Serum tenascin-C Research Articles

Serum tenascin-C predicts severity and outcome of acute intracerebral hemorrhage

BackgroundTenascin-C is a matricellular protein related to brain injury. We studied serum tenascin-C in acute intracerebral hemorrhage (ICH) and examined the associations with severity and outcome following the acute event. MethodsTenascin-C samples were obtained from 162 patients with acute hemorrhagic stroke and 162 healthy controls. Poor 90-day functional outcome was defined as modified Rankin Scale score > 2. Early neurological deterioration (END) and hematoma growth (HG) were recorded at 24 h. ResultsPatients had higher tenascin-C levels than controls. Tenascin-C levels were positively correlated with hematoma volume or National Institutes of Health Stroke Scale score at baseline. Elevated tenascin-C levels were independently associated with END, HG, 90-day mortality and poor functional outcome. Moreover, tenascin-C levels significantly predicted END, HG and 90-day outcomes under receiver operating characteristic curves. ConclusionsAn increase in serum tenascin-C level is associated with an adverse outcome in ICH patients, supporting the potential role of serum tenascin-C as a prognostic biomarker for hemorrhagic stroke.

Tenascin-C, a biomarker of disease activity in early ankylosing spondylitis.

Monocytes of patients with ankylosing spondylitis (AS) over-express toll-like receptor (TLR) 4. Tenascin-C (TNC) is an endogenous TLR4 ligand. Thus, we studied the serum and synovial fluid levels of TNC in AS. TNC was measured in serum of 36 AS patients (ASAS 2010 criteria) and 39 healthy controls by ELISA. Twenty-two patients were followed up after 3 months of standard treatment. Five paired serum-synovial fluid samples were also analyzed. Disease activity was assessed by BASDAI, ASDAS, swollen joint count, ESR, and CRP. All values are in median (IQR). Median age was 30 (20-35) years, and disease duration was 5.5 (1.3-10) years. Thirty-one were male. Twenty-five (69.5%) had peripheral arthritis. Median BASDAI was 5.3 (3.3-6.7). HLA B27 was positive in 34 (94.5%) cases. Median serum tenascin C levels were higher in AS [578.5 ng/ml] as compared to healthy controls [32.88 ng/ml, p < 0.0001]. Serum tenascin C levels correlated with ASDAS ESR [r = 0.367, p = 0.028] and ESR [r = 0.39, p = 0.035]. In patients with early disease (duration ≤ 5 years), serum levels had better correlation with ESR [r = 0.59, p = 0.009] and CRP [r = 0.479, p = 0.044]. On ROC analysis for active (PhGA ≥ 6) vs. inactive (PhGA ≤ 4) disease, tenascin-C (AUC = 0.60) performed as well as CRP (AUC = 0.65) and ESR (AUC = 0.73). Synovial fluid levels [11.61 (5.99-176.9) ng/ml] were lower than in serum [627.4 (488.5-779.1) ng/ml, p = 0.008]. Tenascin C fell levels with treatment [n = 11, 630.8 ng/ml to 376.4 ng/ml p = 0.0006] in treatment responders but not in non-responders [n = 11, 562.3 to 445.6, p = 0.33]. Serum TNC levels are raised in AS and may serve as marker of inflammation in early disease.

Studying Tenascin-C in systemic lupus erythematosus as a new biomarker for disease activity

Background The precise etiology and pathogenesis of systemic lupus erythematosus (SLE) remain unclear. Unpredictable flares and remissions and diverse serological and clinical manifestations are observed among patients with SLE and the challenge for the evaluation of disease activity and administration of appropriate treatment. Assessment of Tenascin-C (TNC) may reflect disease activity and/or early tissue damage in SLE. Aim The aim of this study was to examine whether TNC levels are useful as a predictive biomarker in SLE and to reflect their activity. Patients and methods In all, 50 patients with SLE (25 patients with active SLE, 25 patients with inactive SLE), and 25 age-matched and sex-matched healthy controls were enrolled in the study. Patients undergo clinical and laboratory assessment. Serum TNC was assessed by enzyme-linked immunosorbent assay. Our results The results have shown that patients with active SLE had a higher TNC level compared with inactive patients and healthy volunteers. Also the study showed a statistically significant positive correlation between TNC level and Systemic Lupus Erythematosus Disease Activity Index score. On the other hand, the TNC level correlated negatively with white blood cells, platelet counts, C3 and C4 levels, hemoglobin level, and disease status. Conclusion The increased serum tenascin level was found in patients with SLE and was correlated with certain clinical and laboratory immunoinflammatory parameters. So the estimation of serum Tenascin levels seems beneficial in the assessment of disease activity and progress in SLE patients as well as in the assessment of the efficacy of various treatment regimens used.

Correlation of tenascin-C concentrations in serum with outcome of traumatic brain injury in humans

BackgroundTenascin-C, a matricellular protein, is involved in brain injury. However, change of tenascin-C concentrations in peripheral blood remains unknown after traumatic brain injury (TBI). MethodsSerum tenascin-C concentrations were measured in 100 healthy controls, 108 severe TBI patients, 79 moderate TBI patients and 32 mild TBI patients. ResultsSerum tenascin-C concentrations of patients were significantly higher than those of controls. Tenascin-C concentrations negatively correlated with Glasgow Coma Scale (GCS) scores in all patients (r=−0.658, P<0.001). In severe TBI patients, tenascin-C in serum significantly discriminated patients at risk of 6-month mortality (area under curve, 0.821; 95% confidence interval, 0.735–0.888) and poor outcome (Glasgow Outcome Scale score of 1–3) (area under curve, 0.833; 95% confidence interval, 0.749–0.898) and emerged as an independent predictor for 6-month mortality (odds ratio, 1.114; 95% confidence interval, 1.008–1.233; P=0.005), overall survival (hazard ratio, 1.085; 95% confidence interval, 1.010–1.166; P=0.003) and unfavorable outcome (odds ratio, 1.049; 95% confidence interval, 1.014–1.076; P=0.001). By receiver-operating characteristic analysis, serum tenascin-C concentrations had similar prognostic value compared with GCS scores. ConclusionsEnhanced serum tenascin-C concentrations are closely related to trauma severity and clinical outcomes, substantializing tenascin-C as a potential prognostic biomarker after TBI.

Relation between coronary artery calcium score and serum tenascin-C level in patients without known coronary artery disease.

Presence of coronary artery disease (CAD) also in subjects without traditional risk factors leads to a search for new risk factors. Tenascin-C (TNC), an extracellular matrix glycoprotein is normally found in very low concentrations in tissues and serum of adults, whereas its expression is enhanced in case of pathological conditions accompanied by inflammation. This study aimed to investigate the relation between coronary artery calcium score (CACS)and serum TNC level. Ninety patients (age range, 18-75 years) presenting with chest pain but without known CAD were divided according to their CACSs as control (CACS = 0, n = 30), low CACS (CACS between 0 and 400, n = 30), and high CACS (CACS ≥ 400, n = 30) groups. The patients were questioned about risk factors and underwent laboratory analyses for biochemical parameters including TNC. The mean TNC level was significantly higher in the high CACS group as compared to both the low CACS group and the control group [4.7 (0.03-30.7), 28 (0.7-212) and 84 (2-456) ng/mL, respectively; P < 0.01]. A positive correlation was determined between serum TNC level and CACS (r = 0.641, P < 0.001). In the ROC curve analysis, when the cut-off value for TNC was accepted as 8.09 ng/mL, the sensitivity and specificity in detecting patients with CACS > 100 (moderate or significant calcification) were 72% and 82%, respectively. A significant relationship was found between CACS and serum TNC level. Thus, measurement of TNC level can be used in determining elevated CACS and thereby the risk for CAD.

Preventive effects of cilostazol against the development of shunt-dependent hydrocephalus after subarachnoid hemorrhage.

OBJECTIVE Chronic hydrocephalus develops in association with the induction of tenascin-C (TNC), a matricellular protein, after aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to examine if cilostazol, a selective inhibitor of phosphodiesterase Type III, suppresses the development of chronic hydrocephalus by inhibiting TNC induction in aneurysmal SAH patients. METHODS The authors retrospectively reviewed the factors influencing the development of chronic shunt-dependent hydrocephalus in 87 patients with Fisher Grade 3 SAH using multivariate logistic regression analyses. Cilostazol (50 or 100 mg administered 2 or 3 times per day) was administered from the day following aneurysmal obliteration according to the preference of the attending neurosurgeon. As a separate study, the effects of different dosages of cilostazol on the serum TNC levels were chronologically examined from Days 1 to 12 in 38 SAH patients with Fisher Grade 3 SAH. RESULTS Chronic hydrocephalus occurred in 12 of 36 (33.3%), 5 of 39 (12.8%), and 1 of 12 (8.3%) patients in the 0 mg/day, 100 to 200 mg/day, and 300 mg/day cilostazol groups, respectively. The multivariate analyses showed that older age (OR 1.10, 95% CI 1.13-1.24; p = 0.012), acute hydrocephalus (OR 23.28, 95% CI 1.75-729.83; p = 0.016), and cilostazol (OR 0.23, 95% CI 0.05-0.93; p = 0.038) independently affected the development of chronic hydrocephalus. Higher dosages of cilostazol more effectively suppressed the serum TNC levels through Days 1 to 12 post-SAH. CONCLUSIONS Cilostazol may prevent the development of chronic hydrocephalus and reduce shunt surgery, possibly by the inhibition of TNC induction after SAH.

Pankreas adenokarsinomunda serum tenascin-C düzeyi potansiyel bir biyobelirteç midir?

Objective: Tenascin-C (TNC) is an extracellular matrix protein involved in the tissue construction. Its expression levels have been detected low levels in normal tissues, but high in many tumors. In this study, we aimed to determine the clinical significance of serum TNC levels in patients with pancreatic adenocarcinoma (PA). Materials and Methods: Thirty-three patients with histopathologically confirmed PA diagnosis and sex- and age-matched 30 healthy controls were included into the current study. Serum TNC levels were measured using Enzyme-Linked Immuno Sorbent Assay (ELISA) method. Results: Median age was 59 (range, 32-84). Of the patients, 61% were male, 70% had good performance status, and 68% had tumors localized at pancreas head. Pancreaticoduodenectomy and palliative surgery were performed in 5 (15%) and 4 (12%) of the 9 (27%) patients who underwent surgical procedure. Serum TNC levels were found to be significantly higher in patients compared with control group (p0.05). Similarly, it was shown that serum TNC levels had no effect on overall survival (p=0.31). Conclusions: Serum TNC level is a diagnostic biomarker for patients with PA. However, it has neither predictive nor prognostic value in this group of patients.

Tenascin- C: A Promising Marker in Identifying Patients with Cardiovascular and Pulmonary Remodeling

Objectives: Our aim was to study serum levels of tenascin-C (TnC ) in patients with pulmonary hypertension and left ventricular hypertrophy in order to explore its diagnostic utility for cardiac remodeling among elderly patients admitted at Ain Shams University hospitals, Egypt. Methods: A case control study was conducted on 279 elderly selected from Ain Shams University Hospital. They were classified into 3groups; (Group I): 105 cases suffering from pulmonary hypertension (PH), (Group II):114 cases suffering from systemic hypertension and (Group III): 60 apparently healthy subjects serving as control group. Group I was classified according to WHO classification into 4 classes. Group I was reclassified according to the disease severity into 2 subgroups. Group II was reclassified into 2 subgroups according to presence or absence of concomitant left ventricular hypertrophy (LVH). All subjects were subjected to history taking, clinical examination, echocardiograhic measurements (for cases only), TnC assay by enzyme linked immunosorbent assay (ELISA) and lipid profile. Results: Serum tenascin-C showed a highly significant elevation in PH and LVH cases than controls (p<0.001). In addition, (ROC) curve analysis revealed a superior performance of TnC in discrimination of PH cases from healthy controls at cut-off value of 0.3ng/mL with sensitivity (91.4%), specificity (100%). Moreover, the diagnostic performance of TnC in discriminating PH patient’s subgroups was best at cut-off value of 4.3ng/mL with sensitivity (89.3%), specificity (85.7%).Conclusion: Serum TnC is a promising diagnostic marker for identifying patients with tissue remodeling in PH and LVH.

Role of Tenascin-C as a Predictor of Left Ventricular Remodeling after Streptokinase in Patients with Acute Myocardial Infarction

We investigated clinical implications of serum tenascin-C (TN-C) levels in patients with acute myocardial infarction (AMI) treated with thrombolytic therapy Serum TN-C levels were measured by ELISA in 60 cases presented with acute STEMI and 20 normal controls. The mean serum TN-C level of AMI patients on admission (57.5 ng/ml) was significantly higher than that of controls (57.49 ± 19.89 ng/ml vs. 34 ± 3.02 ng/ml; p=0.0001), follow-up examination (mean: 6 months) revealed that 17 of 60 AMI (28%) patients showed left ventricular (LV) remodeling (20% end-diastolic volume increase), and in 6 (10%), major adverse cardiac events (MACE) were detected. By receiver-operating characteristic (ROC) analysis, TN-C levels clearly discriminated prediction of LV remodeling and MACE compared with other variables including creatine kinase-MB, and LV function. Diabetes and TN-C were correlated with MACE in our study. The findings suggest that serum TN-C levels might be useful in predicting LV remodeling and prognosis after AMI.

Relation between coronary artery calcium score and serum tenascin-C level in patients without known coronary artery disease

Objective Presence of coronary artery disease (CAD) also in subjects without traditional risk factors leads to a search for new risk factors. Tenascin-C (TNC), an extracellular matrix glycoprotein is normally found in very low concentrations in tissues and serum of adults, whereas its expression is enhanced in case of pathological conditions accompanied by inflammation. This study aimed to investigate the relation between coronary artery calcium score (CACS) and serum TNC level.Methods Ninety patients (age range, 18-75 years) presenting with chest pain but without known CAD were divided according to their CACSs as control (CACS = O, n = 30), low CACS (CACS between 0 and 400, n = 30), and high CACS (CACS ≥ 400, n = 30) groups. The patients were questioned about risk factors and underwent laboratory analyses for biochemical parameters including TNC.Results The mean TNC level was significantly higher in the high CACS group as compared to both the low CACS group and the control group [4.7 (0.03-30.7), 28 (0.7-212) and 84 (2-456) ng/mL, respectively; P < 0.01]. A positive correlation was determined between serum TNC level and CACS (r = 0.641, P < 0.001). In the ROC curve analysis, when the cut-off value for TNC was accepted as 8.09 ng/mL, the sensitivity and specificity in detecting patients with CACS > 100 (moderate or significant calcification) were 72% and 82%, respectively.Conclusion A significant relationship was found between CACS and serum TNC level. Thus, measurement of TNC level can be used in determining elevated CACS and thereby the risk for CAD.

Serum tenascin-C discriminates patients with active SLE from inactive patients and healthy controls and predicts the need to escalate immunosuppressive therapy: a cohort study.

IntroductionThe aim of this study was to examine whether circulating levels of the proinflammatory glycoprotein tenascin-C (TNC) are useful as an activity-specific or predictive biomarker in systemic lupus erythematosus (SLE).MethodsSerum TNC levels were determined by enzyme-linked immunosorbent assay at inception visit in a prospective cohort of 59 SLE patients, and in 65 healthy controls (HC). SLE patients were followed for a mean of 11 months, disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) and British Isles Lupus Assessment Group disease activity index (BILAG-2004), clinical and laboratory data were recorded every 3–6 months, and changes in glucocorticoids (GC) and immunosuppressants (IS) were recorded serially. We examined cross-sectionally the relationships between serum concentrations of TNC and SLE status, SLEDAI-2 K scores, strata of disease activity, and levels of conventional biomarkers [anti–double-stranded DNA (dsDNA), anti-nucleosome antibodies, C3 and C4]. We also explored the utility of TNC levels for predicting disease flares, defined as (i) new/increased GC, (ii) new/increased GC or IS, and (iii) increase in SLEDAI by ≥3 or (iv) BILAG A or B flare.ResultsThere was no significant difference in the mean levels of TNC between the SLE patients and HC. However, in SLE patients with active disease (SLEDAI ≥6), the TNC levels were significantly higher than in the HC (p = 0.004) or in patients with no/low disease activity (p = 0.004). In SLE patients, TNC levels were significantly associated with positivity of anti-dsDNA (p = 0.03) and anti-nucleosome antibodies (p = 0.008). Flares defined by a need to escalate immunosuppressive therapy were captured more frequently and earlier than flares defined by standard activity indices. Higher baseline levels of serum TNC presented a significantly greater risk of flare (i) [hazard ratio (HR) 1.39, 95 % confidence interval (CI) 1.11–1.73] or (ii) (HR 1.25, 95 % CI 1.02–1.52) but not of flares (iii) or (iv). The baseline serum TNC level was the single most important independent predictor of flare (i) compared with conventional biomarkers.ConclusionsTNC is not disease-specific, but it seems to indicate the activity of SLE and may predict the need to escalate immunosuppressive therapy. TNC levels may thus serve as a useful activity-specific and predictive biomarker in SLE.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0862-4) contains supplementary material, which is available to authorized users.

Value of serum tenascin-C in patients with acute myocardial infarction

BackgroundMyocardial infarction (MI) is defined as myocardial cell necrosis due to significant and sustained ischemia. TN-C is an extracellular matrix glycoprotein that is expressed in several important steps during the very early stage of cardiogenesis. TN-C is not normally expressed in the adult heart, but transiently appears during pathological conditions and plays important roles in tissue remodeling. AimTo study the role of TN-C in myocardial infarction patients and to evaluate its role as a predictor of HF in these patients. MethodsThis study was conducted on 45 cases uniformly divided into 3 closely matched (in age and sex) groups as follows: Group (I) includes 15 patients who were suffering from AMI; Group (II) includes 15 patients who were suffering from HF on top of MI; and Group (III) includes 15 healthy volunteers coming for regular annual checkup. 3–6ml venous blood was collected on the day of admission under complete aseptic conditions and stored at −70°C until assayed by ELISA. ResultsTN-C levels in the sera of patients with AMI Group (I) were significantly higher than those of healthy volunteers. Moreover, in Group I of AMI, a positive correlation between TN-C level on one side and CK, CK-MB and troponin T level on the other side was found. TN-C levels in the sera of patients with congestive heart failure on top of acute MI Group (II) were significantly higher than those of healthy volunteers. Pro-BNP levels in patients with heart failure Group (II) were significantly higher than those with AMI not complicated with heart failure Group (I). Levels of pro-BNP were also positively correlated with those of TN-C in patients with heart failure on top of AMI Group (II). ConclusionsSerum TN-C might be a novel marker reflecting active structural remodeling in the myocardium following infarction, with high TN-C levels at acute stages possibly predicting progression of LV remodeling. Also, the incorporation of a combination of serum TN-C and plasma BNP levels may improve risk stratification for congestive heart failure after AMI. Further studies on large scale are needed for more evaluation of TN-C role in HF.

Impact of serum tenascin-C on the aortic healing process during the chronic stage of type B acute aortic dissection

Impact of serum tenascin-C on the aortic healing process during the chronic stage of type B acute aortic dissection

Abstract O.31: Tenascin-C can be a Novel Prognostic Biomarker For Kawasaki Disease

Tenascin-C (TNC) is an extracellular matrix glycoprotein sparsely detected in normal but highly expressed in pathological condition associated with inflammation in variety of tissues. By taking advantage of its specific expression, TNC is applicable as a biomarker and a molecular imaging target for diagnosis of disease activity for ventricular remodeling. In blood vessels, the expression of TNC in normal is generally low but strong expression is linked with several pathological conditions such as pulmonary artery hypertension, coronary atherosclerotic intima, and aortic aneurysm/ dissection. We hypothesized that TNC could be useful for evaluating disease activity of Kawasaki Disease(KD). We measured serum level of TNC of 174 patients with KD using ELSA and found that the TNC level was significantly higher than that of the controls, and the initial treatment with intravenous immunoglobulin decreased the level. Combination of serum TNC and Kobayashi score increased the accuracy to identify cases at a high risk of unresponsiveness to high-dose intravenous immunoglobulin. Immunohistochemical analysis of autopsied cases showed that TNC was strongly expressed in coronary vascular lesion at acute stage of KD patients as well as in the Candida albicans-induced murine model of vasculitis/aneurysm. Biomechanical analysis demonstrated that vascular flexibility was reduced in TNC knockout mice. A combination of inflammation and mechanical stress to aorta induced dissecting aneurysm in TNC knockout mice. In vitro, TNC enhanced macrophage migration and cytokine synthesis, meanwhile TNC synthesis was up-regulated by various pro-inflammatory cytokines. These results suggest that TNC is expressed in vascular lesion of KD reflecting active inflammation, which has diverse functions to modulate not only inflammatory response but also regulate vascular remodeling and aneurysm formation. TNC could be a key molecule in pathophysiology and a promising biomarker of KD.

Tenascin-C Levels, A Toll-like Receptor 4 Ligand, in Enthesitis-related Arthritis Category of Juvenile Idiopathic Arthritis: A Cross-sectional and Longitudinal Study.

Monocytes of children with enthesitis-related arthritis (ERA) show Toll-like receptor 4 (TLR4) overexpression. Tenascin-C (TNC) is an extracellular matrix glycoprotein and acts as an endogenous TLR4 ligand. Thus, we studied the serum and synovial fluid (SF) levels of TNC in children with ERA. TNC was measured in the serum of 80 children with ERA satisfying the International League of Associations for Rheumatology criteria. Fifteen children were followed up while being treated with regular nonsteroidal antiinflammatory drug (NSAID) therapy and levels were reassessed at 3 months. Seventeen paired serum-SF samples and 25 healthy control serum samples were also analyzed. Disease activity was assessed by physician's global assessment (PGA), early morning stiffness (EMS), tender (TJC) and swollen joint counts (SJC), enthesitis score, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). The mean serum TNC level in patients with active disease (67.1 ± 44.9 ng/ml) was significantly higher than in those with inactive disease (40.6 ± 36.7 ng/ml, p = 0.01) and healthy controls (21 ± 15.2 ng/ml, p < 0.001). Levels of TNC were higher in HLA-B27-positive (58.4 ng/ml) versus -negative disease (20.4 ng/ml, p = 0.01). TNC levels correlated moderately with disease activity: PGA r = 0.4, EMS r = 0.34, TJC r = 0.4, SJC r = 0.46, ESR r = 0.42, and CRP r = 0.32. In receiver-operation characteristic analysis for active versus inactive diseases, TNC [area under the curve (AUC) = 0.754] was equivalent to ESR (AUC = 0.787) and CRP (AUC = 0.789). Regular NSAID therapy led to a significant fall in serum TNC levels at 3 months (p = 0.0003). The SF TNC level was 17.39 ng/ml, significantly lower than the paired serum values (p = 0.01). Serum TNC levels are significantly raised and correlate with various clinical and laboratory variables of disease activity in children with ERA. Regular NSAID therapy reduces the TNC levels, probably related to controlling disease activity.

Tenascin C levels in patients with mild and severe preeclampsia

Objective: To determine the serum tenascin-C (TN-C) levels in cases with mild and severe preeclampsia.Methods: Pregnant women were divided into three groups, namely healthy pregnants (Group 1, n = 20), pregnants with mild preeclampsia (Group 2, n = 20) and pregnants with severe preeclampsia (Group 3, n = 20). The groups were formed so as to match each other in terms of gestational week. From each pregnant woman, pre- and post-delivery blood samples were obtained to measure serum TN-C levels. The data were evaluated using the Kruskall–Wallis variance analysis. For the obtained values of p < 0.05, the groups were compared in pairs. A p value of < 0.017 was accepted as significant.Results: In Groups 1, 2 and 3, the prepartum TN-C levels were 5.02 ± 0.4 µg/ml, 12.8 ± 2.9 µg/ml and 33.8 ± 11.7 µg/ml, and in the postpartum TN-C levels were 4.7 ± 0.1 µg/ml, 11.7 ± 1.8 µg/ml and 50.6 ± 33.8 µg/ml, respectively. There was a significant difference between the groups in terms of the prepartum and postpartum TN-C levels (p < 0.017, Mann–Whitney U [MWU] test). There was also a significant difference in the prepartum TN-C levels between Groups 2 and 3 (p < 0.017, MWU test).Conclusions: The prepartum and postpartum TN-C levels were significantly higher in mild and severe preeclampsia than those in healthy pregnants.

The correlation between tenascin-C expression, and formation of intestinal stricture.

OBJECTIVE:A strong correlation exists between tenascin-C induction, and acute inflammation. Generally increased tenascin-C concentrations are correlated with various inflammatory, and infectious diseases. In patients with diagnosis of Inflammatory Bowel Disease (IBD) presence of tenascin-C in colonic mucosa demonstrates tissue repair, and its mucosal concentrations are correlated with local disease activity Therefore plasma levels of tenascin-C have been demonstrated to be a helpful indicator of the activity of inflammatory bowel diseases. In this study, firstly in the literature, we aimed to display the correlation between tenascin-C expression, and formation of intestinal stricture.METHODS:A total of 43 patients (male, n=19; 44.2%; and female, n=24, 55.8%) aged between 19, and 63 years, with clinically, endoscopically, radiologically, and histopathologically confirmed definitive diagnosis of Crohn’s disease who were examined, diagnosed, and treated in the Gastroenterology Clinic of Haydarpasa Numune Training and Research Hospital between January 2011, and April 2012 were investigated. Serum tenascin-C levels were measured using commercial sandwich enzyme-linked immunosorbent assay Human Tenascin-C Purified Protein kit (Chemicon, Millipore(R), USA). Study groups were categorized based on the type of the disease as inflammatory (n=17; 39.5%), obstructive (27.2%), and fistule formation (n=10; 23.3%) Crohn’s disease. For statistical analysis SPSS (Statistical Package for Social Sciences) Statistics 15 program was used.RESULTS:Median tenascin- C value in the obstructive group (6.57 ng/mL; range, 4.26-21.87 ng/mL) was statistically significantly higher than that detected in the inflammatory (1.74 ng/mL; range,1.29-3.16 ng/mL), and fistulizing (1.44 ng/mL; range, 0.74-2.47 ng/mL) groups (p=0.002).CONCLUSION:Intestinal fibroblasts have an important role in the stricture formation process in CD. Transforming growth factor (TGF)-b1 cytokine is in the center of this process. A strong correlation exists between tenascin-C induction, and acute inflammation. As a known fact, serum tenascin-C levels can be used in the determination of activity of IBD. Starting from this point, serum tenascin-C levels can be useful in the categorization of the Crohn’s disease without the need for invasive methods. In the future, studies with larger patient series investigating use of serum tenascin-C in the prediction of stricturing Crohn’s disease should be conducted.

Abstract 17315: Low Occurrence of Left Ventricular Reverse Remodeling and Poor Long-term Prognosis in Dilated Cardiomyopathy with Higher Immunohistological Expression of Myocardial Tenascin-C

Background: Tenascin-C (TN-C) is an extracellular matrix protein, and may regulate matrix organization during tissue remodeling. Although serum TN-C is reported as a prognostic biomarker in patients with dilated cardiomyopathy (DCM), the clinical significance of myocardial expression of TN-C remains undetermined. The objective of this study is to clarify the significance of myocardial TN-C expression on left ventricular (LV) remodeling and long-term prognosis in patients with DCM. Methods: Eighty consecutive patients in 2005 and 2006, who were diagnosed with DCM by excluding ischemic cardiomyopathy and secondary cardiomyopathy by coronary angiography and right ventricular endomyocardial biopsy, were analyzed. Those patients were followed up to 73±34 months, and their clinical data were obtained. Immunohistochemistry for TN-C was performed on stored biopsy specimens to examine the association of TN-C deposition with the occurrence of LV reverse remodeling as well as long-term mortality. Immunostained area of myocardial TN-C was measured densitometrically and calculated in percent by the fraction of TN-C stained area to the whole myocardium (TN-C area). LV reverse remodeling was defined as LV end-diastolic dimension ≤55 mm and fractional shortening ≥25% by 60 months after diagnosis. Results: TN-C area was 1.2±1.6% on average. Twenty-two patients (28%) underwent LV reverse remodeling. Patients with LV reverse remodeling showed less TN-C area at diagnosis than those without (TN-C area; 0.6±0.5 vs. 1.5±1.8%, p=0.021). Patients were divided into two groups according to the extent of TN-C area; high TN-C group (TN-C area≥1.5%, n=19) and low TN-C group (TN-C area&lt;1.5%, n=61). LV reverse remodeling occurred less frequently in high TN-C group compared with low TN-C group (5% vs 33%, p=0.01). Eleven patients (14%) died during the observation period. Kaplan-Meier analysis revealed high TN-C group had worse prognosis than low TN-C group (p=0.009). Conclusions: Patients with higher immunohistological expression of myocardial TN-C in DCM were characterized with lower occurrence of later LV reverse remodeling and poorer long-term prognosis. Myocardial TN-C may have some crucial role in LV remodeling process in patients with DCM.

Abstract 13037: Tenascin-c Modulates Inflammatory Response and Aggravate Ventricular Remodeling After Myocardial Infarction in Mice Model

Tenascin-C (TN-C), an extracellular matrix glycoprotein, transiently appeared in myocardial tissue after acute myocardial infarction (AMI). We have previously reported that AMI patients with higher serum TN-C levels had worse long-term prognosis, suggesting TN-C may play important roles during the development of ventricular remodeling. However, the biological function of TN-C in ventricular remodeling is not fully understood. In this study, using TN-C knock-out(KO) mice, we investigated the effects of TN-C on LV remodeling and the biological function of TN-C during the acute phase of inflammatory responses after myocardial infarction. The 8 to 10 weeks old male wild type (WT) and TN-C knock-out (KO) mice were divided into 4 groups of WT+Sham, KO+Sham, WT+MI and KO+MI. Mice 12 weeks post-MI, the survival rate of both WT+MI (48.3%,14 of 29 mice) and KO+MI (55.6%,15 of 27 mice) groups had no significant difference. However, TN-C KO group had the better cardiac function than WT had (LVEF, 19.02±6.31% vs 10.63±4.43%; p&lt;0.001). Interstitial fibrosis at border area was significantly increased in the WT +MI group to compare with that of KO+MI, whereas the extent of fibrosis in the remote area revealed no significant difference between the two groups. By RT-PCR analysis, WT+MI group showed significantly higher expression of atrial natriuretic peptide at the border including infarcted areas than that of KO+MI at chronic MI phase. At acute phase, fluorescence activated cell sorting analysis showed that ratio of CD45+, CD11b+, Ly6c high pro-inflammatory monocyte were significantly decreased, whereas CD45+, F4/80+, CD206+, anti-inflammatory M2 macrophage were significantly increased in KO+MI compared with WT+MI group 7 days after MI. RT-PCR analysis showed that the expression of IL-10, an anti-inflammatory cytokine, was significantly higher in KO+MI than WT+MI. These findings suggest, TN-C aggravates the deterioration of LV function due to MI partly by modulating inflammation at acute phase.

Can Serum Tenascin-C Be Used as a Marker of Prognosis in Patients After Living Donor Liver Transplantation?

[Introduction] Tenascin-C (TN-C), an extracellular matrix glycoprotein, is not normally expressed in the liver but transiently reappears under various pathologic conditions to play important roles in tissue remodeling during inflammations such as chronic HCV hepatitis. Elevated serum TN-C levels in those patients were reported to reflect the tissue injury and remodeling. It is considered that serum TN-C could be effective as a marker of liver ischemia reperfusion injury and regeneration insufficiency in living donor liver transplantation (LDLT). In this study, TN-C was measured to clarify whether it could be used as a marker of liver regeneration insufficiency and prognosis in patients with LDLT. [Materials and Methods] The serum TN-C were analyzed in the 74 patients with LDLT between Jan. 2002 to Dec. 2005 at Mie University. TN-C on pre-op, post-op day 1, 7, 14 and 28 were measured. We analyzed various prognostic factors: age, sex, C-P, MELD, GRWR, warm ischemic time, cold ischemic time, blood loss, Plt, T-Bil and TN-C. ROC of TN-C was analyzed for 90- day death. Cox regression and Kaplan-Meier according to TN-C were analyzed for overall survival (OS). [Results] 9 patients died within post-op day 90. In the univariate analysis, C-P, MELD, Plt on day1, 14 and 28, T-Bil on day7, 14 and 28, TN-C on pre-, day7, 14 and 28 were prognostic factors. In the multivariate analyses used logistic regression, TN-C on day 14 (TNC14) was an only independent prognostic factor for 90- day death (p<0.05, odd’s ratio: 1.011). In analyzed ROC of TNC14, AUC was 0.814, sensitivity was 77.8% and specificity was 75.4%. With the optimum cutoff value of TNC14 was established at 190 ng/mL: 24 patients showed high TNC14 (≥190 ng/mL) and 50 patients showed low TNC14 (<190 ng/mL). GRWR was significantly lower in the high TNC14 group (median:0.973 vs 1.08, p<0.05).According to Cox regression for OS, TNC14 was a prognostic factor (median follow-up of month: 104, p<0.05,odd’s ratio: 1.004). Significant difference in OS between the low and high TNC14 groups (Log Rank: p<0.05) was noted. [Conclusions] Serum TNC14 can be used as the marker of prognosis in patients with LDLT. If graft size is smaller, serum TNC14 is potentially useful for early diagnosis of postoperative liver regeneration impairment.