Serum Levels Of Thrombospondin-1 Research Articles

Comparison of serum thrombospondin-1 and thrombospondin-2 levels among children with autism spectrum disorder and healthy controls

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, the etiology of which has not been clearly determined yet. There is increasing evidence that synaptic and dendritic changes are involved in the etiology of ASD. The aim of this study is to determine whether serum Thrombospondin-1 and Thrombospondin-2 differ between ASD patients and healthy controls. This study also investigates possible correlations between clinical symptomatology of ASD and serum Thrombospondin-1 and Thrombospondin-2 levels. Method: A total of 44 children with ASD and 21 healthy controls under 6 years of age were included in the study. Symptom severity and behavioral problems among children with ASD were evaluated by using Childhood Autism Rating Scale and Abnormal Behavior Checklist. Serum levels of Thrombospondin-1 and Thrombospondin-2 were measured by using commercial enzyme-linked immunosorbent assay kits. Result: No statistically significant differences were found between the two groups in terms of serum Thrombospondin-1 and Thrombospondin-2 levels. In addition, no correlation was determined between Thrombospondin-2 levels and clinical symptomatology and severity of ASD. However, the Thrombospondin-1 level was found to negatively correlated with the total score of Childhood Autism Rating Scale, inappropriate speech and stereotype subscale scores of Aberrant Behavior Checklist scale. Conclusion: Thrombospondin-1 might have a potential role in the etiopathogenesis of ASD. Further studies are required to clearly elucidate the association between Trombospondin-1 and ASD.

Decreased Thrombospondin-1 and Bone Morphogenetic Protein-4 Serum Levels as Potential Indices of Advanced Stage Lung Cancer.

Introduction: Lung cancer belongs to the most common carcinoma worldwide and is the leading cause of cancer-related death. Bone morphogenetic protein-4 (BMP-4) is extracellular signaling molecule involved in many important processes, including cell proliferation and mobility, apoptosis and angiogenesis. Thrombospondin-1 (TSP-1) belongs to the extracellular matrix proteins. It participates in the cell-to-cell and cell-to-matrix interactions and thus plays important role in tumor microenvironment for cancer development and metastasis formation. Aim: To investigate serum levels of TSP-1 and BMP-4 together with BMP-4 polymorphism in lung cancer patients. Material and Methods: A total of 111 patients (76 men) with newly diagnosed lung cancer, including 102 patients with non-small cell lung cancer and 9 patients with small-cell lung cancer. Advanced stage of lung cancer was diagnosed in 99 (89%) of patients: stage IV—in 48, stage IIIB—in 33, stage IIIA—in 18 patients; there were six patients with stage II and six patients with stage I. The control group consisted of 61 healthy persons. In all the subjects, serum levels of BMP-4 and TSP-1 were measured by ELISA. With a Real-Time PCR system genotyping of BMP-4 was performed. Results: BMP-4 and TSP-1 serum levels were significantly lower in the patients with lung cancer than in the controls (TSP-1:10,109.2 ± 9581 ng/mL vs. 11,415.09 ± 9781 ng/mL, p < 0.05; BMP-4: 138.35 ± 62.59 pg/mL vs. 226.68 ± 135.86 pg/mL p < 0.001). In lung cancer patients TSP-1 levels were lower in advanced stages (9282.07 ± 4900.78 ng/mL in the stages III-IV vs. 16,933.60 ± 6299.02 ng/mL in the stages I-II, p < 0.05) and in the patients with than without lymph nodes involvement (10,000.13 ± 9021.41 ng/mL vs. 18,497.75 ± 12,548.25 ng/mL, p = 0.01). There was no correlation between TSP-1 and BMP-4 serum levels. BMP-4 gene polymorphism did not influence the results of the study. Conclusion: Decreased levels of TSP-1 and BMP-4 may serve as potential indices of lung cancer, with additional importance of low TSP-1 level as a marker of advanced stage of the disease.

Variations in the Profiles of Vascular-Related Factors Among Different Sub-Types of Polycystic Ovarian Syndrome in Northern China.

Recently, a growing body of evidence has suggested that abnormal ovarian angiogenesis, secondary to the imbalance between various angiogenic markers, is involved in the pathogenesis of PCOS, and this has led to the use of various interventions (such as Diane-35) to restore the normal ovarian angiogenesis. Therefore, we conducted the current investigation to determine the role of such markers (endothelial growth factor (VEGF), endostatin (ES), and thrombospondin-1 (TSP-1)) in the pathogenesis of PCOS along with the associated changes in ovarian blood flow in patients with PCOS compared to healthy controls, both before and after a course of oral contraception. A total of 381 patients with PCOS and 98 healthy females of childbearing age were recruited from July 2014 to June 2017 at the Reproductive Center of the Second Affiliated Hospital of Harbin Medical University. The serum levels of VEGF, ES, and TSP-1 were determined by enzyme-linked immunosorbent assay, while ovarian perfusion was measured by the pulsatility index (PI) and resistance index (RI) by using transvaginal color Doppler ultrasound. Repeated analyses were carried out after 3 months of Diane-35 treatment. Post-treatment serum levels of luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio of patients with PCOS decreased significantly (P <0.05). The RI values of most PCOS patients increased after treatment (P<0.05), while PI was significantly increased in all patients (P<0.05). However, variable changes in the serum levels of TSP-1, VEGF, and ES after treatment were observed. Serum VEGF levels showed a negative correlation with serum LH/FSH ratio, T concentration, and ES (P <0.05), while ES levels were negatively correlated with serum T concentrations only (P<0.05). The markers of angiogenesis (VEGF, ES, and TSP-1) were expressed differently among PCOS patients, who also responded differently to the same course of Diane-35 treatment. This field still warrants further investigation to reach a more definitive conclusion.

Circulating Levels of Thrombospondin-1 and Thrombospondin-2 in Patients with Temporal Lobe Epilepsy Before and After Surgery.

To measure the serum levels of strong angiostatic and synaptogenetic molecules thrombospondin-1 (TSP-1) and thrombospondin-2 (TSP-2) in patients with temporal lobe epilepsy (TLE) before and after surgery. In this prospective study, 20 patients operated for TLE and 20 healthy subjects were included. Serum levels of TSP-1 and TSP-2 were measured using enzyme-linked immunosorbent assay (ELISA). Our findings showed that both groups had higher serum levels of both molecules "before" surgery than 10 days ?after? However, a significant difference was noted between ?before? and "after" surgery regarding TSP-1 (p=0.00001). Although a marked decrease was found "after" surgery with respect to TSP-2, the difference did not reach statistical significance (p=0.22). In patients with TLE, serum levels of both molecules ?before? surgery were found to be significantly higher than in healthy controls (TSP-1, p=0.00001; TSP-2, p=0.007). Serum levels of TSP-1 and TSP-2 are determined to be higher in patients with TLE than in healthy subjects, and the resection of epileptogenic tissues decreases the serum levels of these molecules. Future studies should involve a higher number of patients with serial serum levels of TSP-1 and TSP-2 at the long-term follow-up to correlate with seizure outcome.

Circulating levels of thrombospondin-1 and thrombospondin-2 in patients with common brain tumors

To measure serum levels of thrombospondin-1 (TSP-1) and thrombospondin-2 (TSP-2) in patients with common brain tumors, namely high-grade glioma (HGG), low-grade glioma (LGG), and meningioma. For this prospective study, a total of 56 patients were operated on for supratentorial gliomas and meningiomas, and 18 healthy subjects were evaluated. Serum levels of angiostatic molecules were measured with enzyme-linked immunosorbent assay. The results of patients were compared with those of healthy subjects. High serum levels of TSP-1 were seen in HGG, followed by LGG, meningioma groups, and controls. The only significant difference was found between HGGs and controls (p=0.004). There was a trend to decrease from HGG to controls. High serum levels of TSP-2 were seen in controls, followed by meningioma, LGG, and HGG. None of the patient groups showed significant differences compared with controls. Among the patient groups, TSP-2 was significantly higher in the meningioma group than the HGG group (p=0.01). No correlation was found with any of the molecules and the clinical parameters, including the presence of peritumoral edema or seizure, the anterior-posterior diameter of the tumor, and, more importantly, the grade of glioma. Our results indicate that TSP-2 might be more important than TSP-1 in preventing angiogenesis and a major angiostatic factor in glioma cells.

Decreased serum levels of thrombospondin-1 in female depressed patients.

AimThrombospondin‐1 (TSP‐1) is an astrocyte‐derived synaptogenesis‐related factor. It was previously reported to be increased by chronic treatment of electroconvulsive seizure, a model of electroconvulsive therapy (ECT), in rat hippocampus. The aim of this study was to examine whether serum levels of TSP‐1 are associated with depression and ECT.MethodsSerum TSP‐1 levels of major depressive disorder (MDD) patients (n = 36) and age‐ and gender‐matched healthy controls (n = 36) were measured by TSP‐1 ELISA. MDD patients were diagnosed according to the Diagnostics and Statistical Manual of Mental Disorders‐IV‐TR and underwent ECT. MDD patients were also analyzed for serum TSP‐1 levels pre‐ and post‐ECT. Evaluation of symptoms was obtained using the Hamilton Rating Scale for Depression.ResultsSerum TSP‐1 levels showed significant decreases specific to female MDD patients. However, TSP‐1 did not change pre‐ and post‐ECT, did not correlate with symptoms, nor was not affected by the dose of antidepressants.ConclusionSerum TSP‐1 is a possible female‐specific factor that reflects depressive trait, but not state.

Evaluation of Markers of Intravascular Hemolysis and Endothelial Dysfunction in Sickle Cell Anemia Patients with and without Hydroxyurea Therapy

Background: Sickle cell anemia (SCA) is characterized by chronic hemolysis and endothelial dysfunction (ED). Plasma hemoglobin (pHb) and its heme component released from intravascular hemolysis (IH) are among the most important factors contributing to ED. Unfortunately, the importance of IH to the development of an ED and the effects of hydroxyurea therapy on IH and ED in SCA remains unclear. Aims: We evaluated plasma levels of IH and ED markers among Brazilian SCA patients not receiving hydroxyurea therapy (HbSS), and compared with those of hydroxyurea-treated SCA patients (HbSS_HU) and healthy controls (HbAA). Methods: A cross-sectional study of 60 SCA consenting patients (32 HbSS and 28 HbSS_HU; 19-42 years) in steady state, who are being followed up at the Blood Center, Pernambuco (HEMOPE) and 32 HbAA controls. The IH markers were serum Lactate Dehydrogenase [LDH] and total heme measured by enzymatic colorimetric tests, and pHb measured by enzyme-linked immunosorbent assay (ELISA). The ED markers were plasma von Willebrand factor (vWF:Ag) and vWF ristocetin cofactor activity (vWF:Rco) levels measured by the latex enhanced immunoassay. The other ED markers were the antigen of vWF-cleaving protease (ADAMTS13:Ag), thrombospondin-1 and endothelin-1 levels measured by ELISA, and ADAMTS13 Activity (ADAMTS13:Act) measured by FRETS-VWF73 method. The study was approved by the Ethics Committee of the State University of Campinas and HEMOPE under protocol No: 1.863.428. Data were analyzed using GraphPad Prism 6. Results: The pHb and LDH were significantly increased in HbSS than HbSS_HU patients (Figures 1A and 1B). Plasma levels of vWF:Ag, vWF:Rco, serum levels of total heme, thrombospondin-1 and endothelin-1 were significantly increased in HbSS and HbSS_HU patients compared to HbAA controls (Figures 1C and 2A, 2B, 2E, 2F), while serum level of thrombospondin-1 level was elevated in HbSS than HbSS_HU patients (Figure 2E). Similarly, ADAMTS13:Ag levels and ADAMTS13 activity were significantly lower in HbSS and HbSS_HU patients than HbAA controls, while ADAMTS13 activity levels were significantly elevated in HbSS_HU patients compared to HbSS patients (Figure 2D). In HbSS_HU patients, the ADAMTS13:Act was negatively correlated with heme and LDH [r = -0.47, p = 0.013; and r = -0.44, p = 0.023 respectively]. In additional, heme was positively correlated with vWF:Ag and LDH [(r = 0.47, p = 0.017) and (r = 0.56, p = 0.003) respectively]. In HbSS patients, LDH and pHb were positively correlated (r = 0.44, p = 0.014). Conclusions: Hydroxyurea therapy was associated with a reduced levels of LDH, pHb and thrombospondin-1 levels, and increased levels of ADAMTS13 activity in SCA patients. Increased ADAMTS13 activity levels may be attributed to reduction of pHb and thrombospondin-1 levels because previous invitro studies have shown that thrombospondin-1 or pHb are bound to vWF. Thus, vWF is restrained from ADAMTS13 activity and cleavage, and hyperreactive vWF might accumulate as a consequence of inhibition of ADAMTS13 activity. Increased thrombospondin-1, pHb and hyperreactive vWF levels are proposed to participate in sickle cell adhesion and promote thrombotic complications. Therefore, our results demonstrate an additional clinical benefit for the use of hydroxyurea in these patients. Disclosures No relevant conflicts of interest to declare.

Decreased serum thrombospondin-1 and elevation of its autoantibody are associated with multiple exacerbated clinical manifestations in systemic lupus erythematosus.

The pathological effects of thrombospondin-1 (TSP-1) have been studied in many preclinical tumor models and rheumatoid arthritis. However, the role of TSP-1 and anti-thrombospondin-1 autoantibodies (ATSA) in systemic lupus erythematosus (SLE) has not been specifically defined. In this study, we investigated the clinical relevance and functional significance of TSP-1 and ATSA in SLE patients. Serum levels of TSP-1 and ATSA were measured by ELISA in 138 adult SLE patients and 60 healthy controls. Blood cell counts, rheumatoid factor (RF), immunoglobulins, erythrocyte sedimentation rate (ESR), complements, and SLE-related autoantibodies were measured by standard laboratory techniques. Disease activity was assessed by systemic lupus erythematosus disease activity index (SLEDAI). TSP-1 concentrations were significantly lower in SLE patients compared with those in healthy controls. A significant difference of TSP-1 was observed in the patients with serositis, C3 decrease, RF positive, leukocytopenia, and thrombocytopenia. The levels of TSP-1 showed a positive correlation with the number of leukocyte and thrombocyte, while a negative correlation with anti-dsDNA antibody, IgG, ESR, and SLEDAI. ATSA was observed in 58.7% (81/138) of SLE patients, which was significantly higher than that in healthy controls (7/60, p < 0.05). Patients with active SLE showed higher ATSA positivity (67.1%) than those with inactive disease (47.1%, p < 0.05). ATSA was positively correlated with anti-rRNP antibody, IgG, total protein, and C4. This study revealed the opposite clinical relevance of TSP-1 and its autoantibody in SLE for the first time. TSP-1 may play an anti-inflammatory and immunoregulatory role in SLE autoimmunity. ATSA increased more frequently in disease-active patients and was associated with more severe clinical manifestations, which implicated its antagonistic role on TSP-1 and its involvement in the pathogenesis of SLE.

Population Study Confirms Serum Proteins' Change and Reveals Diagnostic Values in Congenital Ventricular Septal Defect.

This study was designed to validate thrombospondin 1 (TSP-1), vascular endothelial-cadherin complex (VE-cad), insulin-like growth factor 2 (IGF-2), and amyloid precursor protein (APP) and assess their diagnostic value in ventricular septal defect (VSD). We investigated the serum levels of TSP-1, VE-cad, IGF-2, and APP by enzyme-linked immunosorbent assay in a hospital-based case-control study that included 40 VSD children and 40 healthy controls. Logistic regression analysis was applied to evaluate the relationship of the proteins and VSD, and receiver operating characteristic (ROC) curve was used to assess the diagnostic value of the significant proteins. The serum levels of TSP-1, VE-cad, and IGF-2 were significantly higher in VSD patients than those in healthy controls (p<0.05). Multivariate logistic regression analysis demonstrated that high levels of TSP-1, VE-cad, and IGF-2 were significantly associated with an increased risk of VSD [TSP-1 (OR 26.91, 95% CI 6.60-72.66, p<0.001), VE-cad (OR 11.91, 95% CI 3.90-36.36, p<0.001), IGF-2 (OR 3.25, 95% CI 1.25-8.43, p=0.015)]. Areas under the ROC curve for TSP-1, VE-cad, and IGF-2 were 0.985, 0.838, and 0.658, respectively. These data demonstrated that TSP-1, VE-cad, and IGF-2 were significantly associated with risk of VSD and manifested diagnostic values, which may provide new evidence for understanding the etiology and promote the early diagnosis and prevention of VSD.

High serum levels of thrombospondin-1 in patients with idiopathic interstitial pneumonia

Thrombospondin-1 (TSP-1), a multifunctional matricellular glycoprotein, can activate transforming growth factor-beta, an important profibrotic cytokine involved in various fibrotic diseases. TSP-1 is expressed in the lung tissue of animal models of bleomycin-induced pulmonary fibrosis and in patients with some interstitial lung diseases. The present study investigated the serum and bronchoalveolar lavage fluid (BALF) levels of TSP-1 in the idiopathic interstitial pneumonias (IIPs) and the relationship between these levels and other clinical factors. The TSP-1 in the serum and BALF were measured in 45 patients with pathologically diagnosed IIPs [22 with usual interstitial pneumonia (UIP), 23 patients with non-specific interstitial pneumonia (NSIP)], as well as in 28 patients with pulmonary sarcoidosis and 15 healthy volunteers using a competitive enzyme immunoassay. The expression and localization of TSP-1 in the lungs were analyzed by immunohistochemical staining. The serum TSP-1 levels were significantly higher in patients with IIPs than in either those with sarcoidosis or the controls. These levels correlated well with those of an angiogenic cytokine vascular endothelial growth factor while correlating inversely with the %VC. Positive immunostaining of TSP-1 was predominantly observed in the regenerated alveolar epithelium and alveolar macrophages in the lung. Our findings suggest that the circulating TSP-1 levels are associated with the presence of interstitial pneumonia, but further studies are required before we can definitively conclude that TSP-1 plays a role in the pathogenesis of these diseases.