Serum tenascin-C Levels Research Articles

The Role of Tenascin-C in the Physiopathology of Familial Mediterranean Fever.

Familial Mediterranean fever (FMF) is an autoinflammatory disease common in the Mediterranean basin. It has been determined that tenascin-C level is increased in rheumatic inflammatory diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus, and systemic sclerosis. However, the role of tenascin-C has not been investigated in FMF. This study aimed to investigate serum tenascin-C levels in FMF patients and to investigate possible relationships between them. About 38 patients diagnosed with FMF and 40 healthy controls were included in the study. The patient's sex, age, clinical symptoms, physical examination, and laboratory results were recorded. Serum tenascin-C levels were determined by the enzyme-linked immunosorbent assay (ELISA) method. The serum tenascin-C levels were significantly lower in the FMF patients (10297 ± 8107 pg/ml) compared to the healthy control group (29461 ± 13252 pg/ml) (p < 0.001). In receiver operating characteristic(ROC) analysis, when the cut-off point was chosen as 11076 pg/ml, sensitivity was 77.1%and specificity was 91.9%. When the cut-off point was chosen as 19974 pg/ml, sensitivity was 91.4%and specificity was 75.7%. It was determined that the serum tenascin-C levels did not correlate with age, gender, and laboratory parameters in the healthy control group and FMF patients (p > 0.05). This is the first study investigating tenascin-C levels in FMF. Tenascin-C levels in FMF patients were lower than in healthy controls. Low tenascin-C levels in FMF, which are high in other chronic rheumatic diseases, may be a valuable indicator. Therefore, serum tenascin-C level seems to be a useful marker in distinguishing FMF patients from healthy individuals.

Beyond the matrix: exploring tenascin-c (TNC) as a crucial player in diabetic cardiovascular dysfunction

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Burgermeister Found Wien-Project number : 21001 Introduction Diabetic cardiomyopathy (CMP) is a complex manifestation of diabetes-linked cardiac and vascular dysfunction, but the molecular pathogenesis is still largely unknown. Notably the expression of Tenascin-C (TNC), an extracellular matrix glycoprotein, contributes to the development of cardiovascular diseases and diabetic patients have elevated serum TNC levels. However, the role and mechanism of TNC to diabetic CMP progression remains elusive. Purpose Here, we longitudinally evaluated functional and molecular role of TNC in CMP-induced cardiovascular dysfunction in a murine model. In addition, we used RNA sequencing with cardiac tissues from non-diabetic and diabetic wild type (wt) and TNC KO mice for further investigation. Methods Diabetes was induced in adult male mice, wt (AJ) and TNC-KO strains, by repeated Streptozotocin (STZ) injections (50 mg/kg). Echocardiography, myography, hemodynamics, histology, molecular and cellular analyses were performed to assess the role of TNC in diabetes-associated CV complications. Additionally, RNA-sequencing was analyzed in left ventricular (LV) tissue samples from diabetic and non-diabetic wt and TNC-KO mice providing further molecular insights. Results TNC KO mice showed preserved LV ejection fraction, and endothelium-dependent relaxation (p&amp;lt;0.05 and p&amp;lt;0.001, respectively), reduced cardiac fibrosis and distinctive coronary vessel characteristics, implying enhanced LV perfusion. In addition, the plasma levels of oxidative stress marker malondialdehyde was significantly alleviated in TNC KO diabetic mice in comparison to diabetic wt mice. Cardiomyocytes from diabetic wt mice exhibited stiffness (Fpassive and Factive), which was corrected to control level in cardiomyocytes from TNC KO diabetic hearts. Further, ex vivo isolated heart experiments demonstrated that the administration of recombinant human TNC (80 ng/ml) resulted in a significant reduction in LV hemodynamics (p&amp;lt;0.01) and myocardial energetics (ATP levels, p&amp;lt;0.01). Analysis of RNA sequencing data demonstrated that decreased expression of matrix remodeling genes Serpin1 and Ccn1 links to alleviation of fibrosis in TNC KO diabetic heart. Furthermore, Gene Ontology (GO) enrichment analysis shed light on mitochondrial changes in diabetic hearts. Our pathway analysis also identified that Hsp90aa1 as a crucial gene associated with preprotein import into the mitochondrial membrane, may suggest potential mitochondrial dysfunction in diabetic hearts. Conclusion In conclusion, lack of TNC improved long-term cardiac function in diabetes by reducing cardiac fibrosis, vascular dysfunction, oxidative stress and cardiac energetics. Thus, inhibition of TNC may prevent the diabetic heart from extensive fibrosis and energetics dysfunction that accelerates the development of HF, providing a potential targeted therapy.

The serum tenascin C level is a marker of metabolic disorder-related inflammation affecting pancreatic cancer prognosis

Obesity is a risk factor for pancreatic cancer development, partly due to the tissue environment of metabolic disorder-related inflammation. We aimed to detect a tissue environment marker triggered by obesity-related metabolic disorders related to pancreatic cancer progression. In murine experiments, Bl6/j mice fed a normal diet (ND) or a high-fat diet (HFD) were orthotopically injected with mPKC1, a murine-derived pancreatic cancer cell line. We used stocked sera from 140 pancreatic cancer patients for analysis and 14 colon polyp patients as a disease control. Compared with ND-fed mice, HFD-fed mice exhibited obesity, larger tumors, and worse prognoses. RNA sequencing of tumors identified tenascin C (TNC) as a candidate obesity-related serum tissue environment marker with elevated expression in tumors of HFD-fed mice. Serum TNC levels were greater in HFD-fed mice than in ND-fed mice. In pancreatic cancer patients, serum TNC levels were greater than those in controls. The TNC-high group had more metabolic disorders and greater CA19-9 levels than did the TNC-low group. There was no relationship between serum TNC levels and disease stage. Among 77 metastatic patients treated with chemotherapy, a high serum TNC concentration was an independent poor prognostic factor. Pancreatic cancer patients with high serum TNC levels experienced progression more rapidly.

Association of Tenascin-C Gene Polymorphisms with Risk of Acute Coronary Syndrome in South Indian Population: A Case-Control Genetic Association Study.

Background: The extracellular matrix (ECM) glycoprotein changes are associated with the pathogenesis and complications of atherosclerosis, leading to acute coronary syndrome (ACS). Tenascin-C (TNC), an ECM protein, has been implemented in the pathogenesis, diagnosis, and prognosis of patients with cardiovascular disease. Aim: The study aimed to compare the genetic variants of the TNC gene (rs13321, rs2104772, and rs12347433) between South Indians with ACS and healthy participants. Materials and Methods: This case-control study recruited 150 ACS patients as cases and 150 healthy participants as controls. TNC genotyping was performed using TaqMan 5'-exonuclease allele discrimination assay. Serum TNC levels were measured by enzyme-linked immunosorbent assay. Results: Serum TNC levels were significantly higher in cases compared with controls. No significant difference was observed in allele and genotype frequencies of rs13321, rs2104772, and rs12347433 between cases and controls, which was confirmed by dominant, recessive, codominant, and homozygotic genetic models. The patients with heterozygous genotypes of rs13321, rs2104772, and rs12347433 had significantly lower serum TNC levels than patients with respective homozygous genotypes. Haplotype analyses revealed that the C-T-A haplotype in the block of rs13321-rs12347433-rs2104772 was associated with lower ACS risk (OR = 0.33, 95% CI: 0.15 - 0.75; p = 0.005). Also, the C-T-T and G-T-A haplotypes of the TNC gene were associated with higher and lower serum TNC levels, respectively. Conclusion: Our study demonstrated no genetic association between single nucleotide polymorphisms of the TNC gene and ACS risk; however, the C-T-A haplotype of the TNC gene might be associated with reduced ACS risk in South Indians.

An investigation of the relationship between Behçet's disease and tenascin-C.

The study aimed to investigate serum tenascin-C levels and its relationship with pathogenesis of Behçet's disease (BD) with inflammatory processes. This prospective and analytical study included 34 BD patients (19 males, 15 females; mean age: 31.5±8.2 years; range, 18 to 48 years) who met the 2014 International Criteria for Behçet's Disease and had no comorbidities and 37 healthy volunteers (21 females, 16 males; mean age: 29.6±5.3 years; range, 21 to 45 years). Sex, age, age at diagnosis, clinical and laboratory data, medication use, and smoking history of the participants were recorded. Serum tenascin-C levels were measured using a commercially available tenascin-C enzyme-linked immunosorbent assay kit. There was no significant difference between the groups in terms of age (p=0.262) and sex (p=0.287). Serum tenascin-C levels were significantly lower in the BD group (10,824±7,612 pg/mL) compared to the control group (27,574±14,533 pg/mL, p<0.001). In the receiver operating characteristic analysis performed for the diagnostic value of tenascin-C level in BD, the sensitivity was determined as 79.4% and the specificity as 82.5% (p<0.001). No statistically significant difference was observed in tenascin-C levels in correlation with clinical characteristics, laboratory values, medication use, and smoking in the BD group. In contrast to other chronic inflammatory diseases, lower levels of tenascin-C were observed in patients with BD than in the healthy individuals, which can be attributed to the absence of prolonged chronic inflammatory course in BD. The fact that tenascin-C levels are high in other rheumatic inflammatory diseases but low in BD may be useful in the differential diagnosis of BD.

Assessment of Tenascin C levels in the serum of patients with bronchial asthma

Asthma is a heterogeneous disease that affects a large proportion of the global population and is distinguished by airway hyperresponsiveness to direct and indirect stimulations. It is a multifactorial disease that is triggered by heredity and environmental causes. Tenascin C (TNC) is an extracellular matrix glycoprotein that promotes inflammatory cell migration from the interstitium to the airways. Stimulation of TNC is through cytokines from T helper 2 (Th2) cells, in addition, it proliferates within basement membranes of the airways in asthmatic patients. This study aimed to determine whether serum TNC can be used as a novel biomarker for asthma diagnosis and to evaluate the association between serum TNC measurement and asthma severity. This case-control study included 64 patients with mild to severe bronchial asthma, diagnosed according to GINA 2022, referred to the Allergy and Clinical Immunology outpatient clinic at Ain Shams University Hospital, and 64 normal subjects as controls. Serum TNC levels were measured by ELISA. Serum TNC levels were significantly higher among bronchial asthma patients than controls (p ˂0.001). The sensitivity of serum TNC measurement in the diagnosis of bronchial asthma was 93.75%, the specificity 60.94%, and the negative predictive value 90.7%. Besides, a significant relation was found between serum TNC levels and the severity of bronchial asthma (p=0.004), as elevated serum TNC levels were the highest among severe asthmatic patients. In conclusion, the results gained in this study revealed that serum TNC level could be proposed as a potential biomarker for the diagnosis of bronchial asthma and a potential predictor of disease severity.

Increasing circulating levels of Tenascin C in response to the Wingate anaerobic test.

Tenascin C (TNC) is a large extracellular matrix glycoprotein. It is involved in development and upregulated both during tissue repair and in several pathological conditions, including cardiovascular disease. Extracellular matrix proteins play a role in promoting exercise responses, leading to adaptation, regeneration, and repair. The main goal of this study was to investigate whether a short anaerobic effort leads to increased levels of TNC in serum. Thirty-nine healthy men performed a Wingate test followed by a muscle biopsy. Myoblasts were isolated from the muscle biopsies and differentiated to myotubes ex vivo. TNC RNA was quantified in the biopsies, myotubes and myoblasts using RNA sequencing. Blood samples were drawn before and 5 min after the Wingate test. Serum TNC levels were measured using enzyme-linked immunosorbent assay. After the Wingate test, serum TNC increased on average by 23% [15-33], median [interquartile range]; PWilcoxon < 0.0001. This increase is correlated with peak power output and power drop, but not with VO2max . TNC RNA expression is higher in myoblasts and myotubes compared to skeletal muscle tissue. TNC is secreted systemically as a response to the Wingate anaerobic test in healthy males. The response was positively correlated with peak power and power drop, but not with VO2max which implicates a relation to mechanical strain and/or blood flow. With higher expression in undifferentiated myoblast cells than muscle tissue, it is likely that TNC plays a role in muscle tissue remodelling in humans. Our findings open for research on how TNC contributes to exercise adaptation.

Tenascin-C and Interleukin-17 Up-regulation in Axial Spondyloarthritis Patients

Background: Axial spondyloarthritis (axSpA) is an inflammatory, systemic rheumatic condition that mostly affects the axial skeleton. Tenascin-C (TN-C) is a hexameric glycoprotein of considerable size, upregulated in many inflammatory conditions, while Interleukin-17 (IL-17) a cytokine that plays an important role in SpA symptoms. Objective: to investigate the upregulation between the serum levels of TN-C and IL-17 in Iraqi axSpA patients and the disease characteristics. Patients and Methods: Seventy-four axSpA patients and 28 matched controls were studied. Fifty-four patients received a tumor necrosis factor inhibitor (TNFi) and 20 did not. Serum TN-C and IL-17 concentrations were determined using the ELISA technique. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was assessed. For statistical tests, Chi Square, Mann Whitney, Independent Samples T, and Pearson's correlation tests are used. Results: Patients mean age was 35.6±0.9 years, 65 males and 9 females, and disease duration was 5.18±0.6 years. 47.4% were smokers, 47% had inflammatory low back pain, and HLA-B27 was present in 91%. BASDAI mean was 6.1±0.4 in non-TNFi and 2.6±0.3 in those on TNFi. The serum TN-C concentration was significantly increased in patients, especially those on non-TNFi (79±9.6 pg/mL) compared to those on TNFi (69.1±3.2 pg/mL) and control (53±3.9 pg/mL) (p=0.003). Serum IL-17 was significantly elevated in those receiving TNFi (877.9±257 pg/mL) compared to non-TNFi (487.2±234 pg/mL) and control (182.4±36.6 pg/mL) (p=0.033). The TN-C significantly correlated with erythrocyte sedimentation rate (r=0.27, p=0.02) and with hemoglobin (Hb) concentration (r=0.26, p=0.02). TN-C and IL-17 were non-significantly related (r=0.14, p=0.2). Conclusions: axSpA Patients demonstrated high levels of serum TN-C, particularly in those not receiving TNFi, and high IL-17 levels in those receiving TNFi, suggesting that there is an association with tissue injury from the disease and stimulation of immunological and resident tissue cells. Patients who had not received TNFi showed significantly higher disease activity than others.

Serum Tenascin-C and Alarin Levels Are Associated with Cardiovascular Diseases in Type 2 Diabetes Mellitus.

Background Tenascin-C (TNC), an extracellular matrix glycoprotein, is elevated in inflammatory and cardiovascular pathologies, whereas alarin, a novel orexigenic peptide, participates in insulin resistance and glycometabolism. The roles of these molecules in individuals with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), clinical conditions associating with metabolic disorders, and chronic inflammation, remain controversial. Our study aimed at determining the potential role of TNC and alarin in CVD adult patients with T2DM. Methods This was a cross-sectional study. Basic and clinical information for 250 patients with T2DM were analyzed. Based on their cardiovascular disease status, participants were assigned into the CVD and non-CVD groups. Serum TNC and alarin levels were assessed by enzyme-linked immunosorbent assay (ELISA). Results Serum TNC and alarin concentrations in the CVD group were significantly higher than those of the non-CVD group. Moreover, serum TNC levels were positively correlated with age, waist circumference, and waist-hip ratio; however, they were negatively correlated with TC, LDL-C, and eGFR levels. Alarin levels were positively correlated with BMI, waist circumference, and hip circumference. In logistic regression models, TNC and alarin were also established to be independent determinants for CVD in T2DM patients and their increases were associated with CVD severity. Receiver operating characteristic (ROC) curve analysis showed that the area under curve (AUC) values for TNC and alarin were 0.68 and 0.67, respectively. TNC and alarin were good predictors of CVD occurrence. When the cutoff value for TNC was 134.05 pg/mL, its sensitivity was 69.47% while its specificity was 61.29%. When the cutoff value for alarin was 142.69 pg/mL, sensitivity and specificity were 38.95% and 90.97%, respectively. Conclusion Elevated TNC and alarin levels are independently associated with the occurrence and severity of CVD in T2DM individuals. Therefore, these two biomarkers are potential diagnostic and prognostic indicators for CVD in diabetics.

Evaluation of periostin, fibronectin and tenascin-C in patients chronic otitis media with cholesteatoma

BackgroundAlthough many studies have investigated the mechanisms of cholesteatoma formation, its pathogenesis remains unclear. The aim of this study was to evaluate the levels of periostin, fibronectin and tenascin-C, which are involved in many mechanisms, such as cell adhesion, cell differentiation, inflammation, fibrosis, angiogenesis and cell proliferation, in patients with chronic otitis media (COM). A total of 80 participants, 65 COM patients undergoing surgery and 15 healthcare personnel volunteers serving as controls, were included in this study. The participants were divided into four groups: cholesteatoma, granulation, avivation and control group. The serum periostin, fibronectin and tenascin-C levels of all participants were determined biochemically. Histopathological evaluation of tissue samples and 20 skin samples used as controls was performed by immunohistochemistry.ResultsOf the 65 patients, 22 presented with cholesteatoma, 15 with granulation tissue and 28 with the edge of the tympanic membrane perforation freshening tissue. There were no significant differences in serum periostin, fibronectin and tenascin-C levels between the groups. In the immunohistochemical evaluation, fibronectin and periostin staining was significantly more intense in the cholesteatoma group than in the other groups (p = 0.001). Epithelial tenascin-C staining was significantly more intense in the avivation group than in the other groups (p = 0.041).ConclusionThe levels of periostin and fibronectin were higher in cholesteatoma tissue than in other forms of chronic otitis and skin tissue. This suggests that they may be involved in the mechanism of cholesteatoma formation. These proteins could be used as biomarkers in the diagnosis and treatment of cholesteatoma.

The expression and role of tenascin C in abdominal aortic aneurysm formation and progression.

OBJECTIVESUp-regulation of tenascin C (TNC), a matricellular protein, produced mainly by vascular smooth muscle cells (VSMC), is associated with the progression and dilation of abdominal aortic aneurysms (AAA). The aims of this study were (i) to evaluate whether serum levels of TNC in patients with AAA patients correlate with aortic diameter and (ii) to clarify the role of TNC in formation and progression of AAA in a murine model.METHODSIn 15 patients with AAA serum levels of TNC were measured and correlated with aortic diameters. Moreover, in a murine calcium chloride AAA model, the impact of TNC deficiency on AAA diameter was evaluated. Finally, human VSMC were incubated with TNC to clarify its regulating potential.RESULTSIn the clinical cohort, there was a trend of correlation between serum TNC levels and AAA diameter (P = 0.055). TNC knock out mice with AAA showed significantly lower diameter ratios compared to the wild-type group (WT) 3 weeks (P < 0.05) and 10 weeks (P < 0.05) after AAA induction. Immunohistochemistry revealed increased TNC expression in aortic tissue from WT with AAA as compared sham-operated mice. Furthermore, WT with AAA showed a more disrupted Elastin structure than TNC knock out mice 10 weeks after AAA induction. In human aortic VSMC, TNC incubation induced expression of remodelling associated proteins.CONCLUSIONSTNC might play a causative role in the formation, dilation and progression of AAA. Our results indicate that TNC might be a biomarker as well as a potential therapeutic target in the treatment of AAA.

Associations Between Tenascin-C and Testosterone Deficiency in Men with Major Depressive Disorder: A Cross-Sectional Retrospective Study.

BackgroundElevated levels of tenascin-C are linked to increased risk and severity of major depressive disorder (MDD), while testosterone shows a protective effect. The present study explored associations between serum levels of tenascin-C and testosterone in Chinese men with MDD.MethodsTestosterone and tenascin-C levels were measured in sera of 412 men with MDD and 237 age- and sex-matched controls. Serum levels of thyroid hormone, lipids, and high-sensitivity C-reactive protein (hs-CRP) were also quantified. Potential associations were examined using covariance, subgroup analysis, and multivariate linear regression analyses.ResultsSignificantly higher concentrations of tenascin-C were detected in sera of subjects with MDD than in controls. Among subjects with MDD, testosterone concentrations inversely correlated with tenascin-C levels. This relationship was observed when patients were stratified by age at onset; duration or severity of depression; or concentration of thyroid hormones, low- or high-density lipoprotein, or hs-CRP. The negative association remained even when the statistical model was adjusted for age, smoking status, alcohol use, and body mass index. Linear regression with bootstrap resampling confirmed that high tenascin-C levels inversely correlated with testosterone levels.ConclusionIn men with MDD, high tenascin-C concentrations correlate with testosterone deficiency. The combination of elevated tenascin-C and testosterone deficiency may be associated with MDD progression.

Serum tenascin-c in systemic lupus erythematosus and association with clinical expression of the disease

Background: Tenascin-C (TN-C) is a pro-inflammatory glycoprotein with various biological functions. TN-C plays a major role in cell adhesion, migration, proliferation, and cellular signaling through the induction of pro-inflammatory cytokines. Aim of the Work: This study was designed to investigate the relationship between serum TN-C levels and disease activity in patients with systemic lupus erthromatosus. Subjects and Methods: This is a case–control observational study that was carried out on 68 participants and divided into two groups. Group A included 34 systemic lupus erythematosus (SLE) patients and Group B included (34) apparently healthy volunteers. They were age and sex matched with the patients. Clinical examination as well as routine laboratory investigations confirmed their healthy status. All patients were subjected to full history taking, through clinical examination, laboratory investigations as C-reactive protein, erythrocyte sedimentation rate, C3, C4, ANA, and anti-dsDNA. Serum TN-C estimation of serum TN-C was done for SLE patients and the control group using double-antibody sandwich enzyme-linked immunosorbent assay. Disease activity of SLE patients was assessed according to SLE disease activity index 2000 score. Results: Serum level of TN-C was higher in SLE patients than healthy control but with no statistically significant difference (P > 0.05). There was highly statistically significant difference (P Conclusion: Serum TN-C level is elevated in SLE patients and correlates with disease activity which indicates its possible role in SLE pathogenesis. Thus, TN-C may provide a novel research target for the pathogenesis and therapy of SLE.

Elevated Tenascin-C Serum Levels in Patients With Axial Spondyloarthritis.

This study aimed to examine serum tenascin C (TNC) in different subsets of axial spondyloarthritis (axSpA) patients. Sixty-one patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria for axSpA and 20 healthy subjects (HS) were included in study. Based on imaging, patients were classified as non-radiographic (n=16) and radiographic (n=45) axSpA. TNC serum levels were determined by ELISA. Disease-related factors including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and C-reactive protein (CRP) levels, were determined. TNC levels were elevated in axSpA patients [535.3 (457.7-677.2) ng/ml] compared to HS [432.1 (329.1-565.9) ng/ml, p=0.007]. Dividing axSpA into radiographic and non-radiographic subsets, the difference in TNC was observed between the radiographic subset and HS [535.3 (434.5-677.2) vs. 432.1 (329.1-565.9) ng/ml, p=0.022]. TNC levels did not correlate with disease activity measures (serum CRP or BASDAI). Nevertheless, the weak correlation of TNC levels with different disease stages (r=0.25, p=0.025) was found, with the highest levels in patients with syndesmophytes. TNC levels are elevated across various subsets of axSpA, and although not related to systemic disease activity, TNC levels might reflect chronic structural spinal changes in axSpA patients. However, its specific role in bone metabolism should be elucidated in further studies.

Serum tenascin-C levels in atrium predict atrial structural remodeling processes in patients with atrial fibrillation.

Fibro-inflammatory processes in the extracellular matrix are closely associated with progressive structural remodeling in atrial fibrillation (AF). Serum concentrations of tenascin-C (TNC), an extracellular matrix glycoprotein, and of high-sensitivity C-reactive protein (CRP) might serve as a marker of remodeling and progressive inflammation of the aorta and in myocardial diseases. This study aimed to clarify relationships between TNC and CRP in patients with AF. This study included 38 patients with AF and five controls without left ventricular dysfunction who underwent catheter ablation. Blood was collected immediately before ablation from the left atrium (LA), right atrium (RA), and femoral artery (FA), and left and right atrial pressure was measured. Levels of TNC in the LA (TNC-LA), RA (TNC-RA), and FA (TNC-FA) and high-sensitivity C-reactive protein (CRP) were measured. Atrial size was also determined by echocardiography. Levels of TNC corrected by atrial size were maximal in the LA, followed by the RA (3.69 ± 0.32 and 2.87 ± 0.38ng/mL/cm, respectively). Mean transverse diameter corrected by body surface area was larger and mean atrial pressure was greater in the LA than the RA. A relationship was found between CRP from the femoral vein and TNC-LA and TNC-RA, but not TNC-FA. None of TNC-LA, TNC-RA, or TNC-FA correlated with ANP or BNP in the femoral vein. Intracardiac (atrial) TNC expression plays an important role in the development of remodeling processes in the atrium with AF. Tenascin-C from the LA and RA (but not TNC, ANP, and BNPfrom FA) might serve as novel markers of these processes.

Tenascin-C Is Increased in Inflammatory Bowel Disease and Is Associated with response to Infliximab Therapy.

Tenascin-C (TNC) is an extracellular matrix glycoprotein expressed in response to inflammation and tissue damage. The role of TNC in patients with inflammatory bowel disease (IBD) is not well understood. In this study, we analyzed the expression of TNC in the inflamed mucosa of patients with ulcerative colitis (UC) and Crohn's disease (CD). Serum TNC levels were determined by the enzyme-linked immunosorbent assay (ELISA), and the levels of TNC in patients with different disease activities were compared. The expression of TNC was derived from a GEO dataset. THP-1 cells were stimulated with TNC to evaluate the proinflammatory role of TNC. We found higher TNC expression in the inflamed mucosa of patients with UC and CD compared with normal controls (NCs). TNC was mainly expressed in the stromal area of the intestinal mucosa. The median serum levels of TNC were significantly higher in UC (median 74.1 ng/ml, range 42.6–102.1 ng/ml) and CD (median 59.2 ng/ml, range 44.0–80.9 ng/ml). We also found that serum TNC levels were correlated with Mayo scores in UC and Crohn's disease activity index (CDAI) in CD. Through GSE14580, we demonstrated that patients who were nonresponsive to infliximab treatment had higher mucosal TNC mRNA expression. High TNC mRNA expression in the inflamed intestinal mucosa was associated with poor response to infliximab therapy in patients with UC. Furthermore, THP-1 cells stimulated with TNC showed increased expression of IL-6, but not TNF-α, IL-8, MCP-1, or IL-1β. Thus, increased TNC levels may participate in the pathogenesis of IBD and may serve as a biomarker for disease activity and response to treatment with infliximab.

P5579Pre-existing depression significantly improves after transcatheter aortic valve implantation (TAVI): analysis of long-term effects and screening for novel biomarkers

Abstract Background and aims Depression negatively affects symptom tolerance as well as clinical endpoints in cardiovascular diseases. For aortic stenosis (AS) patients undergoing Transcatheter Aortic Valve Implantation (TAVI), a reduction of pre-existing depression and anxiety in short term follow-up could be recently shown by our group. The current study was aimed to evaluate these effects in long-term follow-up and to screen for promising biomarkers, e.g., 5-Hydroxytryptamin (5-HT), Endothelin-1 (ET-1), neutrophil gelatinase associated lipocalin (NGAL) and Tenascin-C (Tn-C) variants. These molecules might reflect a pathophysiological link between reverse cardiac remodelling and mental state. Methods The study included 182 out of 226 patients who underwent TAVI at the University Hospital Jena since August 2016. Besides clinical parameters, the EuroQol questionnaire (EQ-5D), the Visual Analog Scale (VAS), the Clinical Frailty Scale (CFS) and, to specifically detect depression and anxiety, the Hospital Anxiety and Depression Scale (HADS-D) were assessed directly before TAVI, at 6-weeks, 6-month as well as 12- months follow-up. Blood samples were withdrawn before TAVI and during 6-weeks and 6-month follow-up. Results Study patients represented a typical moderate- to high-risk TAVI collective (n=182, mean age 78,1±7.9 years, 46,9% male, mean STS-Score 4.6±2,8). Before TAVI, analysis of HADS revealed ≥8 points, defined as pathologic, for depression and/or anxiety in 71 patients (39%) and for depression only in 46 patients (25.3%). In the depressive subgroup, there was a significant improvement after 6 weeks for depression (p&lt;0.001) and anxiety (p=0.006). BNP serum levels were significantly reduced (p=0.007) and 6-minutes' walk distance was significantly increased from a low level (p=0.008), VAS, CFS and 2 out of 5 parameters of the EQ-5D were significantly improved (p&lt;0.05). All observed short-term effects continued at stable levels over time. A pre-existing depression state was not associated with an increased long-term mortality rate, which was 14.8%. Circulating biomarker levels in depressive patients before and 6 weeks after TAVI revealed no significant differences. At the 6 months follow-up, only for C+ Tn-C there was a significant increase compared to both, the timepoint before TAVI (p=0.046) and the 6 weeks follow-up (p=0.033). Conclusions Already in short-term follow-up after successful TAVI, a remarkable decrease in depression could be detected using HADS. Especially in the depressive subgroup, the patients showed benefit also with respect to other surrogate parameters of mental health and functional performance. Interestingly, these effects were completely maintained not only in mid-term but also in long-term follow-up. We could show that the improvement of depression after TAVI is reflected by a delayed decrease of C+ Tn-C serum levels. C+ Tn-C can be suggested as promising biomarker possibly linked to reactive depression in somatic diseases.

The Predictive Role of Tenascin-C and Cellular Communication Network Factor 3 (CCN3) in Post Hepatectomy Liver Failure in a Rat Model and 50 Patients Following Partial Hepatectomy.

BackgroundMatricellular proteins of the extracellular matrix (ECM) include tenascin-C (TNC) and cellular communication network factor 3 (CCN3). This study aimed to investigate the role of TNC and CCN3 as prognostic factors for post hepatectomy liver failure (PHLF) in a rat model of partial hepatectomy and 50 patients following partial hepatectomy.Material/MethodsSprague-Dawley rats underwent 85% (n=53) or 90% hepatectomy (n=53) in the partial hepatectomy (PHx) model. TNC and CCN3 mRNA expression in residual liver tissue was evaluated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and enzyme-linked immunoassay (ELISA) determined the serum levels of TNC and CCN3. In 50 patients who underwent partial hepatectomy, TNC and CCN3 serum levels were measured on postoperative day 1 and day 3.ResultsIn the rat partial hepatectomy model, mRNA and serum levels of TNC and CCN3 were significantly increased within the first 24 h, and were higher in the 90% PHx group compared with the 85% PHx group. Fifty patients who underwent partial hepatectomy, included patients with PHLF (n=12) and patients without PHLF (n=38). Multivariate analysis confirmed that serum levels on postoperative day 3 TNChigh+CCN3high was a significant predictor of PHLF, which was associated with more than twice the risk of severe morbidity when compared with the low-risk patients (80% vs. 30%) and a significantly longer hospital stay (17 days vs. 8 days).ConclusionsFurther studies are needed to evaluate the potential role of the matricellular proteins, TNC and CCN3 as early clinical predictors for PHLF.

The Role of Serum Tenascin-C in Predicting In-Hospital Death in Acute Aortic Dissection

Tenascin-C (TNC) is involved in aortic disease pathophysiology. This study aims to evaluate TNC's value for predicting in-hospital death in acute aortic dissection (AD).We prospectively enrolled consecutive patients with suspected acute AD within 48 hours from symptom onset. Serum TNC and C-reactive protein (CRP) levels were examined on admission. Their baseline clinical characteristics and serum D-Dimer (DD) were collected. The endpoint was in-hospital death from AD.In the study cohort,78 survivors and 31 non-survivors with acute AD were enrolled. Compared to survivors, elevated median levels of serum TNC (141.10 pg/mL versus 75.30 pg/mL, P < 0.001), DD (8.74 μg/mL versus 4.58 μg/mL, P < 0.001), and CRP (19.20 mg/L versus 13.40 mg/L, P < 0.001) were found in non-survivors. Multiple logistic regressions revealed TNC, DD, and CRP were independent predictors of in-hospital death from acute AD. The OR and 95% CI were 1.038, 1.017-1.055; 1.084, 1.009-1.165 and 1.386, 1.107-1.643, respectively. Furthermore, TNC's sensitivity and specificity in predicting in-hospital death in acute AD were 83.87% and 83.33%. The combination of TNC and DD can improve the sensitivity and specificity to 90.30% and 88.46%.TNC is a valuable biomarker for predicting in-hospital death from acute AD. The combination of TNC and DD can improve predictions of in-hospital death from acute AD.

The Significance of Serum S100A9 and TNC Levels as Biomarkers in Colorectal Cancer.

Purpose: The aim of this study was to evaluate the diagnostic value of S100A9 and tenascin-c (TNC) levels as colorectal cancer (CRC) biomarkers in several ways, including through screening tests, differentiation tests, combination with existing biomarkers (CEA and CA19-9), and serum level measurements before and after surgery.Materials and Methods: In this case-control study, S100A9 and TNC serum levels were measured in 460 participants: 258 CRC patients, 99 patients with benign colonic disease (BCD) and 103 healthy donors (HD).Results: The serum levels of S100A9 were 22.32 (14.88-29.55) ng/ml, 10.02 (5.83-14.15) ng/ml and 10.05 (7.68-15.34) ng/ml in the CRC, BCD and HD groups, respectively. The serum levels of TNC were 4.30 (2.12-6.04) ng/ml, 1.60 (1.06-2.30) ng/ml and 2.00 (1.37-3.00) ng/ml in the CRC, BCD and HD groups, respectively. Significantly higher levels of both biomarkers (S100A9 and TNC) were found in CRC patients (both p<0.001).Both S100A9 and TNC levels were superior to CEA and CA19-9 levels as CRC diagnostic biomarkers; the combination of S100A9, TNC and CEA levels was an excellent biomarker with 79.8% sensitivity and 89.6% specificity. The serum levels of S100A9 and TNC in CRC patients were significantly lower after surgery than before surgery (p<0.01).Conclusion: S100A9 and TNC levels could serve as diagnostic biomarkers of colorectal cancer.