Serum Angiopoietin-like Protein Research Articles

Predictive Value of Lung Ultrasound Scores Combined with Serum ANGPTL4 Levels on Severity and Prognosis of Neonatal Respiratory Distress Syndrome.

Respiratory distress syndrome threatens neonates' life. This study probed the predictive value of lung ultrasound scores combined with serum angiopoietin-like protein 4 (ANGPTL4) levels on neonatal respiratory distress syndrome (NRDS) severity and prognosis. The NRDS group (n = 115) and control group (n = 30) were established. In both groups, lung ultrasound scores and serum ANGPTL4 levels, lung ultrasound scores and serum ANGPTL4 levels of newborns with NRDS of different severity, the risk factors affecting the poor prognosis of NRDS neonates, and the value of serum ANGPTL4 levels combined with lung ultrasound scores in determining the severity and prognosis of newborns with NRDS were analyzed. The NRDS groups had higher lung ultrasound scores and serum ANGPTL4 levels, and lower Apgar scores than the control group; lung ultrasound scores and serum ANGPTL4 levels were higher in the moderate and severe groups than in the mild group, and those were higher in the severe group than in the moderate group (all p < 0.05). The logistic regression analysis showed that high lung ultrasound scores, and high serum ANGPTL4 levels were risk factors for NRDS poor prognosis (OR > 1, p < 0.05), and high Apgar scores are the protective factor for poor prognosis in NRDS neonates (OR < 1, p < 0.05). The area under the curve of lung ultrasound scores combined with serum ANGPTL4 levels to assess the severity and prognosis of NRDS neonates exhibited a higher assessed value than the single test. Lung ultrasound scores and serum ANGPTL4 levels are closely related to the severity and prognosis of NRDS neonates, and the combination of the two improves the assessed value of the severity and prognosis of NRDS neonates. The study provided a reference for the disease severity assessment of NRDS and the prediction of its prognosis.

Prognostic value of serum angiopoietin-like protein 2 in patients with acute coronary syndrome

BackgroundAngiopoietin-like protein 2 (Angptl2) is a cytokine that is released to stimulate inflammation and accelerate atherogenesis. Our study sought to assess the predictive significance of serum Angptl2 in individuals diagnosed with acute coronary syndrome (ACS) and determine whether it can enhance prognostic performance beyond the GRACE risk score.MethodsWe recruited a total of 1060 patients with ACS in a consecutive manner. The levels of Angptl2 in serum were analyzed at baseline. The subjects were then followed up for 12 months to monitor the occurrence of major adverse cardiovascular events (MACE).ResultsThe level of serum Angptl2 showed a positive correlation with the GRACE score (r = 0.54, p < 0.001). Survival analysis revealed that increased levels of serum Angptl2 were associated with higher occurrence of the composite of MACE (log-rank p < 0.001) and its specific components (log-rank p = 0.011 for all-cause death, p = 0.007 for non-fatal myocardial infarction and p < 0.001 for revascularization respectively). Throughout the follow-up period, 163 instances (15.4%) of endpoint events were documented. In terms of MACE, both serum Angptl2 levels (HR: 1.178, 95% CI: 1.058–1.313, p = 0.003) and the GRACE risk score (HR: 1.181, 95% CI: 1.007–1.385, p = 0.041) emerged as significant predictors following Cox multivariate adjustment. Additionally, the addition of serum Angptl2 to the GRACE score improved the predictive capacity for prognosis [increase in area under the receiveroperating characteristic curve (AUC) from 0.740 to 0.794, p = 0.020; net reclassification improvement (NRI) = 0.401, p = 0.001; integrated discrimination improvement (IDI) = 0.022, p = 0.008].ConclusionSerum Angptl2 might be a useful prognostic biomarker and combining serum Angptl2 with the GRACE score increased the efficacy of prognosis prediction in ACS patients.Trial registrationNot applicable.

Correlation between serum ANGPTL4 levels and white matter hyperintensity and cognitive impairment in patients with cerebral small vessel disease.

To investigate the correlation between serum angiopoietin-like protein 4 (ANGPTL4) levels, white matter hyperintensity (WMH), and cognitive impairment (CI) in patients with cerebral small vessel disease (CSVD). This cross-sectional study enrolled 171 patients with CSVD who attended the First Affiliated Hospital of Xinxiang Medical University from December 2021 to July 2022. All subjects underwent a 3.0T head magnetic resonance imaging, neuropsychology assessment, and blood sampling. Serum ANGPTL4 levels were detected by enzyme-linked immunosorbent assay and the severity of WMH was assessed by the Fazekas scale. According to the Montreal Cognitive Assessment (MoCA) scale, subjects were divided into normal cognition group (NC, n=80) and CI group (n=91). According to the total Fazekas scores, subjects were divided into a mild WMH group (n=84), a moderate WMH group (n=70), and a severe WMH group (n=17). Serum ANGPTL4 levels were significantly higher in the CI group than in the NC group (p<.05) and were negatively correlated with mini-mental state examination scores and MoCA scores (r=-0.26, -0.341, p<.05). Serum ANGPTL4 levels increased significantly in the mild to moderate WMH group but tended to decrease in the severe WMH group. Binary logistic regression analysis showed that ANGPTL4 was an independent influencing factor for CSVD-CI (OR=2.062, 95% CI (1.591-2.674), p<.001). The area under curve of ANGPTL4 for CSVD-CI was 0.847 (0.791-0.903). ANGPTL4 may be involved in the process of white matter damage and CI in CSVD patients and shows a diagnostic value for CSVD-CI.

Serum angiopoietin-like protein 2 level in patients who received bevacizumab-containing chemotherapy for metastatic colorectal cancer.

209 Background: Anti-angiogenic agents are important for treating patients with advanced colorectal adenocarcinoma, however, their efficacy is not long-lasting and survival benefits are modest. Reliable biomarkers and novel targets for angiogenesis are still required in this era. Angiopoietin-like protein 2 (AGLP-2) is an emerging biomarker for angiogenesis in cardiovascular disease, but its role in the oncology area is yet to be elucidated. Methods: Serum samples from patients with advanced colorectal carcinoma treated with bevacizumab-containing chemotherapy were retrospectively studied. Blood samples at baseline and at disease progression of the first line systemic therapy were selected. Serum angiopoietin-like protein 2 (AGLP-2) concentrations were measured using ELISA kit, serial changes, and the relationship with progression-free survival and overall survival on the systemic therapy were statistically analyzed. Results: 68 patients were enrolled. Their median age was 66 years old (range, 38-82), and 14 (20.6%) patients had metastatic lesions at 3 or 4 organs. The median serum AGLP-2 levels at baseline and at disease progression (PD) were 41,618 pg/ml (95% confidence interval (CI) 34,560-40,713), and 49,706 pg/ml (95% CI 39,853-49,017), respectively. There was a tendency of difference between AGLP-2 levels at baseline and at PD ( p=0.057). Patients whose baseline serum AGLP-2 levels with 40,000 pg/ml or above showed relatively shorter overall survival (median 31.4 months with 95% CI, 14.4-38.6) compared with patients with serum AGLP-2 level below 40,000 pg/ml at baseline (median 38.6 months with 95% CI, 23.6-127.3), but not statistically significant ( p=0.0946). There was no survival difference observed according to serum AGLP-2 levels at disease progression on the first line bevacizumab-containing chemotherapy. Conclusions: Serum angiopoietin-like protein-2 has potential as a new target for novel anti-angiogenic therapy in metastatic colorectal cancer.

Serum Angiopoietin-like Protein 3 Levels Are Associated with Endothelial Function in Patients with Maintenance Hemodialysis.

Angiopoietin-like protein 3 (ANGPTL3) plays an important role in lipid and lipoprotein trafficking and metabolism and is positively correlated with cardiovascular disease. Our objective was to evaluate the association between serum ANGPTL3 levels and endothelial function in patients on maintenance hemodialysis (MHD). We enrolled 116 patients on MHD and obtained their blood test results from their medical records. Using a noninvasive digital thermal monitor, we determined the vascular reactivity index (VRI) as a measure of endothelial function. Serum ANGPTL3 concentration was measured by a commercial-enzyme-linked immunosorbent assay. Vascular reactivity was classified as poor in 17 (14.7%) patients, intermediate (1.0 ≤ VRI < 2.0) in 50 (43.1%) patients, and high (VRI ≥ 2.0) in 49 (42.2%) patients. Serum levels of ANGPTL3 (p < 0.001) and alkaline phosphatase (ALP, p = 0.025) increased significantly as the VRI decreased. The log-transformed serum ALP (log-ALP, r = -0.187, p = 0.045) and log-ANGPTL3 (r = -0.319, p < 0.001) showed a negative correlation with the VRI on univariate linear regression analysis. A significant negative correlation was found between log-ANGPTL3 and VRI (p < 0.001) on multivariate stepwise linear regression analysis. The findings of our investigation showed that, in patients with MHD, the ANGPTL3 concentration had a negative correlation with the VRI.

The impact of gender on the relation of serum angiopoietin-like protein 8 (ANGPTL8) level with metabolic parameters in adults

The impact of gender on the relation of serum angiopoietin-like protein 8 (ANGPTL8) level with metabolic parameters in adults

Angiopoietin-like protein 8 deficiency attenuates thoracic aortic aneurysm/dissection development in β-aminopropionitrile monofumarate-induced model mice

Thoracic aortic aneurysm/dissection (TAAD) is a life-threatening cardiovascular disorder. Endoplasmic reticulum stress (ERS) and vascular smooth muscle cell (VSMC) apoptosis are involved in TAAD progression. The Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) pathway is associated with VSMC apoptosis. Serum Angiopoietin-Like Protein 8 (ANGPTL8) levels are associated with aortic diameter and rupture rate of TAAD. However, a direct role of ANGPTL8 in TAAD has not been determined. β-Aminopropionitrile monofumarate (BAPN) was used to induce TAAD in C57BL/6 mice. ANGPTL8 knockout mice were used to detect the effects of ANGPTL8 on TAAD development. ANGPTL8knockdown in vitro was used to analyze the role of ANGPTL8 in VSMCs and ERS. In addition, over-expression of ANGPTL8 in VSMCs and a PERK inhibitor were used to assess the effect of ANGPTL8 on the PERK pathway. ANGPTL8 levels were increased in the aortic wall and VSMCs of BAPN-induced TAAD mice. Compared with BAPN-treated wild-type mice, ANGPTL8 knockout significantly reduced the rupture rate of TAAD to 0 %. In addition, the protein levels of proinflammatory cytokines and matrix metalloproteinase 9 (MMP9) and ERS proteins were decreased in the aorta wall. Angptl8 shRNA decreased MMP9 and ERS protein levels in VSMCs in vitro. Overexpression of ANGPTL8 significantly increased the levels of ERS proteins and MMPs, while a PERK inhibitor significantly decreased the effects of ANGPTL8 in VSMCs. ANGPTL8 contributed to TAAD development by inducing ERS activation and degradation of extracellular matrix in the aorta wall. Inhibition of ANGPTL8 may therefore represent a new strategy for TAAD therapy.

ANGPTL8 promotes adipogenic differentiation of mesenchymal stem cells: potential role in ectopic lipid deposition.

BackgroundEctopic lipid deposition plays a promoting role in many chronic metabolic diseases. Abnormal adipogenic differentiation of mesenchymal stem cells (MSCs) is an important cause of lipid deposition in organs. Studies have shown that serum angiopoietin-like protein 8 (ANGPTL8) levels are increased in patients with many chronic metabolic diseases (such as type 2 diabetes, obesity, and hepatic steatosis), while the role of ANGPTL8 in ectopic lipid accumulation has not been reported.MethodsWe used the Gene Expression Omnibus (GEO) database to analyze the expression of ANGPTL8 in subcutaneous adipose tissue of obese patients and qPCR to analyze the expression of ANGPTL8 in the liver of high-fat diet (HFD)-induced obese mice. To explore the potential roles of ANGPTL8 in the progression of ectopic lipid deposition, ANGPTL8 knockout (KO) mice were constructed, and obesity models were induced by diet and ovariectomy (OVX). We analyzed lipid deposition (TG) in the liver, kidney, and heart tissues of different groups of mice by Oil Red O, Sudan black B staining, and the single reagent GPO-PAP method. We isolated and characterized MSCs to analyze the regulatory effect of ANGPTL8 on Wnt/β-Catenin, a key pathway in adipogenic differentiation. Finally, we used the pathway activator LiCl and a GSK3β inhibitor (i.e., CHIR99021) to analyze the regulatory mechanism of this pathway by ANGPTL8.ResultsANGPTL8 is highly expressed in the subcutaneous adipose tissue of obese patients and the liver of HFD-induced obese mice. Both normal chow diet (NCD)- and HFD-treated ANGPTL8 KO male mice gained significantly less weight than wild-type (WT) male mice and reduced ectopic lipid deposition in organs. However, the female mice of ANGPTL8 KO, especially the HFD group, did not show differences in body weight or ectopic lipid deposition because HFD could induce estrogen overexpression and then downregulate ANGPTL8 expression, thereby counteracting the reduction in HFD-induced ectopic lipid deposition by ANGPTL8 deletion, and this result was also further proven by the OVX model. Mechanistic studies demonstrated that ANGPTL8 could promote the differentiation of MSCs into adipocytes by inhibiting the Wnt/β-Catenin pathway and upregulating PPARγ and c/EBPα mRNA expression.ConclusionsANGPTL8 promotes the differentiation of MSCs into adipocytes, suggesting that ANGPTL8 may be a new target for the prevention and treatment of ectopic lipid deposition in males.

ANGPTL3 Is Involved in the Post-prandial Response in Triglyceride-Rich Lipoproteins and HDL Components in Patients With Coronary Artery Disease.

It is well-established that there exists an inverse relationship between high-density lipoprotein (HDL) cholesterol and triglyceride (TG) levels in the plasma. However, information is lacking on the impact of post-prandial triglyceride-rich lipoproteins (TRLs) on the structure of HDL subclasses in patients with coronary artery disease (CAD). In this study, the data of 49 patients with CAD were analyzed to evaluate dynamic alterations in post-prandial lipid profiles using nuclear magnetic resonance-based methods. An enzyme-linked immunosorbent assay was used to quantify the serum angiopoietin-like protein 3 (ANGPTL3). After glucose supplementation, the expression of hepatic ANGPTL3 was evaluated both in vitro and in vivo. Compared to fasting levels, the post-prandial serum TG level of all participants was considerably increased. Although post-prandial total cholesterol in HDL (HDL-C) remained unchanged, free cholesterol in HDL particles (HDL-FC) was significantly reduced after a meal. Furthermore, the post-prandial decrease in the HDL-FC level corresponded to the increase in remnant cholesterol (RC), indicating the possible exchange of free cholesterol between HDL and TRLs after a meal. Moreover, CAD patients with exaggerated TG response to diet, defined as TG increase >30%, tend to have a greater post-prandial increase of RC and decrease of HDL-FC compared to those with TG increase ≤30%. Mechanistically, the fasting and post-prandial serum ANGPTL3 levels were significantly lower in those with TG increase ≤30% than those with TG increase >30%, suggesting that ANGPTL3, the key lipolysis regulator, may be responsible for the different post-prandial responses of TG, RC, and HDL-FC.

Angiopoietin-Like Protein 4 May Be an Interplay Between Serum Uric Acid and Triglyceride-Rich Lipoprotein Cholesterol.

BackgroundAlthough the available evidence has indicated a link between elevated serum uric acid (SUA) level and dyslipidemia, the potential contribution of SUA on lipid profiles remains unclear. Experimental and clinical studies have revealed several mechanisms through which high serum angiopoietin-like protein 4 (ANGPTL4) level exerts deleterious effects on lipid metabolism, but the role of ANGPTL4 in SUA-associated dyslipidemia has not been well studied, so far.MethodsA total of 80 subjects were classified into high SUA group (n = 40) and low SUA group (n = 40) by the median value of SUA in the whole study population. Serum ANGPTL4 levels were determined by enzyme-linked immunosorbent assays.ResultsIn our study, we observed that not only serum triglyceride level [1.03 (0.78, 1.50) mmol/L vs. 1.59 (1.18, 2.37) mmol/L, p = 0.001] but also serum triglyceride-rich lipoprotein cholesterol (TRL-C) level [0.38 (0.32, 0.45) mmol/L vs. 0.46 (0.34, 0.54) mmol/L, p = 0.012] were significantly elevated in high SUA group. Additionally, serum ANGPTL4 in high SUA group was higher than in low SUA group [15.81 (11.88, 20.82) ng/ml vs. 22.13 (17.88, 32.09) ng/ml, p = 0.000]. Moreover, in all subjects, TRL-C levels were positively associated with SUA (r = 0.26, p = 0.023, n = 80) and ANGPTL4 levels (r = 0.24, p = 0.036, n = 80). Using stepwise multiple regression analysis to adjust for potential confounders, SUA was discovered to be an independent contributor to serum ANGPTL4 (p = 0.023). At the same time, serum ANGPTL4 was an independent contributor to the level of TRL-C (p = 0.000). However, the correlation between SUA and TRL-C disappeared after controlling for ANGPTL4 level.ConclusionSerum uric acid was positively correlated to TRL-C. ANGPTL4 may be an interplay between SUA and associated elevation of TRL-C.

MO150: Serum Angiopoietin-Like Protein 3 Level is Negatively Associated with Vascular Reactivity Index by Digital Thermal Monitoring in Chronic Haemodialysis Patients

Abstract BACKGROUND AND AIMS Angiopoietin-like protein 3 (ANGPTL3) plays important roles in lipid and lipoprotein trafficking and metabolism and has demonstrated a positive correlation with cardiovascular risk assessment parameters of carotid and femoral artery intima-media thickness. We evaluated the association between serum ANGPTL3 levels and endothelial function in chronic haemodialysis (HD) patients. METHOD Blood samples were obtained from 116 chronic HD patients. We measured the endothelial function—represented by the vascular reactivity index (VRI)—via non-invasive digital thermal monitoring, and serum ANGPTL3 concentrations by using commercial enzyme-linked immunosorbent assay. RESULTS A total of 17 (14.7%), 50 (43.1%) and 49 (42.2%) patients had poor (VRI &amp;lt; 1.0), intermediate (1.0 ≤ VRI &amp;lt; 2.0) and good (VRI ≥ 2.0) vascular reactivity. As the VRI decreased, the serum alkaline phosphatase (ALP, P = .025) and ANGPTL3 (P &amp;lt; .001) levels significantly increased. Serum log-transformed ALP (log-ALP, r = –0.187, P = .045) and log-ANGPTL3 (r = –0.319, P &amp;lt; .001) were negatively associated with VRI values by univariate linear regression analysis. After applying multivariate stepwise linear regression analysis adjustment, the significantly negative association of log-ANGPTL3 (standardized β = –0.319, adjusted R2 change = 0.094; P &amp;lt; .001) with VRI values in chronic HD patients remained. CONCLUSION Our study results indicated that ANGPTL3 concentration was negatively associated with VRI values and modulated endothelial function in chronic HD patients.

The Role of Serum Angiopoietin-Like Protein 4 (ANGPTL-4) and its Gene in Iraq Patients with Type2 Diabetes Mellitus: Case-Control Study

Background Type 2 Diabetes Mellitus is produced by cell failure of pancreatic cells and insulin resistance and is a disorder in which the amount of sugar in the blood is elevated. Angiopoietin-like protein 4 (ANGPTL4) functions as an inhibitor of lipoprotein lipase, a critical enzyme in lipid metabolism. The aim of this study was to explore if the ANGPTL4 gene's E40K variant and ANGPTL4 serum levels are related to the Body mass index, fasting glucose levels, lipid levels, and glycated hemoglobin.Method75 people were enrolled in this case-control study, 25 of whom had type 2 diabetes mellitus while the other 50 were healthy control subjects. Fasting blood glucose, Lipid profile, Glycated hemoglobin were estimated by Cobas 111 analyzer, BMI (weight, height) was calculated, angiopoietin-like protein 4by anenzyme-linked immune sorbent test kit and TaqMan genotyping-based real-time PCR was used to ascertain ANGPTL4 genotypes. The variant was linked to the risk of Type 2 Diabetes Mellitus and parameters used to quantify the variant were identified. Result Patients in the 30-50 age range with type 2 diabetes and those in the same age group who serve as controls. The control group had a lower level of angiopoietin-like protein 4 (ANGPTL4) than the diabetes group. Patients with T2DM had a substantially (p&lt; 0.0001) greater fasting serum Angiopoietin-like protein 4 level than the control group (135.1±6.70) ng/ml and (62.35±6.4) ng/ml, respectively. The diabetes group has significantly higher fasting serum glucose, lipid profile, and glycated hemoglobin compared with non-diabetics. Serum Angiopoietin-like protein 4 was correlated positively with body mass index. (CC,CT,TT) genotypes of the rs2010871 polymorphism There was a significant difference in frequency of the control group (p =0.0477); however, there was no significant difference in its level of (diabetics, newly diagnosed type 2 diabetic before treatment)p-value (0.7066, 0.5555) respectively Conclusion Serum Angiopoietin-like protein 4 levels are negatively correlated to cholesterol, positively correlated to triglyceride, negatively correlated to HDL, positively correlated to HbA1c, negatively correlated to LDL, negatively correlated to VLDL, negatively correlated to FBS, negatively correlated to BMI. The C&gt;T allele at the ANGPTL4 gene's rs2010871polymorphic locus was linked to a decreased prevalence of Type 2 diabetes.

Serum Angiopoietin-Like Protein 2 and NT-Pro BNP Levels and Their Associated Factors in Patients with Chronic Heart Failure Participating in a Phase III Cardiac Rehabilitation Program.

Angiopoietin-like protein 2 (ANGPTL2) promotes chronic inflammation and plays a key role in the pathogenesis of heart failure. Cardiac rehabilitation (CR) is an integral component of heart failure management and has been shown to have anti-inflammatory effects. However, ANGPTL2 concentration in chronic heart failure patients undergoing CR has not been evaluated. This study aimed to investigate serum ANGPTL2 levels and their associated factors and compare the results with those of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with chronic heart failure undergoing phase III CR.A total of 56 patients were enrolled. Clinical characteristics including body composition, grip strength, exercise tolerance, duration of CR, blood counts and biochemistry, and echocardiographic parameters were evaluated for their association with serum ANGPTL2 and NT-proBNP levels.The median (first and third quartiles) value of ANGPTL2 was 4.05 (2.70-5.57) ng/mL. Clinical parameters that correlated with serum ANGPTL2 levels were body weight, body mass index, body fat mass, body fat percentage, anaerobic threshold (AT), C-reactive protein, and total protein (TP), which were mostly distinct from those that correlated with serum NT-proBNP levels. A multivariate analysis revealed that AT and TP were independent factors related to ANGPTL2 levels, whereas age, left ventricular ejection fraction, and left atrial dimension were independently related to NT-proBNP levels.These observations suggest that CR increases the exercise tolerance and exhibits anti-inflammatory effects simultaneously, and this situation is reflected by decreased serum ANGPLT2 and TP levels. ANGPTL2 may be a useful marker of inflammation and impaired exercise tolerance in patients with chronic heart failure.

Serum Angiopoietin-like Protein 3 Level Is Associated with Peripheral Arterial Stiffness in Patients with Coronary Artery Disease.

Background and Objectives: Angiopoietin-like protein 3 (ANGPTL3) is a secretory protein regulating lipid metabolism. This study evaluated the relationship between serum ANGPTL3 level and peripheral arterial stiffness (PAS) in patients with coronary artery disease (CAD). Materials and Methods: Fasting blood samples were collected from 95 CAD patients. PAS was defined as left or right brachial-ankle pulse wave velocity (baPWV) > 18.0 m/s by an oscillometric method. Serum ANGPTL3 levels were assessed using a commercial enzyme-linked immunosorbent assay kit. Results: Seventeen CAD patients (17.9%) had PAS. Patients with PAS had a significantly higher percentage of diabetes (p = 0.002), older age (p = 0.030), higher systolic blood pressure (p = 0.016), higher fasting glucose (p = 0.008), serum C-reactive protein (p = 0.002), and ANGPTL3 level (p = 0.001) than those without PAS. After multivariable logistic regression analysis, serum ANGPTL3 level (Odds ratio (OR): 1.004, 95% confidence interval (CI): 1.000–1.007, p = 0.041) is still independently associated with PAS in CAD patients. The receiver operating characteristic curve for PAS prediction revealed that the area under the curve for ANGPTL3 level was 0.757 (95% CI: 0.645–0.870, p < 0.001). Conclusions: Serum fasting ANGPTL3 level is positively associated with PAS in CAD patients. Further studies are required for clarification.

Positive correlation of serum angiopoietin-like protein 3 levels with metabolic syndrome in patients with coronary artery disease.

Objectives:Angiopoietin-like protein 3 (ANGPTL3) regulates triglyceride metabolism by reversibly inhibiting the lipoprotein lipase activity. Metabolic syndrome (MetS) is an independent risk factor for further cardiovascular disease. This study evaluated the relationship between the fasting serum ANGPTL3 levels and MetS in patients with coronary artery disease (CAD).Materials and Methods:Fasting blood samples were obtained from 90 patients with CAD. Serum ANGPTL3 levels were measured using a commercial enzyme-linked immunosorbent assay kit. MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation.Results:Fifty-three patients (58.9%) had MetS. The hypertension (P = 0.001), diabetes (P < 0.001), body weight (P = 0.027), body mass index (P = 0.001), waist circumference (P < 0.001), systolic blood pressure (P = 0.001), fasting glucose (P < 0.001), triglycerides (P < 0.001), blood urea nitrogen (P = 0.044), C-reactive protein (P = 0.010), insulin (P = 0.040), homeostasis model assessment of insulin resistance (P = 0.002), and ANGPTL3 level (P = 0.001) of CAD patients who had MetS were higher, and the high-density lipoprotein cholesterol (P = 0.001) and estimated glomerular filtration rate (P = 0.016) were lower. A binary logistic regression analysis of the significant variables also revealed that the ANGPTL3 level (odds ratio: 1.023, 95% confidence interval: 1.008–1.038, P = 0.002) was an independent predictor of MetS in patients with CAD.Conclusion:The results of our study indicated that the fasting ANGPTL3 level was positively associated with MetS among patients with CAD.

Evaluation of serum Angiopoietin-like protein 2 (ANGPTL-2), Angiopoietin-like protein 8 (ANGPTL-8), and high-sensitivity C-reactive protein (hs-CRP) levels in patients with gestational diabetes mellitus and normoglycemic pregnant women

Objective In the present study, we aimed to investigate the role of the fasting serum levels of Anjiopoetın 2 - like protein (ANGPTL2), Anjiopoetın 8-like protein (ANGPTL8), and high-sensitivity C-reactive protein (hs-CRP) in the etiopathogenesis of gestational diabetes mellitus (GDM), and analyze the relationships between insulin resistance parameters. Material and method The 90 individuals admitted to İzmir Katip Celebi University Hospital Internal Medicine, Endocrinology and Obstetrics, and gynecology outpatient clinic were included in the study of similar ages and similar demographic characteristics. Forty-five women with diet-controlled GDM and 45 women with normoglycemic pregnancy were enrolled. ANGPTL-2, ANGPTL-8, hs-CRP, creatinine, ALT, GGT, lipid profile, HBA1c(%), and serum insülin, c-peptide levels were studied in the fasting serum samples of research groups. All individuals had 75-g OGTT testing. GDM screening was performed at 24–28 weeks’ gestation. Exclusion criteria were as follows: Age <18 years or >40 years, pregestational diabetes (type 1 or 2), drug or alcohol abuse, thyroid dysfunction, Hepatitis B, and other infectious diseases (Herpes virus, Streptococcus B carriers, Chlamydia and Candida), Thalassemia carriers or other significant medical conditions, the use of any medication that interferes with lipid or glucose metabolism that would affect glucose regulation. Result Forty-five women with GDM and for the control group, 45 women with normoglycemic pregnant women were identified. The mean gestational age was 30.7 (18–38) for GDM and 29.6 (24–39) for the control group. Serum ANGPTL-8 (GDM =19.5 ± 93 Control = 0.73 ± 3.78 p = <.001). There was a statistically significant difference between the case and control groups for serum ANGPTL-8 levels. Serum ANGPTL-2 (GDM =19.9 ± 23.1 Control = 26.0 ± 23.4 p = .105) and serum hs-CRP(GDM =106 ± 65.1 Control =98.2 ± 87.3 p = .768). There was no statistically significant difference between the case and control groups for serum ANGPTL-2 and hsCRP levels. Serum ANGPTL8 levels were positively correlated with FPG (r = 0.391, p = <.001), FPI (r = 0.212, p = .045), 1-h PPG (r = 0.514, p = <.001), 2-h PPG (r = 0.502, p = <.001), HOMA-IR) score (r = 0.310, p = .003), TG (r = 0.245, p = .020); they were not except for BMI, hs-CRP levels and ANGPTL2 levels. Conclusions ANGPTL8 levels were significantly higher in GDM than in healthy control group. ANGPTL2 levels and hs-CRP levels were similar to the healthy control group. Elevated serum ANGPTL8 levels were correlated significantly with insulin resistance parameters, the main component of GDM pathophysiology. Our data showed that ANGPTL8 could be a new biomarker for diagnosing GDM.

Dietary modification reduces serum angiopoietin-like protein 2 levels and arterial stiffness in overweight and obese men.

Weight loss can reduce obesity-induced arterial stiffening that is attributed to decreased inflammation. Angiopoietin-like protein 2 (ANGPTL2) is a pro-inflammatory adipokine that is upregulated in obesity and is important in the progression of atherosclerosis and cardiovascular disease. The purpose of this study is to investigate the effects of dietary modification on circulating ANGPTL2 levels and arterial stiffness in overweight and obese men. Twenty-two overweight and obese men (with mean age of 56 ± 2 years and body mass index of 28.6 ± 2.6 kg/m2) completed a 12-week dietary modification program. We measured the arterial compliance and β-stiffness index (as the indices of arterial stiffness) and serum ANGPTL2 levels before and after the program. After the 12-week dietary modification, body mass and daily energy intake were significantly reduced. Arterial compliance was significantly increased and β-stiffness index was significantly decreased after the 12-week dietary modification program. Serum ANGPTL2 levels were significantly decreased. Also, the changes in arterial compliance were negatively correlated with the changes in serum ANGPTL2 levels, whereas the changes in β-stiffness index were positively correlated with the changes in serum ANGPTL2 levels. These results suggest that the decrease in circulating ANGPTL2 levels can be attributed to the dietary modification-induced reduction of arterial stiffness in overweight and obese men.

Association of serum angiopoietin-like protein 2 with elevated risk of cardiovascular diseases in subjects with type 2 diabetes

AimsAlthough previous data have suggested ANGPTL2 and ANGPTL8 (betatrophin) to be related to atherosclerosis in humans, little is known whether this applies in patients with type 2 diabetes (T2D). In this work, we investigate association of serum ANGPTL2 and betatrophin with the risk of cardiovascular diseases (CVD) in T2D patients. MethodsWe measured serum levels of ANGPTL2 and betatrophin in 150 T2D patients with and without CVD and in 100 control subjects. ResultsSerum ANGPTL2 was significantly higher in T2D patients than in controls (p < 0.0001), and in T2D + CVD patients than T2D only patients (p = 0.0002). Serum betatrophin was lower in T2D patients than in controls but with no statistical significance (p = 0.07). Elevated serum ANGPTL2 associated with 2.83-fold increased risk of T2D and with 1.18-fold elevated risk of CVD among T2D patients with positive correlations with markers of hyperglycemia, insulin resistance and atherogenic lipid profile. ROC curve indicated ANGPTL2 as risk biomarker for T2D and CVD with sensitivity of 92.2% and 86%; and specificity of 86.7% and 58%; respectively. ConclusionWe indicate for the first time serum ANGPTL2 as an independent risk biomarker for CVD in T2D patients. Future studies are needed to reveal its role in disease pathogenesis.

Triglyceride-mediated influence of serum angiopoietin-like protein 8 on subclinical atherosclerosis in type 2 diabetic patients: results from the GDMD study in China

BackgroundHypertriglyceridemia, insulin resistance and hyperglycemia are risk factors for atherosclerosis in type 2 diabetes. Angiopoietin-like protein 8 (ANGPTL8) is a newly identified liver-derived hormone related to these risk factors. Hence, we aimed to explore the correlations between serum levels of ANGPTL8 and subclinical atherosclerosis in type 2 diabetes.MethodsWe measured serum ANGPTL8, blood lipids, blood glucose, common carotid artery Intima-Media Thickness (c-IMT) and calculated homeostasis model assessment of insulin resistance in (1) control subjects (n = 100), (2) type 2 diabetic patients without subclinical atherosclerosis (n = 100), and (3) type 2 diabetic patients with subclinical atherosclerosis (n = 100).ResultsSerum levels of ANGPTL8 and triglyceride (TG) were significantly increased in type 2 diabetic patients with subclinical atherosclerosis as compared with type 2 diabetic patients without subclinical atherosclerosis and control subjects (P < 0.001). ANGPTL8 was positively associated with age, TG, diabetes duration, and c-IMT in type 2 diabetes. Logistic regression analysis revealed that ANGPTL8 had higher odds of having subclinical atherosclerosis [odds ratio (OR) 2.90, 95% confidence interval (CI) 1.48–5.70, P = 0.002] in type 2 diabetes. Mediation analysis indicated that TG acted as a partial mediator in the relationship between ANGPTL8 and c-IMT.ConclusionsTG partially mediates the positive relationship between ANGPTL8 and c-IMT. Our data provide the first evidence for a strong link between ANGPTL8 and subclinical atherosclerosis, suggesting ANGPTL8 to be a new biomarker for subclinical atherosclerosis in type 2 diabetes.

GLP-1 receptor agonists stimulate ANGPTL8 production through the PI3K/Akt pathway in a GLP-1 receptor-dependent manner

The level of serum angiopoietin-like protein 8 (ANGPTL8), a novel hepatokine, is associated with obesity and type 2 diabetes mellitus (T2DM). The aims of this study were to investigate whether serum ANGPTL8 level in patients with T2DM was affected by treatment with exenatide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, and to determine whether and how GLP-1R agonists regulated ANGPTL8 production in hepatocytes. A multiple-center trial was conducted in China. Among 240 patients with T2DM enrolled in this trial, 195 patients adhered to a 16-week exenatide treatment and follow-up. Human liver cell line HepG2 cells were incubated for 24 h with either exendin-4 (a native form of exenatide) or liraglutide in the presence or absence of GLP-1R antagonist exendin (9–39) and PI3K inhibitor LY294002. Change of serum ANGPTL8 level in patients with T2DM and regulation of ANGPTL8 production by the GLP-1R agonists in HepG2 cells were evaluated. Results showed that compared with baseline, exenatide treatment significantly increased serum ANGPTL8 level, and lowered body weight, fasting blood glucose (FBG) and glycated hemoglobin A1c (HbA1c) in patients with T2DM (all P < 0.05). The exenatide treatment-mediated upregulation of serum ANGPTL8 level was not associated with the levels of its lowering effects on body weight, FBG and HbA1c stratified by the median. Moreover, exendin-4 or liraglutide dose-dependently upregulated the level of ANGPTL8 expression and secretion in HepG2 cells, which was eliminated by adding exendin (9–39) and LY294002. In conclusion, GLP-1R agonists enhance ANGPTL8 production in vivo and in vitro, which is mediated via the PI3K/Akt pathway in a GLP-1R-dependent manner.