Plasma Fibronectin Levels 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

Impact of Antidepressant Treatment on Fibronectin Levels in Patients with Depression and Chronic Heart Failure

IntroductionInflammation has emerged as a critical factor in the pathophysiology of both depression and chronic heart failure (HF). Chronic heart failure, a complex clinical syndrome, is often accompanied by a state of heightened inflammation, with elevated levels of proinflammatory markers. Likewise, depression, a prevalent comorbidity in HF patients, has been intricately linked to inflammation, with evidence suggesting a bidirectional relationship.ObjectivesThis study aimed to evaluate the effect of antidepressant treatment on plasma fibronectin levels in patients with comorbid depression and chronic heart failure.MethodsWe enrolled a total of 113 patients with HF, all of whom had comorbid depression. The patients were divided into two groups based on the antidepressant treatment they received: Group 1 (n = 78) received vortioxetine, and Group 2 (n = 35) received sertraline. Before initiating treatment and after 6 months, we measured fibronectin levels in the patients’ plasma.ResultsThe study revealed a significant difference in the effects of the two antidepressants on fibronectin levels. Patients treated with vortioxetine demonstrated a substantial reduction in fibronectin levels post-treatment, with an approximate threefold decrease compared to the pre-treatment levels (pre-treatment value ± standard deviation) μg/ml to (post-treatment value ± standard deviation) μg/ml, (p<0.05). Conversely, patients treated with sertraline experienced a comparatively lesser reduction in fibronectin levels, with a change from (pre-treatment value ± standard deviation) μg/ml to (post-treatment value ± standard deviation) μg/ml (p<0.05).ConclusionsThis study highlights the considerable impact of vortioxetine on fibronectin levels in patients with comorbid depression and chronic heart failure, resulting in a significant reduction. In contrast, sertraline’s effect on fibronectin levels, while present, is notably less pronounced. The study emphasizes the potential therapeutic benefit of vortioxetine in cardiac remodeling associated with depression in patients with chronic heart failure, underscoring the need for further research and exploration.Disclosure of InterestNone Declared

Plasma Fibronectin as a Novel Predictor of Coronary Heart Disease: A Retrospective Study.

Although fibronectin has been associated with the pathogenesis of atherosclerosis, little is currently known about the relationship between plasma fibronectin and coronary heart disease (CHD). This retrospective study aimed to determine the predictive value of plasma fibronectin for CHD and its severity. A total of 1644 consecutive patients who underwent selective coronary angiography were recruited into the present study. The characteristics and results of the clinical examination of all patients were collected. Logistic regression analyses were performed to determine the predictive value of plasma fibronectin for the presence and severity of CHD. Compared with non-CHD patients, the CHD patients showed significantly higher plasma levels of troponin I and creatine kinase isoenzyme, along with lower plasma levels of fibronectin. However, no significant differences were detected in plasma fibronectin among patients with different grades of CHD. The logistic regression model showed that plasma fibronectin remained an independent predictor of CHD after adjustment with a 1.39-fold increased risk for every 1 SD decrease in plasma fibronectin. Nevertheless, plasma fibronectin could not predict the severity of CHD determined by the number of stenosed vessels and the modified Gensini score. This study demonstrated that lower plasma fibronectin might be an independent predictor of CHD, but it may be of no value in predicting the severity of CHD.

Over-expression of Dyrk1A affects bleeding by modulating plasma fibronectin and fibrinogen level in mice.

Down syndrome is the most common chromosomal abnormality in humans. Patients with Down syndrome have hematologic disorders, including mild to moderate thrombocytopenia. In case of Down syndrome, thrombocytopenia is not associated with bleeding, and it remains poorly characterized regarding molecular mechanisms. We investigated the effects of overexpression of Dyrk1A, an important factor contributing to some major Down syndrome phenotypes, on platelet number and bleeding in mice. Mice overexpressing Dyrk1A have a decrease in platelet number by 20%. However, bleeding time was found to be reduced by 50%. The thrombocytopenia and the decreased bleeding time observed were not associated to an abnormal platelet receptors expression, to a defect of platelet activation by ADP, thrombin or convulxin, to the presence of activated platelets in the circulation or to an abnormal half-life of the platelets. To propose molecular mechanisms explaining this discrepancy, we performed a network analysis of Dyrk1A interactome and demonstrated that Dyrk1A, fibronectin and fibrinogen interact indirectly through two distinct clusters of proteins. Moreover, in mice overexpressing Dyrk1A, increased plasma fibronectin and fibrinogen levels were found, linked to an increase of the hepatic fibrinogen production. Our results indicate that overexpression of Dyrk1A in mice induces decreased bleeding consistent with increased plasma fibronectin and fibrinogen levels, revealing a new role of Dyrk1A depending on its indirect interaction with these two proteins.

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.

Genomic Analysis of Vascular Invasion in HCC Reveals Molecular Drivers and Predictive Biomarkers.

Vascular invasion (VI) is a critical risk factor for HCC recurrence and poor survival. The molecular drivers of vascular invasion in HCC are open for investigation. Deciphering the molecular landscape of invasive HCC will help identify therapeutic targets and noninvasive biomarkers. To this end, we undertook this study to evaluate the genomic, transcriptomic, and proteomic profile of tumors with VI using the multiplatform cancer genome atlas (The Cancer Genome Atlas; TCGA) data (n=373). In the TCGA Liver Hepatocellular Carcinoma cohort, macrovascular invasion was present in 5% (n=17) of tumors and microvascular invasion in 25% (n=94) of tumors. Functional pathway analysis revealed that the MYC oncogene was a common upstream regulator of the mRNA, miRNA, and proteomic changes in VI. We performed comparative proteomic analyses of invasive human HCC and MYC-driven murine HCC and identified fibronectin to be a proteomic biomarker of invasive HCC (mouse fibronectin 1 [Fn1], P=1.7×10-11 ; human FN1, P=1.5×10-4 ) conserved across the two species. Mechanistically, we show that FN1 promotes the migratory and invasive phenotype of HCC cancer cells. We demonstrate tissue overexpression of fibronectin in human HCC using a large independent cohort of human HCC tissue microarray (n=153; P<0.001). Lastly, we showed that plasma fibronectin levels were significantly elevated in patients with HCC (n=35; mean=307.7 μg/mL; SEM = 35.9) when compared to cirrhosis (n=10; mean=41.8 μg/mL; SEM = 13.3; P<0.0001). Our study evaluates the molecular landscape of tumors with VI, identifying distinct transcriptional, epigenetic, and proteomic changes driven by the MYC oncogene. We show that MYC up-regulates fibronectin expression, which promotes HCC invasiveness. In addition, we identify fibronectin to be a promising noninvasive proteomic biomarker of VI in HCC.

Aging-induced isoDGR-modified fibronectin activates monocytic and endothelial cells to promote atherosclerosis

Background and aimsAging is the primary risk factor for cardiovascular disease (CVD), but the mechanisms underlying age-linked atherosclerosis remain unclear. We previously observed that long-lived vascular matrix proteins can acquire ‘gain-of-function’ isoDGR motifs that might play a role in atherosclerotic pathology. MethodsIsoDGR-specific mAb were generated and used for ELISA-based measurement of motif levels in plasma samples from patients with coronary artery diseases (CAD) and non-CAD controls. Functional consequences of isoDGR accumulation in age-damaged fibronectin were determined by bioassay for capacity to activate monocytes, macrophages, and endothelial cells (signalling activity, pro-inflammatory cytokine expression, and recruitment/adhesion potential). Mice deficient in the isoDGR repair enzyme PCMT1 were used to assess motif distribution and macrophage localisation in vivo. ResultsIsoDGR-modified fibronectin and fibrinogen levels in patient plasma were significantly enhanced in CAD and further associated with smoking status. Functional assays demonstrated that isoDGR-modified fibronectin activated both monocytes and macrophages via integrin receptor ‘outside in’ signalling, triggering an ERK:AP-1 cascade and expression of pro-inflammatory cytokines MCP-1 and TNFα to drive additional recruitment of circulating leukocytes. IsoDGR-modified fibronectin also induced endothelial cell expression of integrin β1 to further enhance cellular adhesion and matrix deposition. Analysis of murine aortic tissues confirmed accumulation of isoDGR-modified proteins co-localised with CD68+ macrophages in vivo. ConclusionsAge-damaged fibronectin features isoDGR motifs that increase binding to integrins on the surface of monocytes, macrophages, and endothelial cells. Subsequent activation of ‘outside-in’ signalling elicits a range of potent cytokines and chemokines that drive additional leukocyte recruitment to the developing atherosclerotic matrix.

Assessment of plasma and tissue fibronectin EIIIB splice variant expressions measured serially using RT-PCR in a wound model of rabbits.

Fibronectin (FN) is an indispensable part of the extracellular matrix. During regeneration or wound healing, the plasma form of FN is incorporated into the fibrin clots to form a temporary fibrin-FN matrix, and also locally synthesized cellular FN migrates to the clot to regenerate the injured tissue. We aimed to examine wound tissue FN EIIIB and plasma FN EIIIB expression levels in an experimental wound healing model in rabbits. Plasma and tissue EIIIB splice variant expressions were measured serially with RT-qPCR in a cutaneous wound model of rabbits. Tissue FN expression increased as beginning on day 3 and continued to increase on days 6 and 9, reaching maximum expression at day 12 before starting to decrease. On the contrary to the tissue levels, plasma FN levels gradually decreased until day 15 when expression returned to the initial values. The findings of the current study support that tissue EIIIB expression level increases during wound healing; and plasma EIIIB expression level decreases minimal changed. This is in contrast to reports where plasma FN provisionally helps ECM formation. Therefore, our data show an essential role of EIIIB at the tissue level in accelerating the wound healing process. The RT-qPCR method in our experimental setup can provide more accurate and precise results compared to the antibody-based methods.

Plasma Fibronectin Levels Identified via Quantitative Proteomics Profiling Predicts Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B.

Seroclearance of hepatitis B surface antigen (HBsAg) is a potentially achievable target of chronic hepatitis B (CHB). Plasma proteins relevant to HBsAg seroclearance remain undetermined. We prospectively recruited treatment-naive CHB patients with spontaneous HBsAg seroclearance and matched HBsAg-positive controls. Plasma protein profiling was performed using isobaric tags for relative and absolute quantitation-based proteomics, with the expression of candidate proteins validated in a separate cohort. The predictive value of fibronectin was assessed at 3 years, 1 year (Year -1) before, and at the time (Year 0) of HBsAg seroclearance. Four hundred eighty-seven plasma proteins were identified via proteomics, with 97 proteins showing altered expression. In the verification cohort (n = 90), median plasma fibronectin levels in patients with HBsAg seroclearance was higher than in controls (P = .009). In the longitudinal cohort (n = 164), patients with HBsAg seroclearance, compared with controls, had a higher median fibronectin levels at Year -1 (413.26 vs 227.95 µg/mL) and Year 0 (349.45 vs 208.72 µg/mL) (both P < .001). In patients with an annual HBsAg log reduction >0.5, Year -1 fibronectin level achieved an area under the receiving operator characteristic of 0.884 in predicting HBsAg seroclearance. Using proteomics-based technology, plasma fibronectin may be associated with HBsAg seroclearance and a potential predictor of "functional cure".

Fibronectin modulates formation of PF4/heparin complexes and is a potential factor for reducing risk of developing HIT

AbstractHeparin-induced thrombocytopenia (HIT) is caused by platelet-activating anti–platelet factor 4 (PF4)/heparin antibodies. Platelet activation assays that use “washed” platelets are more sensitive for detecting HIT antibodies than platelet-rich plasma (PRP)–based assays. Moreover, heparin-exposed patients vary considerably with respect to the risk of PF4/heparin immunization and, among antibody-positive patients, the risk of subsequent “breakthrough” of clinical HIT with manifestation of thrombocytopenia. We used washed platelets and PRP, standard laboratory HIT tests, and physicochemical methods to identify a plasma factor interfering with PF4/heparin complexes and anti-PF4/heparin antibody–platelet interaction, thus explaining differences in functional assays. To investigate a modulating risk for PF4/heparin immunization and breakthrough of HIT, we also tested 89 plasmas from 2 serosurveillance trials. Fibronectin levels were measured in 4 patient groups exhibiting different degrees of heparin-dependent immunization and expression of HIT. The heat-labile plasma protein, fibronectin, inhibited PF4 binding to platelets in a dose-dependent fashion, particularly in washed (vs PRP) systems. Fibronectin also inhibited PF4/heparin binding to platelets, anti-PF4/heparin antibody binding to PF4/heparin complexes, and anti-PF4/heparin antibody–induced platelet activation as a result of PF4/heparin complex disruption. In addition, plasma fibronectin levels increased progressively among the following 4 patient groups: enzyme-linked immunosorbent assay (ELISA)+/serotonin-release assay (SRA)+/HIT+ < ELISA+/SRA+/HIT− ∼ ELISA+/SRA−/HIT− < ELISA−/SRA−/HIT−. Altogether, these findings suggest that fibronectin interferes with PF4/heparin complex formation and anti-PF4/heparin antibody–induced platelet activation. Reduced fibronectin levels in washed platelet assays help to explain the greater sensitivity of washed platelet (vs PRP) assays for HIT. More importantly, lower plasma fibronectin levels could represent a risk factor for PF4/heparin immunization and clinical breakthrough of HIT.

Whole Exome Sequencing of HIV-1 long-term non-progressors identifies rare variants in genes encoding innate immune sensors and signaling molecules

Common CCR5-∆32 and HLA alleles only explain a minority of the HIV long-term non-progressor (LTNP) and elite controller (EC) phenotypes. To identify rare genetic variants contributing to the slow disease progression phenotypes, we performed whole exome sequencing (WES) on seven LTNPs and four ECs. HLA and CCR5 allele status, total HIV DNA reservoir size, as well as variant-related functional differences between the ECs, LTNPs, and eleven age- and gender-matched HIV-infected non-controllers on antiretroviral therapy (NCARTs) were investigated. Several rare variants were identified in genes involved in innate immune sensing, CD4-dependent infectivity, HIV trafficking, and HIV transcription mainly within the LTNP group. ECs and LTNPs had a significantly lower HIV reservoir compared to NCARTs. Furthermore, three LTNPs with variants affecting HIV nuclear import showed integrated HIV DNA levels below detection limit after in vitro infection. HIV slow progressors with variants in the TLR and NOD2 pathways showed reduced pro-inflammatory responses compared to matched controls. Low-range plasma levels of fibronectin was observed in a LTNP harboring two FN1 variants. Taken together, this study identified rare variants in LTNPs as well as in one EC, which may contribute to understanding of HIV pathogenesis and these slow progressor phenotypes, especially in individuals without protecting CCR5-∆32 and HLA alleles.

Fibronectin gene polymorphisms in HCV related type II mixed cryoglobulinemia: risk of development of B-cell lymphoma

B-cell non-Hodgkin lymphoma (B-NHL) are clonal malignancies with diverse clinical presentations, pathogenesis, and biologic behavior. Hepatitis C virus (HCV) is a major leading cause of liver-related morbidity and B-cell lymphoproliferative diseases such as mixed cryoglobulinemic syndrome (MCns) and B-NHL. Fibronectin (FN) is a multifunctional glycoprotein of 250 kDa which is encoded on a gene that is 75 kb in length, located on chromosome 2q34–36 and consists of 50 exons. Polymorphisms of the fibronectin gene are as follows: HindIII, HaeIII, TaqI, and MspI. The aim of the current study was to investigate the possible link between the two FN polymorphisms (called MspI “CC genotype, CD genotype and DD genotype” and HaeIII “AA genotype, AB genotype and BB genotype”) and the development of lymphoma in HCV-positive patients with mixed cryoglobulinemic syndrome compared to healthy age- and sex-matched individuals. The present study included 75 patients; 25 HCV-positive patients with MCns and 50 B-NHL patients, in addition to 25 healthy controls. To achieve this aim, genotyping for FN gene was done by PCR-RFLP technique and screening for HCV infection was performed by ELISA and confirmed by RT-PCR, cryoglobulins have been detected by cold precipitation (4 °C for 72–96 h) and plasma FN levels have been assessed by ELISA. The study revealed that HaeIII-AB genotype can be considered as a risk factor for NHL development and high HaeIII-A allele frequency seems to be associated with NHL development. We did not find any significant difference between all patients’ groups and controls regarding MspI genotyping. It was also found that plasma FN level did not show any significant difference between B-NHL patients and each of HCV positive patients with MCns and controls. Our study provides further evidence for the role of HaeIII-AB FN gene polymorphism as a risk factor for B-NHL development in sub-population of Egyptian HCV-positive patients with MCns. We also found that HaeIII-A allele has been significantly increased in overall B-NHL patients.

Thyroid hormone regulates fibronectin expression through the activation of the hypoxia inducible factor 1

Thyroid hormones regulate gene expression via both canonical and non-canonical signaling. Hyperthyroidism is associated with elevated plasma levels of fibronectin (FN): in this study we elucidate the molecular mechanism through which triiodothyronine (T3) regulates FN and demonstrate that T3 induces FN expression via a non-canonical pathway by activating hypoxia-inducible factor-1 (HIF-1). We found that T3 treatment increased cellular and secreted FN in human hepatoma cells (HepG2) and human dermal fibroblasts (HF) via the PI3K/Akt/HIF-1 pathway. The inhibition of either Akt phosphorylation with wortmannin or HIF-1 with YC1 in both cell types prevented HIF-1α synthesis and FN positive regulation upon T3 treatment. We showed that HIF-1α overexpression per se was sufficient to up-regulate FN in both cell lines as demonstrated by the transient transfection of both the constitutively active and wild-type forms of HIF-1α. Our data demonstrate the involvement of the PI3K/Akt/HIF-1 pathway in mediating T3 induced FN up-regulation.

Effects of Quercetin on Cardiac Fibrosis in Patients with Acute Myocardial Infarction and Arterial Hypertension

Arterial hypertension is an independent predictor of acute myocardial infarction. Nowadays, plasma levels of fibronectin and matrix metalloproteinase 9 are the markers of left ventricular remodeling.The objective of the research was to investigate potential antifibrotic effects of Quercetin in patients with acute myocardial infarction and arterial hypertension.Material and methods. 130 patients with myocardial infarction (63 individuals with concomitant arterial hypertension and 67 individuals without it) were observed. All the patients were divided into groups of basic treatment and additional prescription of Quercetin. Transthoracic echocardiogram was used. To evaluate plasma level of fibronectin and matrix metalloproteinase 9 the ELISA method was applied.Results. In all the patients, a significant decrease in fibronectin plasma levels was observed since the 28th day of treatment; however, it was more significant in group of additional prescription of Quercetin. Revascularization and pharmacological management of myocardial infarction resulted in the reduction in matrix metalloproteinase 9 plasma levels in all the patients since the 7th day of treatment; however, it was more significant in group of additional prescription of Quercetin. Conclusions. Quercetin possesses potential antifibrotic properties causing a reduction in plasma levels of fibronectin and matrix metalloproteinase 9 in patients with myocardial infarction and concomitant arterial hypertension.

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.

Correlation between plasma fibronectin level and renal function in pregnant women with Preeclampsia.

Correlation between plasma fibronectin level and renal function in pregnant women with Preeclampsia.

Utility of a single mid-trimester measurement of plasminogen activator Type 1 and fibronectin to predict preeclampsia in pregnancy

Background:Preeclampsia (PE) is the second most common cause of maternal death after obstetric hemorrhage in Africa, a resource-limited region. This study was designed to examine the potential usefulness of a single screening plasma plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) level for the prediction of PE in pregnant women.Materials and Methods:In a cohort of 180 pregnant women who were normotensive at baseline, venous blood samples were obtained before 20 weeks of gestation for the assay of plasma levels of PAI-1 and FN levels measured by enzyme-linked immunoassay technique. Twenty nonpregnant normotensive women were also evaluated as a control group. Outcomes of gestation were evaluated and correlated with the plasma levels of PAI and FN measured at mid-trimester. Mean plasma values of PAI-1 and FN were also compared between the different outcome groups.Results:Plasma PAI-1 level was significantly higher in the pregnant women (8.68 ± 0.56 ng/ml) than in nonpregnant controls (5.55 ± 0.32 ng/ml) (P = 0.01). However, plasma FN did not show any significant difference in pregnant women (2.60 ± 0.37 μg/ml) and nonpregnant controls (2.60 ± 0.23 μg/ml) (P = 0.9). Mid-trimester mean plasma PAI-1 level measured in women who developed PE (7.08 ± 5.49 ng/ml, n = 12) and gestational hypertension (GH) (9.78 ± 6.2 ng/ml, n = 13) was not significantly different in comparison to normotensive pregnant women (8.78 ± 5.63 ng/ml, n = 153) (P = 0.75). Likewise, the mean FN level in women who developed PE was also not significantly different from nonpreeclamptics; however, the FN level in the pregnant women who developed GH was significantly different from women who remained normotensive throughout pregnancy (P = 0.02).Conclusion:Single mid-trimester assessment of PAI-1 and FN levels in maternal plasma was not found to be useful in predicting PE as an outcome of pregnancy in the study population.

The effect of ivabradine and ω-3 polyunsaturated fatty acids on the fibronectin plasma levels in patients with heart failure

Chronic heart failure (HF) is a highly prevalent chronic pathological condition with high morbidity and mortality rates. The cost for HF treatment is 2% of the national health expenditures each year. Fibronectin (Fn) has a crucial role in the process of tissue-specific morphogenesis and cell differentiation in embryogenesis; it stimulates fibroblasts and different growth factors during wound healing and tissue reparation. The aim of our study was to assess the possible effects of Ivabradine and ω-3 polyunsaturated fatty acids on the fibronectin plasma level in patients with heart failure. 357 Patients with ischemic HF and the sinus rhythm were observed. In accordance to treatment regimens all patients were divided into four groups: group I – basic treatment; group II – basic treatment and Ivabradine; group III – basic treatment and PUFA; group IV – basic treatment with Ivabradine and PUFA. The fibronectin levels were measured by ELISA method. The average value of the Fn concentration in HF patients was 1.25 times higher than in the control group (p&lt;0.05). In patients with basic HF treatment the tendency to the Fn plasma level decrease (p&gt;0.05) was observed. In the group with additional prescription of Ivabradine the concentration of this protein in the blood decreased by 14.5% (p&lt;0.01). The same situation was observed in the group with additional use of PUFA – by 11.1% (p&lt;0.05). In group IV the plasma concentration of Fn decreased by 12.9% (p&lt;0.05). Thus, Ivabradine and ω-3 polyunsaturated fatty acids, either alone or in combination, decrease the plasma levels of fibronectin in patients with heart failure, and it shows a pronounced cardioprotective effect.

Association of plasma fibronectin level with left atrial electrical and structural remodelling in lone paroxysmal atrial fibrillation: a cross-sectional study

Atrial fibrosis is one of the main components of atrial fibrillation (AF) pathophysiology and culminates in structural, electrical and contractile remodelling. Fibronectin is one of the well-known mediators of fibrogenesis. However, the association of plasma fibronectin with atrial remodelling has not been studied previously. Therefore, the aim of this study was to assess the relationship between plasma fibronectin level and atrial electrical and structural remodelling in patients with lone paroxysmal AF. A total of 51 lone paroxysmal AF patients and 40 age-, gender- and body mass index-matched healthy control subjects were enrolled. Plasma levels of fibronectin and high sensitive C-reactive protein (hs-CRP) were measured and transthoracic echocardiography for assessment of total atrial conduction time (TACT) and left atrial (LA) volume index was performed on all study participants. Plasma fibronectin, hs-CRP, TACT, LA diameter and LA volume index were significantly higher in lone paroxysmal AF group compared to healthy controls (p<0.05). Also, there was a positive correlation between plasma fibronectin level and TACT (r=0.362, p<0.001) and LA volume index (r=0.371, p<0.001). In multivariate logistic regression analysis, age, plasma fibronectin level (Odds ratio - OR: 1.003, 95% CI: 1.001-1.005, p=0.026) and hs-CRP (OR: 2.312, 95% CI: 1.503-6.459, p=0.017) were found to be the predictors of LA structural remodelling; however, only plasma fibronectin level (OR: 1.003, 95% CI: 1.001-1.005, p=0.032) and hs-CRP (OR: 3.212, 95% CI: 1.214-5.752, p=0.033) were found as the predictors of LA electrical remodelling. Our study results showed that profibrotic and proinflammatory biomarkers were associated with left atrial structural and electrical remodelling in lone paroxysmal AF patients.

Maternal soluble vascular cytoplasmic adhesion molecule-1 and fibronectin levels in early- and late-onset preeclamptic pregnancies

Objective: The purpose of this study was to investigate maternal plasma soluble vascular cytoplasmic adhesion molecule-1 (sVCAM- 1) and fibronectin levels in the patients with early-onset preeclampsia (EOP) and late-onset preeclampsia (LOP) and also to determine whether different mechanisms are involved in these two forms of disorders. Material and Methods: The authors performed a case control study consisting of randomly selected 80 healthy pregnant women (group 1= control group) and 80 preeclamptic women (group 2= defined study group). Study group consisted of 43 patients with EOP and 37 patients with LOP. sVCAM-1 and fibronectin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) and the findings were compared between the groups. Results: The mean levels of sVCAM-1 and fibronectin were significantly higher in the LOP group than those in the normotensive group (p = 0.043 and 0.010 respectively). Markers were significantly different between the two hypertensive groups of pregnancy. The EOP group had a higher level of sVCAM-1 and fibronectin concentration than the LOP group (p = 0.01, for both markers). There was a positive correlation both between the values of plasma fibronectin and the systolic- diastolic blood pressure measurements (r:0.43 and 0.44, respectively), and between sVCAM-1 and the systolic/diastolic blood pressure measurements (r = 0.54 and 0.64, respectively). Conclusion: Increased plasma levels of fibronectin and sVCAM-1 were found in the preeclamptic patients, especially in those with early-onset preeclampsia. These markers might be related to the pathogenesis of different types of preeclampsia.