Connective Tissue Growth Factor In Patients Research Articles

Connective Tissue Growth Factor in Patients with Coronary Heart Disease: a Pilot Study

AIM. To determine the concentration of connective tissue growth factor and assess the relationship of this index with a number of pathological conditions in elderly patients with CHD. MATERIAL AND METHODS. The study enrolled 50 patients older than 75 years with a diagnosis of coronary heart disease (CAD); most of them (71%) were women. The patients ranged in age from 75 to 96 years (mean age -87.8 years). The concentration of connective tissue growth factor (CTGF) in blood was determined by enzyme immunoassay. RESULTS AND DISCUSSION. In the group of CHD patients, the average CTGF concentration was 357.2 pg/ml, whereas in healthy young adults it was 1076.7 pg/ml (p=0.07). Only 7.9% of patients with CHD had CTGF level exceeding 1000 pg/ml, whereas in young subjects CTGF level exceeded 1000 pg/ml in 25% of cases. In patients with clinically significant CHD, CTGF concentration was significantly higher than in patients without CHD (p=0.001). A negative correlation was registered between the CTGF levels and the systolic (r = -0.25; p = 0.1) and diastolic (r = -0.36; p = 0.02) blood pressure. In the subgroup of patients with pneumosclerosis, the median CTGF concentration reached 190.7 pg/l, without it – 34.7 pg/ml (p = 0.03). A significant inverse correlation was found between the CTGF levels and glucose (r = -0.34; p = 0.03), total cholesterol (r = -0.49; p = 0.002) and LDL cholesterol (r = -0.40; p = 0.01) concentrations. This pilot study found a significant effect of CTGF on echocardiographic parameters and the course of CHD, and higher levels of CTGF in patients with pneumosclerosis. However, a small sample of patients and extremely variable CTGF values do not currently allow unequivocal conclusions to be drawn at this time about the role of this factor in various comorbid conditions. CONCLUSION. Further research is needed to establish the clinical significance of CTGF.

Correlation analysis between mechanical power, transforming growth factor-β1, and connective tissue growth factor levels in acute respiratory distress syndrome patients and their clinical significance in pulmonary structural remodeling.

Background:To identify the clinical correlations between mechanical power and transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in acute respiratory distress syndrome (ARDS) patients, their clinical significance in pulmonary structural remodeling in ARDS patients was investigated.Methods:Ninety-five patients with moderate or severe ARDS, who required mechanical ventilation therapy, were randomly selected among hospitalized patients from January 2017 to February 2019. Their mechanical power was monitored and recorded, the TGF-β1 and CTGF levels were detected by enzyme-linked immunosorbent assay (ELISA), their relevance was analyzed, and the relationship between mechanical power and 28-day survival rate was investigated. According to the high-resolution computed tomography (HRCT) examination, the patients were divided into an ARDS group and an ARDS pulmonary fibrosis (ARDS-PF) group. The differences in mechanical power, TGF-β1, and CTGF between the 2 groups were compared, and the significance of TGF-β1 and CTGF in the diagnosis of ARDS pulmonary interstitial fibrosis were evaluated.Results:A significant positive correlation between mechanical power and serum TGF-β1 and CTGF in patients with ARDS was found and the correlation coefficients were 0.424 and 0.581, respectively. The difference between mechanical power and 28-day survival rate was statistically significant (P < .05), while the area under the receiver operating characteristic curves of TGF-β1 and CTGF for the diagnosis of ARDS pulmonary fibrosis was 0.838 and 0.884, respectively (P < .05).Conclusion:A significant correlation between mechanical power and serum fibrosis biomarkers TGF-β1 and CTGF in ARDS patients was found, and its level was related to the survival prognosis of patients. Mechanical power, TGF-β1, and CTGF were clinically evaluated for the assessment of lung structural remodeling, such as ARDS pulmonary fibrosis. This study has particular significance to the early prevention of ventilator-induced lung injury and pulmonary fibrosis in patients with ARDS receiving mechanical ventilation.

Immunohistochemical Analysis of the Role Connective Tissue Growth Factor in Drug-induced Gingival Overgrowth in Response to Phenytoin, Cyclosporine, and Nifedipine.

Objective:To evaluate for the presence of connective tissue growth factor (CTGF) in drug (phenytoin, cyclosporine, and nifedipine)-induced gingival overgrowth (DIGO) and to compare it with healthy controls in the absence of overgrowth.Materials and Methods:Thirty-five patients were chosen for the study and segregated into study (25) and control groups (10). The study group consisted of phenytoin-induced (10), cyclosporine-induced (10), and nifedipine-induced (5) gingival overgrowth. After completing necessary medical evaluations, biopsy was done. The tissue samples were fixed in 10% formalin and then immunohistochemically evaluated for the presence of CTGF. The statistical analysis of the values was done using statistical package SPSS PC+ (Statistical Package for the Social Sciences, version 4.01).Results:The outcome of immunohistochemistry shows that DIGO samples express more CTGF than control group and phenytoin expresses more CTGF followed by nifedipine and cyclosporine.Conclusion:The study shows that there is an increase in the levels of CTGF in patients with DIGO in comparison to the control group without any gingival overgrowth. In the study, we compared the levels of CTGF in DIGO induced by three most commonly used drugs phenytoin, cyclosporine, and nifedipine. By comparing the levels of CTGF, we find that cyclosporine induces the production of least amount of CTGF. Therefore, it might be a more viable drug choice with reduced side effects.

The expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer

Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P=0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P=0.032) and DFS (P=0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy.

Connective Tissue Growth Factor: A Predictor of Recurrence after Catheter Ablation in Patients with Nonparoxysmal Atrial Fibrillation

Although catheter ablation can effectively eliminate atrial fibrillation (AF), the progression of atrial remodeling increases the risk of recurrence. We, therefore, examined the possibility of determining the postablation prognosis of patients with AF using biomarkers of atrial structural remodeling and serum connective tissue growth factor (CTGF) level, and measured its changes after catheter ablation. Subjects were 400 consecutive patients (308 with paroxysmal AF and 92 with nonparoxysmal AF [persistent and long-standing persistent AF]) who underwent catheter ablation for drug-resistant AF. Serum CTGF levels were measured before and 2 months after ablation. During the follow-up period of 20.5 ± 6.9 (8-30) months, 61 patients (66%) with nonparoxysmal AF and 95 patients (31%) with paroxysmal AF had recurrence after catheter ablation. Recurrence was associated with higher "baseline CTGF level" in patients with nonparoxysmal AF (936.5 ± 93.1 ng/mL vs 746.3 ± 56.9 ng/mL, P = 0.007) instead of patients with paroxysmal AF (851.6 ± 97.6 ng/mL vs 807.6 ± 99.1 ng/mL, P = 0.921). In nonparoxysmal AF, the recurrence subgroup also had larger left atrial diameter (LAD; 47.1 ± 5.2 mm vs 39.5 ± 4.3 mm, P = 0.035) compared with the nonrecurrence subgroup, and "baseline serum CTGF" and LAD were shown to be independent predictors for postablation recurrence by a Cox proportional hazards model. However, the 2-month postablation elevations of CTGF in patients with recurrence were not significantly different from that in patients without recurrence in nonparoxysmal AF. Our finding indicates that "baseline serum CTGF level" is an independent predictor for recurrence in patients with nonparoxysmal AF following catheter ablation. Two-month postablation elevation in CTGF has no association with recurrence.

Circulating Plasma Levels of Connective Tissue Growth Factor (CTGF) Are Elevated In Patients Afflicted with Rheumatoid Arthritis

AbstractAbstract 4320Biologic therapy for rheumatoid arthritis (RA) targets specific molecules that mediate and sustain the clinical manifestations of this complex illness. Compared with the general population, patients with RA are at an increased risk to develop cardiovascular diseases and the precise mechanism(s) of action remain obscure. This laboratory has proposed the existence of a pro-inflammatory axis in RA comprised by thrombospondin-1 (TSP1), transforming growth factor-beta (TGF-b) and CTGF. The present study evaluated plasma levels of TSP1, TGFb and CTGF in patients with RA by ELISA as well as specific cytokines and chemokines. CTGF plasma levels in RA patients (9.2 pg/ml mean, range 3.44–17.08) were found significantly increased (P<0.047) when compared to control subjects (mean 4.43 pg/ml, range 1.62–7.35). This is the first report in the medical literature documenting an augmented human plasma circulating levels of CTGF in RA. TSP1 circulating levels were found elevated in RA patients when compared to control subjects (mean 315 ng/ml vs. 25.4 ng/ml respectively, P<0.039). TGFb showed a trend for higher levels in patients with RA (10.1 ng/ml vs. 4.5 ng/m, P<0.095). The source CTGF in plasma could not be determined precisely but there is evidence of platelet activation in RA (Platelets 19:146, 2008), and TSP1 is the major content of the platelet a-granule (25%). CTGF can attract monocytes and both have been found co-localized in atherosclerotic plaques (Circulation 95, 831, 1997). IL-6 (P< 0.05), IL-12p70 (P<0.04), IP-10 (P<0.03) and MIP1b (P<0.016) were increased in the RA patients when compared to controls. Recent findings have placed platelet microparticles (Science 327; 580, 2010) as playing a major role (arsonists) in RA via monocytes and neutrophils. In summary, our results provide evidence that a pro-inflammatory axis is active in RA potentially contributing to cytokine changes as well as the cardiovascular disease associated with RA since TSP1 can induced IL-6 generation from monocytes and can activate inert TGFb on cell surfaces (fibroblasts and synoviocytes) with the subsequent up-regulation of CTGF. Disruption of the axis in experimental models of RA may prove to be an emerging therapeutic target in RA. Elucidation of the source of CTGF should provide as well key information for cell-targeting to prevent CTGF secretion into the blood milieu. Disclosures:No relevant conflicts of interest to declare.

Significance of Serum Connective Tissue Growth Factor in Patients with Hepatocellular Carcinoma and Relationship with Angiogenesis

Connective tissue growth factor (CTGF) expression changes variously in different human malignancies. The role of CTGF in hepatocellular carcinoma (HCC) is still not clear. The purpose of this study was to investigate the role of serum CTGF in patients with HCC and its correlation with HCC angiogenesis. CTGF, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) were measured by ELISA in preoperative sera of 88 patients with HCC with tumor resection and 39 healthy subjects. The relationship between CTGF and HCC clinicopathological parameters was observed. Prognostic significance of CTGF for survival of patients with HCC was assessed by Kaplan-Meier analysis. Preoperative serum CTGF level was significantly higher in patients with HCC than in healthy subjects (median, 63.5 vs. 11.4 ng/ml; P < 0.001). Serum CTGF correlated significantly with a series of clinicopathological parameters (big tumor size, advanced pathological tumor-node-metastasis stage, absence of tumor capsule, portal vein invasion). Serum CTGF showed a significant correlation with disease-free survival and overall survival of patients with HCC. Patients with high serum CTGF (>63.5 ng/ml) had a poorer disease-free survival time than the others (CTGF < or = 63.5 ng/ml; median disease-free survival time, 9.6 vs. 19.3 months). Patients with high serum CTGF had poorer overall survival time (median, 13.1 months) than the others (median, 21.7 months). In multivariate Cox analysis, CTGF was identified as an independent and significant prognostic factor of survival of HCC patients. Serum CTGF plays an important role in the progression of HCC. Serum CTGF may be a potential indicator of angiogenesis of HCC.

Expression of connective tissue growth factor in cardiomyocyte of young rats with heart failure and benazepril intervention

Ventricular remodeling is an important pathologic progress in almost all end stage heart failure (HF), and it is characterized by ventricular thickening and cardiac fibrosis with poor prognosis. The connective tissue growth factor (CTGF), a new growth factor with multi-function, has an important role in fibrosis of tissue and organs. It has been demonstrated that angiotensin-converting enzyme inhibitor (ACEI) can prevent the development of cardiomyocyte from remodeling and improve cardiac function. Researchers try to test the hypothesis that cardiac function improvement attributable to ACEI is associated with inhibiting expression of CTGF in patients with HF. The aim of this study was to observe changes in CTGF expression in cardiomyocyte of young rats with HF and effect of benazepril on CTGF. The animal model of HF was established by constriction of abdominal aorta. Five weeks old rats were randomly divided into 3 groups after 6 weeks of operation: (1) HF group without treatment (n = 15); (2) HF group where rats were treated with benazepril (n = 15); (3) sham-operated group (n = 15) where rats were administered benazepril through direct gastric gavage. After 4 weeks of treatment, the high frequency ultrasound was performed. The expression of CTGF was detected by immunohistochemistry and semi-quantative reverse transcription-polymerase chain reaction. Compared with the sham-operated group, left ventricular diastolic dimension (LVEDD), left ventricular systolic dimension (LVESD), interventricular septal thickness at end-diastole (IVSTd), interventricular septal thickness at end-systole (IVSTs), left ventricular posterior wall thickness at end-diastole (LVPWTd), left ventricular posterior wall thickness at end-systole (LVPWTs), left ventricular relative weight (LVRW), and right ventricular relative weight (RVRW) were all increased (P < 0.01), but ejection fraction (EF) and fractional shortening (FS) were decreased (P < 0.01). CTGF positive cells and expression of CTGF mRNA (0.609 +/- 0.065 vs 0.117 +/- 0.011, P < 0.01) were increased in HF group without treatment. LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW and RVRW were all decreased (P < 0.01), but FS and EF were increased (P < 0.01) in cases of HF treated with benazepril when compared with HF group without treatment. LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW and RVRW were higher (P < 0.01), EF and FS were lower (P < 0.01), CTGF positive cells and expression of CTGF mRNA were higher (P < 0.01) in HF group treated with benazepril than those of sham-operated group. The expression of CTGF was increased in the cardiomyocyte of young rats with HF and benazepril could prevent left ventricular from remodeling partly and improve cardiac function by inhibiting the expression of CTGF in cardiomyocyte in cases of HF.

Transforming growth factor-β pathway is activated in cholecystolithiasis

The etiopathogenesis of cholecystolithiasis is not well defined. Primary dysmotility of the organ, due to fibrosis of the gallbladder wall or muscular dysfunction, is suggested as a crucial factor. Transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) are involved in several fibrotic disorders and play a critical role in fibrogenesis, thereby changing the physiological function of the organs. In the present study we analyzed the role of TGF-beta and its downstream target CTGF in patients with cholecystolithiasis. Gallbladders were obtained from 16 individuals undergoing surgery for symptomatic cholecystolithiasis. Normal human gallbladder tissue samples from five individuals without any history of gallbladder disease were obtained through an organ donor transplantation program. Northern blot analysis, in situ hybridization, and immunohistochemistry were used to analyze the expression of TGF-beta1 and CTGF in the gallbladder tissue samples. By northern blot analysis there was an enhanced TGF-beta1 mRNA expression (eightfold increase; P < 0.04) in the cholecystolithiasis tissue samples in comparison with normal controls. There was also a concomitant increase in CTGF (41-fold increase; P < 0.01). By in situ hybridization and immunohistochemistry, CTGF mRNA was localized mainly in the mucosa layer, while intensive staining of the smooth muscle cells with TGF-beta1 and CTGF was observed. In addition, TGF-beta1 immunoreactivity was also localized in the fibroblasts and inflammatory cells. TGF-beta1 m-RNA levels showed a significant relationship with the degree of fibrosis in the tissue samples (P < 0.04, r = 0.5). Our data indicate that TGF-beta and CTGF are involved in ultrastructural tissue changes in patients with cholecystolithiasis. Activation of the "TGF-beta pathway," predominantly in the remaining mucosa and submucosal layer, indicates that extracellular matrix (ECM) synthesis with subsequent gallbladder wall fibrosis is an important step in gallbladder dysfunction in this disorder.

Serum levels of interleukin-6 and interleukin-10 correlate with total skin thickness score in patients with systemic sclerosis

Various growth factors and cytokines have been suggested to play a central role in initiating and developing fibrosis in systemic sclerosis (SSc). To determine which serum levels of soluble mediators are the most relevant to the degree of skin sclerosis in SSc, serum levels of various soluble mediators were examined by ELISA and correlated with skin thickening that was measured using modified Rodnan total skin thickness scoring (TSS) system. Serum levels of IL-4, IL-12, IL-13, tumor necrosis factor-α, connective tissue growth factor (CTGF), vascular endothelial growth factor, monocyte chemotactic protein-1, macrophage inflammatory protein-1β, soluble IL-6 receptor, and soluble L-selectin were higher in SSc patients than normal controls. Levels of IL-6, IL-10, and CTGF in patients with diffuse cutaneous SSc were higher than patients with limited cutaneous SSc and controls. Serum levels of IL-6 and IL-10 positively correlated with TSS in patients with SSc ( r=0.625, P<0.0001 and r=0.663, P<0.0001, respectively). In addition, IL-10 levels significantly correlated with pulmonary fibrosis. Thus, serum levels of IL-6 and IL-10 most strongly reflect the extent of skin thickening in SSc, suggesting that levels of IL-6 and IL-10 are useful serological indicators for skin fibrosis in SSc.