Mediated Vasodilation and Plasma Fibronectin Levels in Preeclampsia

To clarify the vascular endothelial function in pregnant women with hypertensive disorders, we assessed the flow-mediated vasodilation in the radial artery and compared it with plasma fibronectin levels. We determined flow-mediated vasodilation by measuring the change in radial artery diameter during hyperemia in 58 normal pregnant women, 22 preeclamptic pregnant women, and 15 pregnant women with chronic hypertension. In 41 of the 95 pregnant women, we measured the plasma fibronectin levels. Flow-mediated vasodilation in preeclamptic women was significantly less than that in normal pregnant women (P:<0.001). In chronic hypertensive women, flow-mediated vasodilation was significantly less than that in normal pregnant women (P:<0.001) but more than that in preeclamptic women (P:<0.001). Flow-mediated vasodilation showed significant negative correlation with plasma fibronectin levels (P:<0.001, r=0.73). Our results indicate that the endothelial function can be noninvasively assessed in pregnant women with hypertensive disorders by measuring the flow-mediated vasodilation of the radial artery with high-resolution ultrasound.

Decreased plasma levels of fibronectin in amyotrophic lateral sclerosis.

Fibronectin (FN) possesses a wide range of biological functions. However, the role of plasma FN in vivo has not yet been established and there have been no published studies of plasma FN in ALS. The aim of this study was to measure plasma FN in ALS patients. We measured plasma FN levels in 28 ALS patients, 18 control subjects with other neurologic or muscular diseases (control group A) and 21 healthy adults (control group B). The age and sex distributions among the 3 groups were comparable. Plasma FN levels were significantly lower in ALS patients than in control groups A and B. There was also a significant negative correlation between plasma FN levels and duration of illness in ALS patients. These data suggest that a metabolic alteration of FN may take place in ALS and that the measurement of plasma FN may serve as an indicator of clinical progression of this disorder.

Correlation between placental bed biopsy findings, vascular cell adhesion molecule and fibronectin levels in pre-eclampsia.

To determine the correlation between placental bed biopsy findings, and blood levels of the vascular cell adhesion molecule (VCAM-1) and fibronectin in pre-eclampsia/eclampsia, and to evaluate the relationship between these variables and severity of the disease. A prospective case-control study. Department of Obstetrics and Gynaecology, Cerrahpasa Medical Faculty, Istanbul. Thirty-five women with pre-eclampsia/eclampsia were compared with 25 healthy women with uncomplicated pregnancies. Twenty-one placental bed biopsies from pre-eclamptic pregnancies were compared with 17 from normal pregnancies. Peripheral venous blood levels of VCAM-1 and fibronectin, measured by enzyme-linked immunoassay and radial immune diffusion technique. In pre-eclampsia/eclampsia, blood VCAM-1 and fibronectin levels were higher than in normal pregnancy. Levels of both fibronectin and VCAM-1 correlated significantly with the diastolic blood pressure (r = 0.49 and r = 0.65, P < 0.001). There was also a significant direct linear correlation between plasma fibronectin and VCAM-1 levels (r = 0.57, P < 0.001). Normotensive women all had normal placental bed biopsy findings and the incidence of pathological placental bed biopsy findings increased with the severity of the pre-eclampsia. Inadequate trophoblastic invasion of spiral arteries, and elevated levels VCAM-1 and fibronectin were found in women with pre-eclampsia. The magnitude of defective trophoblastic invasion, and blood levels of VCAM-1 and fibronectin correlate with the clinical severity of pre-eclampsia.

Serial plasma fibronectin levels in pre-eclamptic and normotensive women

Objective: Endothelial cell damage has been put forward as an underlying factor for development of pre-eclampsia. This study was carried out to see if fibronectin, which is a marker of endothelial damage, could be used as a marker of pre-eclampsia. Methods: A longitudinal study was conducted on 100 normotensive primigravidae registered before 20 weeks of gestation. These subjects were followed until delivery and three blood samples were collected, first at registration, i.e. before 20 weeks, second around 28 weeks and third at 36 weeks or later till delivery. Fibronectin levels were assayed by ELISA and women observed for any signs of pre-eclampsia. Results: Fourteen subjects developed pre-eclampsia. Fibronectin levels were observed to rise as pregnancy advanced but the rise was significantly higher in subjects who developed pre-eclampsia. The fibronectin levels were also significantly higher in these 14 subjects even in the first sample, i.e. before 20 weeks of gestation when compared with normotensive subjects ( P<0.01). Conclusions: Fibronectin levels could be used as an early valuable biomarker for the development of pre-eclampsia.

Efficacy of exogenous fibronectin in wound healing in malnourished rats

Background/Purpose: Fibronectin (FN) plays an important role in fibrin matrix formation during the wound healing process. The authors investigated whether exogenous FN increases the bursting strength (BS) of surgical wounds in malnourished rats. Methods: Ninety rats were grouped according to three nutritional conditions (n = 30 in each group). All animals underwent a transverse celiotomy after 3 weeks of feeding, and FN (2 mg/body/day) was given postoperatively to 15 rats in each of the three groups. Wound BS was measured on postoperative days (PODs) 3, 5, and 7 after removal of the sutures. Results: BS in normally nourished rats (group N; 142.6 ± 23.4 mmHg) was significantly higher than that in protein malnourished rats (group PM, 110.2 ± 11.2 mm Hg) and protein/calorie (Cal)-malnourished rats (group PCM, 76.5 ± 10.7 mm Hg) on POD 7 ( P < .01). However, BS values for groups PM + FN (147.0 ± 21.1 mmHg) and PCM + FN (115.1 ± 28.9 mm Hg) were intensified significantly in comparison with groups PM and PCM ( P < .01). Plasma FN levels in rats of the three FN nontreated groups were similarly decreased on POD 3 or 5, but returned to the preoperative level on POD 7, whereas those for the other three FN-treated groups increased after POD 3. Conclusion: Intravenous administration of FN might strengthen the weakened wounds of malnourished animals.

Enhancement of fibronectin expression in rat lung by ozone and an inflammatory stimulus.

This study investigated the relationship of fibronectin expression and induction of pulmonary inflammation by ozone (O3). Rats were exposed to 0.8 parts/million O3 to induce lung inflammation. A second inflammatory stimulus, rabbit serum, was applied intratracheally to augment O3-induced inflammation. Bronchoalveolar lavage fluid (BALF) and lung tissues were analyzed for fibronectin protein and mRNA expression. Blood plasma was analyzed to investigate the potential of a minimally invasive procedure in predicting lung inflammation and fibronectin levels. Significant increases in the levels of fibronectin protein in the BALF and lung tissue after O3 exposure were further enhanced by pretreatment with normal serum. An increase in fibronectin mRNA following O3 exposure was also enhanced by serum pretreatment, which by itself had no effect on lung fibronectin mRNA expression. Plasma fibronectin levels were comparable in air-PBS and O3-PBS groups but increased in the O3-serum group. The results suggest leakage of fibronectin from blood plasma into the lung following intratracheal application of rabbit serum and upregulation of local synthesis following O3 exposure.