Serum Ang-2 Levels Research Articles

Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous.

Henoch-Schönlein purpura (HSP) and pediatric-onset systemic lupus erythematosus (pSLE) are closely associated with vasculitis and vascular diseases. This study aimed to investigate the clinical diagnostic values of Ang-1, Ang-2, and Tie2 for HSP and pSLE. We surveyed 82 HSP patients, 34 pSLE patients, and 10 healthy children. The expression levels of Ang-1, Ang-2, and Tie2 in the serum and urine were assessed using enzyme-linked immunosorbent assay. The diagnostic values of Ang-1, Ang-2, and Tie2 for HSP and pSLE were evaluated using receiver operating characteristic curve analysis. The results revealed that the serum and urine expression levels of Ang-2 and Tie2 were significantly elevated in HSP and pSLE patients, whereas the Ang-1/Ang-2 values were reduced. Additionally, Ang-1 was highly expressed in the serum and urine of HSP patients and in the serum of pSLE patients. Ang-1, Ang-2, and Tie2 showed differential expression in various types of HSP and pSLE compared with their expression in healthy controls. In summary, Ang-1, Ang-2, and Tie2 can serve as biomarkers for HSP and pSLE. Moreover, Ang-1/Ang-2 values are reduced in HSP and pSLE patients. Ang-1, Ang-2, and Tie2 can be used as biomarkers for HSP and pSLE.

Serum Angiopoietin-2 Levels Predict the Development of Hepatocellular Carcinoma following Hepatitis C Virus Eradication Using Direct-Acting Antiviral Agents

Plain Language SummaryOur previous studies showed that serum angiopoietin-2 (Ang-2) and C-X-C motif chemokine ligand 10 (CXCL10) levels predicted improvement in liver fibrosis following sustained virological response (SVR) of hepatitis C virus (HCV) obtained with administration of with direct-acting antiviral agents (DAAs). These levels were evaluated retrospectively as predictive indicators of hepatocellular carcinoma (HCC) development following SVR. We enrolled individuals from a historical cohort of 89 chronic HCV patients without history of HCC at baseline with SVR following DAA therapy and had baseline serum levels of Mac-2 binding protein glycosylation isomer ≥2.0 C.O.I. Multivariate analyses of patients revealed that only the Ang-2 level at 24 weeks following the end of treatment (EOT24W) was significantly related to HCC development (hazard ratio 2.27; p = 0.003). This result was reproduced in individuals with advanced liver fibrosis (M2BPGi level ≥3.3 C.O.I. at baseline). Time-dependent receiver operating characteristic curve analyses for the future risk of developing HCC within 5 years of follow-up (5y-HCC) showed the best cut-off Ang-2 level at EOT24W was 2,780 pg/mL, and significantly stratified the cumulative incidence of HCC (≥2,780 vs. < 2,780 pg/mL, 5y-HCC: 45.5 vs. 8.2%, p < 0.001). The serum Ang-2 level at EOT24W is a feasible predictor of HCC development after achieving SVR to DAAs therapy.

Maternal serum angiopoietins levels in pre-eclampsia and pregnancy outcomes.

Although the understanding of pre-eclampsia (PE) has improved, there is still insufficient knowledge on the exact etiology and pathophysiological mechanisms. Dysregulation of angiogenic factors has emerged as a significant contributing factor. Among these factors, angiopoietins (Ang-1 and Ang-2) have gained considerable attention due to their crucial role in regulating vascular development and endothelial function. This study explored the maternal serum levels of angiopoietins and perinatal outcomes in PE. A case-control study involving women with PE (cases) and normotensive pregnancies (controls) was conducted at the Maternity unit of the Korle-Bu Teaching Hospital. Descriptive analysis was performed and the Mann-Whitney U test (two-sided) was used to compare maternal serum levels of angiopoietins between the cases and controls. We included 188 participants comprising 94 cases (women with PE) and 94 controls (normotensive pregnancies) with an average maternal age of 29.76 ± 5.56 and 28.43 ± 5.57 years, respectively. Maternal serum levels of Ang-2 were significantly lower among the PE cases comparedto the normotensive controls (1.25 [0.90, 2.15] vs. 2.14 [1.18, 5.73] ng/mL, p = 0.001) but no significant difference in Ang-1 levels (92.61 [80.92, 114.92] vs. 99.26 [81.76, 113.12] ng/mL, p = 0.429) was observed between the groups. The Ang-1/Ang-2 ratio was significantly elevated among women with PE compared to normotensive controls (74.47 [37.69, 110.59] vs. 45.98 [16.11, 88.22] ng/mL, p = 0.014). Also, women who delivered vaginally had significantly high maternal serum levels of Ang-1 compared to women who had cesarean section delivery (107.98 ± 27.79 vs. 89.02 ± 32.62 ng/mL). Maternal serum levels of Ang-2 but not Ang-1 were significantly depressed in women with PE compared to the pregnant normotensive controls. No significant associations were observed between Ang-1, Ang-2 levels, or the Ang-1/Ang-2 ratio and pregnancy outcomes such as preterm birth, birth weight, and severity of hypertension.

Type I Interferons induce endothelial destabilization in Systemic Lupus Erythematosus in a Tie2-dependent manner.

Endothelial cell (EC) dysfunction is a hallmark of Systemic Lupus Erythematosus (SLE) and Tie2 is a receptor essential for vascular stability. Inflammatory processes promote inhibition of Tie2 homeostatic activation, driving vascular dysfunction. In this work we determined whether type I Interferons (IFN) induce Tie2 signalling-mediated endothelial dysfunction in patients with SLE. Serum levels of Angiopoietin (Ang)-1, Ang-2 and soluble (s)Tie1 in patients with SLE and healthy controls were measured by ELISA. Monocytes from patients with SLE and Human Umbilical Vein EC (HUVEC) were stimulated with IFN-α, IFN-β (1000 I.U.) or SLE serum (20%). mRNA and protein expression, phosphorylation and translocation were determined by quantitative PCR, ELISA, Western Blot, flow cytometry and confocal microscopy. Viability and angiogenic capacity were determined by calcein and tube formation assays. We found that sTie1 and Ang-2 serum levels were increased and Ang-1 decreased in patients with SLE and were associated with clinical characteristics. Type I IFN significantly decreased Ang-1 and increased Ang-2 in monocytes from patients with SLE. Type I IFN increased sTie1 and Ang-2 secretion and reduced Tie2 activation in HUVEC. Functionally, type I IFN significantly reduced EC viability and impaired angiogenesis in a Tie2 signalling-dependent manner. Finally, SLE serum increased Ang-2 and sTie1 secretion and significantly decreased tube formation. Importantly, Tie1 and IFNAR1 knockdown reversed these effects in tube formation. Overall, type I IFN play an important role in the stability of EC by inhibiting Tie2 signalling, suggesting that these processes may be implicated in the cardiovascular events observed in patients with SLE.

Serum Angiopoietin-2 level increase differs between polytraumatized patients with and without central nervous system injuries

Since endothelial cells rapidly release Angiopoietin-2 (Ang-2) in response to vascular injury and inflammatory stimuli, we aimed to investigate if its serum levels increase in polytraumatized patients. Our cohort study evaluated 28 blunt polytrauma survivors (mean age, 38.4 years; median ISS, 34) who were directly admitted to our level I trauma center in 2018. We assessed the serum Ang-2 level at admission and on days 1, 3, 5, 7, and 10 during hospitalization. Ang-2 was released into the circulation immediately after polytrauma. At admission (day 0), it amounted to 8286 ± 5068 pg/mL, three-and-a-half times the reference value of 2337 ± 650 pg/mL assessed in a healthy control group. Subgroup analysis provided a higher mean Ang-2 level in the CNSI group combining all patients suffering a brain or spinal cord injury compared to the non-CNSI group solely on day 0 [11083 ± 5408 pg/mL versus 3963 ± 2062 pg/mL; p < 0.001]. Whereas the mean Ang-2 level increased only in the non-CNSI group from day 0 to day 3 (p = 0.009), the respective curves showed similar continuous decreases starting with day 3. Multivariate logistic regression analysis revealed an association between the Ang-2 day 0 level and the presence of a CNSI (OR = 1.885; p = 0.048). ROC analysis provided a cutoff level of 5352 pg/mL. In our study group, serum Ang-2 levels assessed at admission differed between polytraumatized patients with and without brain or spinal cord injuries. Based on our findings, we consider serum Ang-2 levels an effective biomarker candidate for indicating CNSI in these patients at admission, worthy of further evaluation in large multicenter studies.

Preoperative Serum Levels of PDGF-AB, PDGF-BB, TGF-α, EGF and ANG-2 in the Diagnosis of Endometrial Cancer.

(1) Background: It is relevant to find new diagnostic biomarkers for endometrial cancer. This study aimed to investigate whether PDGF-AB, PDGF-BB, TGF-α, EGF and ANG-2 could be considered new useful markers for diagnosis and survival of endometrial cancer. (2) Methods: A total of 93 women diagnosed with endometrial cancer (EC) and 66 patients with non-cancerous endometrial lesions (NCEL) were included in this study. (3) Results: Median serum levels of PDGF-AB, PDGF-BB, TGF-α, EGF and ANG-2 were significantly higher in the EC group compared to the NCEL group (for PDGF-AB, PDGF-BB, TGF-α and ANG-2, p = 0.0000; for EGF, p = 0.0186). The cut-off level of PDGF-AB was set at 127.69 pg/mL with a sensitivity of 87.1% and a specificity of 66.67% (AUC = 0.78, p < 0.000001). The cut-off level of PDGF-BB was set at 207.86 ng/L with a sensitivity of 82.8% and a specificity of 75.76% (AUC = 0.85, p < 0.000001). The cut-off level of TGF-α was set at 33.85 ng/L with a sensitivity of 82.8% and a specificity of 75.76% (AUC = 0.82, p < 0.000001). The cut-off level of EGF was set at 934.76 pg/mL with a sensitivity of 83.87% and a specificity of 28.79% (AUC = 0.61, p = 0.018472). The cut-off level of ANG-2 was set at 3120.68 pg/mL with a sensitivity of 72.04% and a specificity of 93.94% (AUC = 0.87, p < 0.000001). (4) Conlusion: It was concluded that all the proteins studied could be potential diagnostic markers in endometrial cancer.

Angiopoietin-2 as a Predictor of Fibrosis Regression in Hepatitis C Virus-Patients after Direct Acting Antiviral Drugs

Abstract Background Hepatitis C virus (HCV) infection is the major cause of liver cirrhosis and hepatocellular carcinoma (HCC); thus, effective and safe treatment is crucial. Aim of the Work to evaluate the serum angiopoietin-2 as non-invasive marker of fibrosis regression in patients with Hepatitis C Virus receiving DAA drugs. Patients and Methods This study was conducted on 40 chronic HCV-patients who received DAA therapy in the Hepatic Virology Unit and the gastroenterology department of Ain Shams University hospitals. All patients were subjected to the following: Full history taking with stress concerning the hepatology system, clinical evaluation, laboratory investigations, Routine investigations: Abdominal and Pelvic ultrasonography and Transient elastography (Fibroscan) to measure liver stiffness measurement (LSM) for detection the degree of liver fibrosis in the chronic HCV-patients. Results Hematological findings, biochemical liver profile and liver fibrosis indices except hemoglobin level and platelets counts were significantly improved after DAA therapy. There was a significant improvement concerning the fibrosis stage after the treatment fibrosis staging at SVR12. The liver size, the spleen size and portal vein diameter were also significant after DAA therapy. There was improvement in the Child-Pugh score after successful HCV eradication by DAAs but the difference was no statistically significant. There was a statistically significant higher mean of Ang-2 levels in higher stages of liver fibrosis stages. Overall, serum Ang-2 levels significantly decrease after DAA therapy. In F0, F1, F2 &amp; F3 fibrosis stage; the mean Ang2 levels decrease after DAA therapy but in F4 fibrosis stage; the mean Ang2 levels did not change almost. Baseline Ang-2 and WBCs, AST, ALT, total bilirubin, INR, serum albumin, alpha-fetoprotein, serum creatinine, LSM, FIB-4 index, APRI score, liver size and portal vein diameter were significantly correlated. There were also a significant correlation between Ang-2 and all the fibrosis stages (from F0 to F4) before DAA treatment. Ang-2 levels were significantly associated with LSM based liver fibrosis stage regression after successful DAA therapy. Ang-2 levels did not correlate with hemoglobin, platelets and spleen size at baseline. Ang-2 levels did not correlate with hemoglobin, platelets, WBCs, INR, spleen size and portal vein diameter after DAA therapy. Ang-2 levels did not show significant correlation with the Child-Pugh score after DAA therapy. Conclusion Liver fibrosis stage after successful HCV eradication by DAAs. But in stage F4 (cirrhosis), mean Ang-2 remained almost unchanged after DAA therapy. Significant decrease of Serum Ang-2 could suggest its use as a predictor of liver fibrosis regression in Hepatitis C Virus-patients after Direct Acting Antiviral drugs after DAA therapy.

Endothelial Injury Syndromes after Allogeneic Hematopoietic Stem Cell Transplantation: Angiopetin-2 as a Novel Predictor of the Outcome and the Role of Functional Autoantibodies against Angiotensin II Type 1 and Endothelin A Receptor.

Transplant-associated thrombotic microangiopathy (TMA) occurs in a significant percentage of patients after allogeneic stem cell transplantation (allo-SCT) and is associated with significant morbidity and mortality. The aim of the present study was to examine the association of serum angiopoetin-2 (Ang2) levels and the presence of antibodies against angiotensin II type 1 (AT1R) and ndothelin A Recreptor (ETAR) with the outcome of patients with TMA and/or graft-versus-host disease (GVHD) after allo-SCT. Analysis of our data showed that elevated serum Ang2 levels at the time of TMA diagnosis are significantly associated with increased non-relapse mortality and decreased overall survival. To our knowledge, this is the first study demonstrating an association between raised Ang2 levels and poor outcomes in patients with TMA. Antibodies against AT1R (AT1R-Abs) and ETAR (ETAR-Abs) were detected in 27% and 23% of the patients, respectively, but there was no association between the presence of autoantibodies and the outcome of patients with TMA. However, a significant finding was the strong positive correlation between the presence of AT1R-Abs with the occurrence of chronic fibrotic GVHD, such as scleroderma and cryptogenic organizing pneumonia, raising the possibility of the contribution of autoantibodies in the pathogenesis of fibrotic GVHD manifestations.

Changes in Serum Growth Factors during Resistance to Atezolizumab Plus Bevacizumab Treatment in Patients with Unresectable Hepatocellular Carcinoma.

The possible mechanisms of resistance to atezolizumab/bevacizumab for unresectable HCC, and the subsequent response to these therapies, remain underexplored. The sequential changes in serum growth factors, including VEGF-A, VEGF-C, VEGF-D, ANG-2, FGF-19, HGF, and EGF during atezolizumab/bevacizumab for unresectable HCC were evaluated in 46 patients. Patients who experienced PD after CR, PR, or SD to atezolizumab/bevacizumab were evaluated. A total of 4, 9, 19, and 14 patients showed CR, PR, SD, and PD, respectively. Of 32 patients with disease control, 28 experienced PD after CR, PR, or SD with atezolizumab/bevacizumab. Baseline growth factor levels were similar between patients with or without disease control and those with or without an objective response. Growth factor changes between the baseline and the best overall response points (BOR) for patients with disease control showed that FGF-19 significantly increased and ANG2 significantly decreased at the BOR. Growth factor changes between the BOR and the PD point in 28 patients who experienced PD after disease control showed that VEGF-D and ANG2 significantly increased at the PD point compared with that at the BOR. Summarily, increased serum VEGF-D and ANG-2 levels might contribute to developing resistance to atezolizumab/bevacizumab for unresectable HCC and might be target molecules in subsequent salvage therapies.

Serum Angiopoietin-2 Predicts the Occurrence and Recurrence of Hepatocellular Carcinoma after Direct-Acting Antiviral Therapy for Hepatitis C.

Progressive liver fibrosis after anti-HCV treatment is a risk factor for HCC. Angiopoietin-2 (Ang2) is associated with non-regression of liver fibrosis after direct-acting antiviral (DAA). This study evaluated the predictive value of serum Ang2 levels for HCC occurrence or recurrence after DAA administration. In this retrospective study, 310 HCV-infected patients treated with DAAs in 2014-2020 were screened and evaluated for HCC occurrence or recurrence every three-six months. Multivariate Cox regression analysis revealed that age ≥ 75 years (HR: 2.92, 95% CI: 1.34-6.33; p = 0.007) and baseline Ang2 level ≥ 464 pg/mL (HR: 2.75, 95% CI: 1.18-6.37; p = 0.019) were significantly associated with HCC occurrence after DAA therapy. A high or low risk of HCC after DAA therapy could be distinguished by the combination of age and baseline Ang2 level. The cumulative incidences of de-novo HCC at two and four years were 0.8% and 3.8% in the low-risk group and 22.6% and 27.1% in the high-risk group, respectively. Baseline Ang2 level ≥ 402 pg/mL was significantly associated with HCC recurrence in patients who achieved sustained virological response with DAAs (HR: 3.68). In conclusion, serum Ang2 levels can predict HCC occurrence and recurrence after successful HCV eradication by DAAs.

Baseline Ang-2 Serum Levels as a Predictive Factor for Survival in NSCLC and SCLC.

Angiopoietin-2 (Ang-2) has been implicated in the development of several types of cancer, including lung malignancy. In the present study, we examined the impact of Ang-2 serum concentration on the development, dissemination, and 5-year overall survival of NSCLC and SCLC. A total of 99 patients with lung cancer were tested. The OS of NSCLC and SCLC patients was estimated using Kaplan−Meier curves and compared through log-rank test. The median serum level of Ang-2 at baseline in both NSCLC and SCLC patients was significantly higher than that of controls (p < 0.0001). The Ang-2 serum concentration was not related to metastasis, neither in NSCLC nor in SCLC cases. The OS was found to be significantly shorter for stage IIIβ NSCLC patients with a high baseline Ang-2 serum concentration (p = 0.012), while Cox regression analysis showed that Ang-2 is a significant independent factor for poor prognosis for stage IIIβ NSCLC (hazard ratio = 2.97, 95% CI: 1.05−8.40, p = 0.04). The concentration of Ang-2 has no impact on the prognosis of SCLC. Ang-2 could be considered as a significant molecular marker that enables the prediction of NSCLC and SCLC development, and is involved in the poor prognosis of stage IIIβ NSCLC.

Enhanced external counterpulsation ameliorates endothelial dysfunction and elevates exercise tolerance in patients with coronary artery disease.

Enhanced external counterpulsation (EECP) is a new non-drug treatment for coronary artery disease (CAD). However, the long-term effect of EECP on endothelial dysfunction and exercise tolerance, and the relationship between the changes in the endothelial dysfunction and exercise tolerance in the patients with coronary heart disease are still unclear. A total of 240 patients with CAD were randomly divided into EECP group (n = 120) and control group (n = 120). All patients received routine treatment of CAD as the basic therapy. Patients in the EECP group received 35 1-h daily sessions of EECP during 7 consecutive weeks while the control group received the same treatment course, but the cuff inflation pressure was 0-10 mmHg. Peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI), and inner diameter (ID) of the right carotid artery were examined using a Color Doppler Ultrasound and used to calculate the fluid shear stress (FSS). Serum levels of human vascular endothelial cell growth factor (VEGF), vascular endothelial cell growth factor receptor 2 (VEGFR2), and human angiotensin 2 (Ang2) were determined by enzyme-linked immunosorbent assay (ELISA). Exercise load time, maximal oxygen uptake (VO2max ), metabolic equivalent (METs), anaerobic threshold (AT), peak oxygen pulse (VO2max/HR) were assessed using cardiopulmonary exercise tests. After 1 year follow-up, the EDV, PSV, ID, and FSS were significantly increased in the EECP group (P < 0.05 and 0.01, respectively), whereas there were no significant changes in these parameters in the control group. The serum levels of VEGF and VEGFR2 were elevated in the EECP and control groups (all P < 0.05). However, the changes in VEGF and VEGFR2 were significantly higher in the EECP group than in the control group (P < 0.01). The serum level of Ang2 was decreased in the EECP group (P < 0.05) and no obvious changes in the control group. As for exercise tolerance of patients, there were significant increases in the exercise load time, VO2max, VO2max/HR, AT and METs in the EECP group (all P < 0.05) and VO2max and METs in the control group (all P < 0.05). Correlation analyses showed a significant and positive correlations of VEGF and VEGFR2 levels with the changes in FSS (all P < 0.001). The correlations were still remained even after adjustment for confounders (all Padjustment < 0.001). Linear regression displays the age, the medication of ACEI (angiotensin-converting enzyme inhibitors) or ARB (angiotensin receptor blockers), the diabetes and the changes in VEGF and VEGFR2 were positively and independently associated with the changes in METs after adjustment for confounders (all Padjustment < 0.05). The data of our study suggested that EECP is a useful therapeutic measurement for amelioration of endothelial dysfunction and long-term elevation of exercise tolerance for patients with coronary heart disease. [http://www.chictr.org.cn/], identifier [ChiCTR1800020102].

Value of Serum miR-34a and Ang-1 in Severity Evaluation and Prognosis of Neonatal Respiratory Distress Syndrome.

Methods A total of 96 neonates with RDS admitted to the hospital from February 2020 to April 2021 were selected as the research subjects. According to the neonatal critical illness score, the subjects were divided into non-critical group (n = 50), critical group (n = 27), and extremely critical group (n = 19). According to survival status, the subjects were divided into survival group (n = 76) and death group (n = 20). Serum miR-34a and Ang-1 levels and NCIS were compared between RDS neonates with different severity and prognosis. The predictive value of serum miR-34a, Ang-1, and NCIS for death was analyzed using the receiver operating characteristic (ROC) curve. Results Serum miR-34a and Ang-1 levels and NCIS were significantly different in the 3 groups (P < 0.05). Serum miR-34a level decreased in order, while serum Ang-1 level and NCIS increased in order from the extremely critical group, the critical group to the non-critical group (P < 0.05). The survival group had lower serum miR-34a level and higher Ang-1 level and NCIS than the death group (P < 0.05). ROC curve analysis showed that the area under the curve (AUC) values of serum miR-34a, Ang-1, and NCIS to predict death of RDS neonates were 0.745, 0.7667, and 0.736. The cutoff values were 1.175, 6.815 ng/mL, and 85 points. The AUC of joint prediction with the three was 0.924, significantly larger than that of each index. The sensitivity and specificity were 94.70% and 90.00%. Conclusion Serum miR-34a, Ang-1, and NCIS are closely related to the severity and prognosis of neonatal RDS. Combined detection of the three is helpful for prognosis of neonatal RDS.

Serum angiopoietin-2 levels predict regression of Mac-2 binding protein glycosylation isomer-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents.

It is desirable to identify predictors of regression of liver fibrosis after achieving a sustained virologic response (SVR) by direct-acting antiviral agents (DAAs) to antihepatitis C virus (HCV) therapy. Here, we retrospectively investigated the serum angiopoietin-2 (Ang-2) level as a predictive indicator of regression of liver fibrosis after successful HCV eradication by DAA therapy. The study subjects were recruited from a historical cohort of 109 chronically HCV-infected patients who had achieved SVR by DAA therapy and whose serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels at baseline (before DAA therapy) were ≥2.0 the cut-off index (COI). We defined patients with M2BPGi levels <1.76 and≥1.76 COI at 2years after the end of treatment (EOT) as the regression (R, n=69) and nonregression (NR, n=40) groups, respectively. Multivariate analyses revealed that the Ang-2 level at baseline and the Ang-2 level, albumin-bilirubin score, and FIB-4 index at 24weeks after the EOT were significantly associated with regression of M2BPGi-based liver fibrosis. Receiver operating characteristic curve analyses showed that the Ang-2 level at 24weeks after the EOT had the largest area under the curve values (0.859). The same results were obtained even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis: M2BPGi levels ≥3.3 COI at baseline. The serum Ang-2 level at 24weeks after the EOT is a feasible predictor of regression of M2BPGi-based liver fibrosis after achieving SVR by DAA therapy.

Effect of modified Wenyang Buxin decoction and routine therapy on cardiac function and serum levels of H-FABP, cTnI and Ang-2 in chronic heart failure patients

Purpose: To investigate the effect of modified Wenyang Buxin decoction and routine therapy on cardiac function and serum levels of heart-type fatty acid binding protein (H-FABP), cardiac troponin-1 (cTnI) and angiopoietin-2 (Ang-2) in chronic heart failure (CHF) patients.Methods: A total of 120 CHF patients admitted to Zhejiang Province Rongjun Hospital (from January2019 - January 2020) were selected for this study. They were randomly but equally distributed into groups A and B. All patients were given routine therapy such as diuretic treatment and detumescence, while those in group A received 150 mL of modified Wenyang Buxin decoction daily, in addition to routine therapy. At 2 months after therapy, cardiac function indices, serum H-FABP, cTnI and Ang-2 levels, hemorheology indices, traditional Chinese medicine (TCM) syndrome scores, and Chinese questionnaire of quality of life in cardiovascular patients (CQQC) scores of the two groups were evaluated.Results: After therapy, cardiac function indices, serum H-FABP, cTnI and Ang-2 levels, hemorheology indices as well as TCM syndrome score and CQQC score were significantly improved in group A, when compared with corresponding values in group B (p &lt; 0.05).Conclusion: Modified Wenyang Buxin decoction and routine therapy improves serum biomarker levels, cardiac function and quality of life, and relieves clinical symptoms of CHF in patients. Therefore, this treatment approach may be useful in the management of CHF patients.

Biomarkers of endothelial dysfunction and atherosclerosis in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with an increased prevalence of subclinical atherosclerosis and cardiovascular risk. Angiopoietin-2 (Ang-2), asymmetric dimethylarginine (ADMA), and osteoprotegerin (OPG) are molecules related to endothelial dysfunction (ED) and atherosclerosis, but also to disease severity in patients with chronic inflammatory disorders. In this case-control study, we aimed to investigate serum Ang-2, ADMA, and OPG levels in patients with HS, and to assess the potential relationship between these levels and disease severity. Seventy-five patients with HS and 60 controls were assessed. Serum Ang-2, ADMA, and OPG concentrations were determined in all participants. HS patients had significantly higher Ang-2 and ADMA levels than controls after adjusting for confounders. Besides, Ang-2 concentrations positively correlated with disease severity in the adjusted multivariable analysis. Nevertheless, serum OPG levels did not significantly differ between HS patients and controls. Our results indicate that serum Ang-2 and ADMA levels are significantly increased in patients with HS. Furthermore, Ang-2 might be a suitable marker of HS severity.

Are programmed cell death protein-1 and Angiopoietins-2 effective biomarkers for detection the severity of psoriatic patients?

Early detection of psoriasis is still an open discussion. Psoriatic lesions are characterized by red/scaly plaques affecting different body-sites. To evaluate the levels of programmed cell death protein-1(PD-1) and Angiopoietins-2(Ang-2) in serum, lesional, and perilesional of psoriatic patients and correlate them with controls and disease severity. Serum samples were obtained from 40 participants subdivided equally into psoriatic and healthy controls, 4 mm punch_biopsy equally from lesional and perilesional skin of individuals. PD-1/ANG-2 ELISA kits were used for determining the serum and tissue levels among groups. Serum and tissue levels of PD-1 and Ang-2 were overexpressed in psoriatic patients compared with controls. There was a statistical difference between patients and controls in level of PD-1(serum and tissue) with p-value 0.006 and 0.0001, respectively. There was a statistical difference between both groups for ANG-2(serum and tissue) with p-value 0.03 and 0.0001, respectively. There were positive correlations between PASI score and PD-1 in tissue (r = 0.467, p = 0.038). Also, positive correlation between the level of PD-1 in serum and tissue (r = 0.369, p = 0.019), the serum levels of PD-1 and ANG-2 (r = 0.78, p > 0.0001), PD-1 and Ang-2 in tissue (r = 0.583,p = 0.0001) were detected. PD-1 and ANG-2 can be highly recommended to determine the severity of psoriasis.

Clinical significance of differential serum-signatures for early prediction of severe dengue among Eastern Indian patients.

Dengue infection can result in simple dengue fever or life-threatening severe dengue. Early identification of severe patients is needed for proper disease management. Dengue infection was screened among 168 symptomatic patients by qRT-PCR, anti-dengue IgM, and IgG ELISA. Dengue patients were categorized according to WHO classification. Viral load and dengue serotypes were determined by qRT-PCR. Levels of acute-phase-proteins (SAP, SAA2; CRP and ApoA1), endothelial (Ang2, VEGF), coagulation (fibrinogen) markers were determined by sandwich ELISA/immunoturbidimetry/western-blotting. Hepatic (ALT, AST, ALP) and other blood biochemical parameters were studied by autoanalyzer and haematology cell counter. Statistical analysis and protein-protein-interaction network were performed by GraphPad-Prism and STRINGS database, respectively. Among 87 dengue patients, significantly higher levels of Ang2, VEGF, CRP, SAA2, ApoA1, AST, ALT, and AST/ALT ratio and low level of fibrinogen were detected in severe-dengue cases compared to dengue without warning-signs, with seven of them severely altered during febrile-phase. Higher fold-change of Ang2 and VEGF as well as decreased fibrinogen were observed among patients with haemorrhagic-manifestation, clinical-fluid accumulation and thrombocytopenia. Functional network analysis predicted Ang2, VEGF, and CRP to be functionally and physically connected and SAA2 and ApoA1 to be functioning together. Correlation analyses also validated this connectivity by a strong positive correlation between Ang2, VEGF, and CRP. PCA analysis followed by hierarchical clustering heatmap analysis segregated severe-dengue patients from the rest, with VEGF, Ang2, ApoA1, AST, and ALT clearly distinguishing the severe-dengue group. Thus, serum levels of VEGF, Ang2, ApoA1, AST, and ALT might act as potential biomarkers for predicting dengue severity during the early stage.

Angiogenic factors as prognostic markers in neuroendocrine neoplasms

Angiogenic markers in neuroendocrine neoplasms (NENs) have recently received increasing attention, but their clinical role remains unclear. The aim of this study was to evaluate the role of angiogenic markers in NEN aggressiveness and prognosis. We performed a prospective observational study including 46 consecutive patients with proven NENs of pulmonary (45.65%) and gastro-entero-pancreatic (GEP) (54.35%) origin and 29 healthy controls. Circulating pro-angiogenic factors were measured by ELISA assay. ANG2 tissue expression was evaluated in a subgroup of ten patients by immunohistochemistry. The study demonstrated a significantly higher level of ANG2, ANG1, sTIE2, and PROK2 in patients affected by NENs compared to controls. In the NENs' group we measured that: (i) ANG2 levels were higher in poorly vs well-differentiated NENs: 4.85 (2.75-7.42) vs 3.16 (1.66-6.36) ng/ml, p = 0.046 and in tumor stage 3-4 compared to stage 1-2: 4.24 (2.66-8.72) vs 2.73 (1.53-5.70), p = 0.044; (ii) ANG2 and PROK2 were significantly higher in patents with progressive disease compared to stable disease: ANG2 = 6.26 (3.98-10.99) vs 2.73 (1.65-4.36) pg/ml, p = 0.001; PROK2 = 29.19 (28.42-32.25) vs 28.37 (28.14-28.91) pg/ml, p = 0.035. Immunohistochemistry confirmed ANG2 expression in tumor specimens. We documented higher levels of angiogenic markers in NENs, with an association between ANG2 serum levels and NENs morphology and staging. In both GEP and lung NENs, ANG2 and PROK2 are higher in case of tumor progression, suggesting a potential role as prognostic markers in NENs patients.

DYNAMICS OF FIBROTIC CHANGES IN THE LIVER AFTER THE SUCCESSFUL ERADICATION OF HEPATITIS C VIRUS IN PATIENTS WITH NAFLD.

The aim: To assess the dynamics of serum levels of angiopoietin-2 and transforming growth factor-β1 in patients with chronic hepatitis C (CHC) with concomitant nonalcoholic fatty liver disease (NAFLD) after successful DAAs. Materials and methods: 82 patients with CHC were examined, of which 56 were diagnosed with NAFLD and increased body weight. Ang-2, TGF-β1, leptin, adiponectin, and the degree of liver fibrosis were determined for all participants. The patients were divided into groups: 1 gr. (n=23) - CHС + increased body weight + hepatic steatosis, 2 gr. (n=33) - СНС + increased body weight + nonalcoholic steatohepatitis, 3rd gr. (n=26) - CHC. All patients received DAAs for 12 weeks. Results: From 82 patients F3-4 had 31 people, F1-2 - 25, F0-1 - 11, F0 -15 patients. F3-4 and steatosis S2-3 (p<0.05) was more common in patients of 2 gr.. Serum Ang-2 levels were higher (p<0.05) in patients of 2 gr. with F3-4, than in patients with F0-2. Fibrosis regression occurred more often in patients with 1 and 3 gr. with F1-2 than in patients 2 gr. and F3-4 and was accompanied by a decrease in Ang-2 and TGF-β1 levels. Conclusions: High levels of Ang-2 and TGF-β1 are registered in patients with CHC+NAFLD, which correlate with the degree of liver fibrosis and significantly decrease after successful DAAs in patients with low initial stages of liver fibrosis and normal body weight.