Predictive value of angiopoietin-like protein 8 in metabolic dysfunction-associated fatty liver disease and its progression:A case-control study

BACKGROUND The prevalence of metabolic dysfunction-associated fatty liver disease(MAFLD)is rapidly increasing,currently affecting approximately 25%of the global population.Liver fibrosis represents a crucial stage in the development of MAFLD,with advanced liver fibrosis elevating the risks of cirrhosis and hepatocellular carcinoma.Simple serum markers are less effective in diagnosing liver fibrosis compared to more complex markers.However,imaging techniques like transient elastography face limitations in clinical application due to equipment and technical constraints.Consequently,it is imperative to identify a straightforward yet effective method for assessing MAFLD-associated liver fibrosis.AIM To investigate the predictive value of angiopoietin-like protein 8(ANGPTL8)in MAFLD and its progression.METHODS We analyzed 160 patients who underwent abdominal ultrasonography in the Endocrinology Department,Xiaogan Central Hospital affiliated to Wuhan University of Science and Technology,during September 2021-July 2022.Using abdominal ultrasonography and MAFLD diagnostic criteria,among the 160 patients,80 patients(50%)were diagnosed with MAFLD.The MAFLD group was divided into the liver fibrosis group(n=23)and non-liver fibrosis group(n=57)by using a cut-off fibrosis-4 index≥1.45.Logistical regression was used to analyze the risk of MAFLD and the risk factors for its progression.Receiver operating characteristic curves were used to evaluate the predictive value of serum ANGPTL8 in MAFLD and its progression.RESULTS Compared with non-MAFLD patients,MAFLD patients had higher serum ANGPTL8 and triglyceride-glucose(TyG)index(both P<0.05).Serum ANGPTL8(r=0.576,P<0.001)and TyG index(r=0.473,P<0.001)were positively correlated with MAFLD.Serum ANGPTL8 was a risk factor for MAFLD[odds ratio(OR):1.123,95%confidence interval(CI):1.066-1.184,P<0.001).Serum ANGPTL8 and ANGPTL8+TyG index predicted MAFLD[area under the curve(AUC):0.832 and 0.886,respectively;both P<0.05].Compared with MAFLD patients without fibrosis,those with fibrosis had higher serum ANGPTL8 and TyG index(both P<0.05),and both parameters were positively correlated with MAFLD-associated fibrosis.Elevated serum ANGPTL8(OR:1.093,95%CI:1.044-1.144,P<0.001)and TyG index(OR:2.383,95%CI:1.199-4.736,P<0.013)were risk factors for MAFLD-associated fibrosis.Serum ANGPTL8 and ANGPTL8+TyG index predicted MAFLD-associated fibrosis(AUC:0.812 and 0.835,respectively;both P<0.05).CONCLUSION The serum levels of ANGPTL8 are elevated and positively correlated with MAFLD.They can serve as predictors for the risk of MAFLD and liver fibrosis,with the ANGPTL8+TyG index potentially exhibiting even higher predictive value.

Clinical and experimental study on angiopoietin-like protein 8 associated with proliferative diabetic retinopathy

AIM：To confirm the role of angiopoietin-like protein 8（Angptl 8） in proliferative diabetic retinopathy（PDR）.METHODS：The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy（NDR） patients（idiopathic macular hole patients） were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay（ELISA）.Experimental diabetes mice model was induced with streptozotocin.The expression of glycosylated hemoglobin and Angptl 8 in sera was detected.Recombinant Angptl 8 was re-infused into wild type（WT） diabetic mice and spatial frequency threshold and contrast sensitivity were measured.In vitro retinal pigment epithelium（RPE） were stimulated by recombinant Angptl 8 for 24 h.MMT assay were used to detect cell proliferation.At the same time,q RT-PCR and Western blot was used to measure the expression of proliferation-related factors in PRE cells.RESULTS：The expression of Angptl 8 was markedly increased in the sera and aqueous humor of PDR patients（F=99.02,P〈0.0001 in sera;t=10.42,P〈0.0001 in aqueous）.After successfully establishing the diabetic mice model,we found that glycosylated hemoglobin and Angptl 8 expression levels were increased.Re-infusion of recombinant Angptl 8 into WT diabetic mice could further decrease spatial frequency threshold and contrast sensitivity（P〈0.01）.In vitro,RPE cells stimulated by recombinant Angptl 8could increase the relative absorbance of MMT assay（1.486±0.042 vs 1.000±0.104,P〈0.05） and proliferating cell nuclear antigen（PCNA） expression（0.55±0.01 vs 0.29±0.03,P〈0.05）.The proliferative effect of Angptl 8 is mainly mediated by increasing the expression of proliferation-activating factors cyclin A1（4.973±0.205 vs 2.720±0.197,P〈0.05）,cyclin F（5.690±0.219 vs 4.297±0.292,P〈0.05） and E2 F2（2.297±0.102 vs 1.750±0.146,P〈0.05）,and reducing the expression of proliferation-inhibiting factors cdkn1（2.370±0.074 vs 3.317±0.135,P〈0.05） and cdkn2（4.793±0.065 vs 5.387±0.149,P〈0.05）.CONCLUSION：The expression of Angptl 8 is increased in PDR,and the increased Angptl 8 can promote proliferation and increase proliferation-related factors.

Recombinant angiopoietin-like protein 4 attenuates intestinal barrier structure and function injury after ischemia/reperfusion

BACKGROUND Intestinal barrier breakdown,a frequent complication of intestinal ischemiareperfusion(I/R)including dysfunction and the structure changes of the intestine,is characterized by a loss of tight junction and enhanced permeability of the intestinal barrier and increased mortality.To develop effective and novel therapeutics is important for the improvement of outcome of patients with intestinal barrier deterioration.Recombinant human angiopoietin-like protein 4(rhANGPTL4)is reported to protect the blood-brain barrier when administered exogenously,and endogenous ANGPTL4 deficiency deteriorates radiationinduced intestinal injury.AIM To identify whether rhANGPTL4 may protect intestinal barrier breakdown induced by I/R.METHODS Intestinal I/R injury was elicited through clamping the superior mesenteric artery for 60 min followed by 240 min reperfusion.Intestinal epithelial(Caco-2)cells and human umbilical vein endothelial cells were challenged by hypoxia/reoxygenation to mimic I/R in vitro.RESULTS Indicators including fluorescein isothiocyanate-conjugated dextran(4 kilodaltons;FD-4)clearance,ratio of phosphorylated myosin light chain/total myosin light chain,myosin light chain kinase and loss of zonula occludens-1,claudin-2 and VE-cadherin were significantly increased after intestinal I/R or cell hypoxia/reoxygenation.rhANGPTL4 treatment significantly reversed these indicators,which were associated with inhibiting the inflammatory and oxidative cascade,excessive activation of cellular autophagy and apoptosis and improvement of survival rate.Similar results were observed in vitro when cells were challenged by hypoxia/reoxygenation,whereas rhANGPTL4 reversed the indicators close to normal level in Caco-2 cells and human umbilical vein endothelial cells significantly.CONCLUSION rhANGPTL4 can function as a protective agent against intestinal injury induced by intestinal I/R and improve survival via maintenance of intestinal barrier structure and functions.

Angiopoietin-like protein 3 (ANGPTL3) deficiency and familial combined hypolipidemia

Three members of the angiopoietin-like(ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8-are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the intravascular lipolysis of triglycerides present in some lipoprotein classes. This review focuses on the role of ANGPTL3 as emerged from the study of genetic variants of Angptl3 gene in mice and humans. Both loss of function genetic variants and inactivation of Angptl3 gene in mice are associated with a marked reduction of plasma levels of triglyceride and cholesterol and an increased activity of lipoprotein lipase and endothelial lipase. In humans with ANGPTL3 deficiency, caused by homozygous loss of function(LOF) variants of Angptl3 gene, the levels of all plasma lipoproteins are greatly reduced. This plasma lipid disorder referred to as familial combined hypolipidemia(FHBL2) does not appear to be associated with distinct pathological manifestations. Heterozygous carriers of LOF variants have reduced plasma levels of total cholesterol and triglycerides and are at lower risk of developing atherosclerotic cardiovascular disease, as compared to non-carriers. These observations have paved the way to the development of strategies to reduce the plasma level of atherogenic lipoproteins in man by the inactivation of ANGPTL3, using either a specific monoclonal antibody or anti-sense oligonucleotides.

Aqueous angiopoietin-like levels correlate with optical coherence tomography angiography metrics in diabetic macular edema

AIM:To quantitatively detect aqueous levels of angiopoietin-like(ANGPTL)3,ANGPTL4,and ANGPTL6 and investigate their correlation with optical coherence tomography angiography(OCTA)findings in patients with diabetic macular edema(DME).METHODS:This cross-sectional study included 23 patients(27 eyes)with type 2 diabetes and 16 control subjects(20 eyes).All patients underwent OCTA imaging and ultra-wide field fundus photography.Diabetic patients were categorized into two groups according to the presence or absence of diabetic retinopathy(DME group,14 patients,16 eyes);and non-diabetic retinopathy(NDR)group,9 patients,11 eyes,respectively.Aqueous levels of ANGPTL3,ANGPTL4,and ANGPTL6 were assessed using suspension array technology,and foveal-centered 3×3 mm2 OCTA scans were automatically graded to determine the central,inner,and full vessel density(CVD,IVD,FVD);central,inner,and full perfusion density(CPD,IPD,FPD),foveal avascular zone(FAZ)area,FAZ perimeter,and FAZ circularity index(FAZ-CI)on superficial capillary plexuses.Additionally,central subfield thickness(CST),cube volume(CV),and cube average thickness(CAT)were measured in a model of macular cube 512×128.RESULTS:Aqueous ANGPTL3 levels were not significantly different among the three groups(P>0.05).ANGPTL4 levels were significantly higher in the DME group than the control and NDR groups(P<0.0001 and P<0.001),while ANGPTL6 levels were significantly higher in the DME group than the control group(P<0.05).In the whole cohort,the aqueous ANGPTL3 levels correlated negatively with the IVD,FVD,IPD,and FPD,and positively with the CV and CAT.The aqueous ANGPTL4 levels correlated negatively with the CVD,IVD,FVD,CPD,IPD,and FPD,and positively with the FAZ perimeter,CST,CV,and CAT.The aqueous ANGPTL6 levels correlated negatively with the IVD,FVD,IPD,FPD,FAZCI and positively with CST,CV,CAT.CONCLUSION:ANGPTL4 and ANGPTL6 may be associated with vascular leakage in DME and may represent good targets for DME therapy.In addition,OCTA metrics may be useful for evaluating macular ischemia in DME.

Angiopoietin-Like Protein 3 Expression is Down-Regulated in Experimentally Pregnant Toxemic Goats

Pregnancy toxemia is a metabolic disorder of lipid and glucose. Recent investigations have found that angiopoietin-like protein 3 （ANGPTL3） can contribute to disorder of carbohydrate and lipid metabolism. The present study was conducted to investigate the change of ANGPTL3 expression during pregnancy toxemia, We firstly cloned the full-length cDNA of ANGPTL3 in Liuyang Black goats, revealing that goat ANGPTL3 had the typical structure of the angiopoietin-like family, and its mRNA was exclusively expressed in liver. Pregnancy toxemia of pregnant goat does with twins during late gestation was induced by being fasted for 72 h, and then they were recovered after 5 d ofrefeeding. Hepatic ANGPTL3 gene expression was significantly down-regulated concomitantly with decreased serum glucose concentration, elevated serum β-hydroxybutyrate and free fatty acid levels in pregnant toxemic goats, and these changes were reversed after refeeding. These results suggest ANGPTL3 may play a certain role in the development of pregnancy toxemia in goats.

Effect of human angiopoietin-like protein 4 overexpression on the growth of esophageal carcinoma EC9706 cells

Objective： The aim of the study was to construct the eukaryotic expression vector of human angiopoietin-like protein 4 （ANGPTL4） and observe the effect of ANGPTL4 overexpression on the growth of esophageal carcinoma EC9706 cells. Methods： Total RNA was extracted from normal hepatic tissue, and ANGPTL4 cDNA was amplified by RT-PCR. The PCR product was doubly digested by Xbal and Sail, and then recombined into eukaryotic expression vector. Then, plRES-GFP-ANGPTL4 was obtained by G418 selection, then plRES-GFP-ANGPTL4 and plRES-GFP were transfected into EC9706 cells with lipidosome-packaged method. Meanwhile, the transfected cells were selected by G418, and then stable transfected cell lines were obtained. ANGPTL4 mRNA levels, the celt cycles and growth curves of EC9706 cells in experiment group （transfected with plRES-GFP-ANGPTL4）, empty vector group （transfected with plRES-GFP） and blank control group （EC9706 cells without transfection） were detected with RT-PCR, flow cytometry and MTT methods, respectively. Results： Eukaryotic ANGPTL4 expression vector plRES-GFP-ANGPTL4 was successfully constructed. The ANGPTL4 mRNA level （0.21 ± 0.03） in experiment group was significantly higher than that of the empty vector group （0.04 ± 0.008） and the blank control group （0.05 ± 0.007）, with significant differences （P 〈 0.01）. The proportion of cells in S phase in experiment group was significantly different with those of the other two groups （P 〈 0.05）. The cell growth of EC9706 cells in experiment group was slower than those of the other two groups. From the third day, the differences began to be significant. Conclusion： ANGPTL4 overexpression in esophageal carcinoma EC9706 cells could inhibit the growth of EC9706 cells.

Host Factors Alter Effects of Angiopoietin-Like Protein 8 on Glucose Homeostasis in Diabetic Mice

Recovery of functional beta cell mass offers a biological cure for type 1 diabetes. However, beta cell mass is difficult to regain once lost since the proliferation rate of beta cells after youth is very low. Angiopoietin like-protein 8 (ANGPTL8), a peptide that has a role in the regulation of lipoprotein lipase activity, was reported to increase beta cell proliferation in mice in 2013. Subsequent studies of human ANGPTL8 for short term (3 to 8 days) in non-diabetic mice showed little or no increase in beta cell proliferation. Here, we examined the effect of ANGPTL8 on glucose homeostasis in models that have not been examined previously. We expressed mouse ANGPTL8 using adenovirus in 2 mouse models of diabetes (streptozotocin and Non-Obese Diabetic (NOD) mice) over 2 weeks. Also, we tested ANGPTL8 in NOD mice deficient in leukocyte 12-lipoxygenase (12LO), an enzyme that contributes to insulitis and loss of beta cell function in NOD, in an effort to determine whether 12LO deficiency alters the response to ANGPTL8. Adenovirus-mediated expression of ANGPTL8 lowered blood glucose levels in streptozotocin treated mice without an increase in beta cell proliferation or serum insulin concentration. While ANGPTL8 did not reverse hyperglycemia in overtly hyperglycemic NOD mice or alter glucose homeostasis of non-diabetic NOD mice, ANGPTL8 reduced blood glucose levels in 12LOKO NOD mice. However, the lower glucose levels in 12LOKO NOD were not associated with higher serum insulin levels or beta cell proliferation. In summary, while mouse ANGPTL8 does not increase beta cell proliferation in NOD mice or streptozotocin treated mice in agreement with studies in non-diabetic mice, it lowers blood glucose levels in multiple low-dose streptozotocin induced diabetes and 12LO deficiency indicating that host factors influence the impact of ANGPTL8 on glucose homeostasis.

Association between Maternal Serum Concentrations of Angiopoietin-like Protein 2 in Early Pregnancy and Subsequent Risk of Gestational Diabetes Mellitus

Background：A recent study reported a positive association between elevated serum levels of angiopoietin-like protein 2 （ANGPTL2） and the development of type 2 diabetes in a general population.However,the relationship of serum ANGPTL2 levels with the risk of developing gestational diabetes mellitus （GDM） has not been reported to date.The aim of this study was to investigate the change of maternal serum ANGPTL2 concentrations in the first trimester of pregnancy and to determine whether ANGPTL2 is a biomarker for subsequent GDM development.Methods：We conducted a prospective,nested case-control study in a pregnancy cohort.First-trimester ANGPTL2 levels were measured using a high-resolution assay in 89 women who subsequently developed GDM and in a random sample of 177 women who remained euglycemic throughout the pregnancy.Median ANGPTL2 levels were compared using Mann-Whitney U-test.Logistic regression was used to compute unadjusted and multivariable-adjusted odds ratios for developing GDM among ANGPTL2 quartiles.Results：The serum levels of ANGPTL2 was higher in women with GDM than that in women without GDM （3.06 [2.59,3.65] ng/ml vs.2.46 [2.05,2.96] ng/ml,P =0.003）.Fasting blood glucose was higher in women with GDM than that in women without GDM （5.0 ± 0.9 mmol/L vs.4.4 ± 0.6 mmol/L,P 〈 0.001）.Glucose challenge test showed that the blood glucose was higher in women with GDM than that in women without GDM （9.1 ± 3.5 mmol/L vs.6.2 ± 1.2 mmol/L,P 〈 0.001）.A multivariate model adjusted for baseline characteristics,medical complications,and gestational characteristics revealed that the risk of developing GDM among women in Q4 compared with Q1 was 2.90-fold more likely to develop GDM later in pregnancy.Conclusions：At 1 1-13 weeks in pregnancies that develop GDM,the serum concentration of ANGPTL2 is increased,and it can be combined with maternal factors to provide effective early screening for GDM.

Dynamic roles of angiopoietin-like proteins 1, 2, 3, 4, 6 and 7 in the survival and enhancement of ex vivo expansion of bone-marrow hematopoietic stem cells

Recent advances in hematopoietic stem cells(HSCs)expansion by growth factors including angiopoietin-like proteins(Angptls)have opened up the possibility to use HSCs in regenerative medicine.However,the unavailability of true in vitro HSCs expansion by these growth factors has limited the understanding of the cellular and molecular mechanism of HSCs expansion.Here,we report the functional role of mouse Angptls 1,2,3,4,6 and 7 and growth factors SCF,TPO,IGF-2 and FGF-1 on purified mouse bone-marrow(BM)Lineage-Sca-1+(Lin-Sca-1+)HSCs.The recombinant retroviral transduced-CHO-S cells that secrete Angptls in serum-free medium were used alone or in combination with growth factors(SCF,TPO,IGF-2 and FGF-1).None of the Angptls stimu-lated HSC proliferation,enhanced or inhibited HSCs colony formation,but they did support the survival of HSCs.By contrast,any of the six Angptls together with saturating levels of growth factors dramatically stimulated a 3-to 4.5-fold net expansion of HSCs compared to stimulation with a combination of those growth factors alone.These findings lead to an understanding of the basic function of Angptls on signaling pathways for the survival as well as expansion of HSCs in the bone marrow niche.

Lipopolysaccharide-induced podocyte injury is regulated by calcineurin/NFAT and TLR4/MyD88/NF-κB signaling pathways through angiopoietin-like protein 4

Podocyte injury is an important cause of proteinuria.Angiopoietin-like protein 4(Angptl4)is a secreted glycoprotein and has a role in proteinuria.However,the exact role of Angptl4 in podocyte injury and its upstream regulators has not been clarified.In this study,we used lipopolysaccharide(LPS)-induced mice and cultured podocytes as podocyte injury models.Our results indicated that LPS increased the expression of podocyte Angptl4 in vivo and in vitro.Furthermore,we showed that Angptl4 overexpression deteriorated LPS-induced podocyte injury by inducing podocyte cytoskeleton rearrangement,reducing the expression of synaptopodin while Angptl4 knockdown alleviated LPS-induced podocyte injury.In addition,we found that inhibitors and siRNA targeting TLR4/MyD88/NF-κB signaling inhibited the upregulation of Angptl4 in LPS-induced podocytes.Moreover,inhibitors and siRNA targeting calcineurin/NFAT signaling also relieved LPS-induced Angptl4 expression and podocyte injury in vivo and in vitro.Taken together,our study has elucidated that both of the TLR4/MyD88/NF-κB and calcineurin/NFAT signaling mediate the upregulation of Angptl4 in LPS-induced podocytes,which has important implications for further understanding the molecular mechanism of LPS-induced podocyte injury.

多发性子宫肌瘤患者血清ANGPTL2、VASH1的表达及临床意义

目的 分析血清中血管生成素样蛋白2(ANGPTL2)和血管生成抑制蛋白1(VASH1)的表达水平,探讨其在多发性子宫肌瘤中的临床意义。方法 选取2018年1月至2022年1月于东南大学医学院附属南京同仁医院就诊的312例多发性子宫肌瘤患者为研究对象(观察组),同时期来本院体检的312名健康女性作为对照(对照组);酶联免疫吸附试验(ELISA)检测血清中ANGPTL2和VASH1水平;Pearson相关分析血清中ANGPTL2和VASH1水平的相关性;受试者工作特征(ROC)曲线分析血清中ANGPTL2和VASH1水平对多发性子宫肌瘤的诊断价值;Logistic回归分析多发性子宫肌瘤发生的影响因素。结果 观察组血清中ANGPTL2和VASH1水平显著高于对照组,差异有统计学意义(t=12.870、9.935,P<0.05);血清中ANGPTL2和VASH1水平与阴道不规则出血、肌瘤数量、最大肌瘤直径以及平均肌瘤体积有关,差异有统计学意义(P<0.05),而与年龄、月经情况、绝经情况、妊娠史、流产史、ER、PR以及肿瘤部位无关,差异无统计学意义(P>0.05);Pearson相关分析结果显示,多发性子宫肌瘤患者血清中ANGPTL2和VASH1水平呈正相关(r=5.440,P<0.05);ROC曲线分析结果显示,血清中ANGPTL2和VASH1水平联合诊断多发性子宫肌瘤的曲线下面积(AUC),效果较ANGPTL2和VASH1单一指标更好(P<0.05);Logistic回归分析结果显示,ANGPTL2、VASH1是多发性子宫肌瘤发生的影响因素(P<0.05)。结论 多发性子宫肌瘤患者血清中ANGPTL2和VASH1水平显著升高,两者联合可辅助诊断多发性子宫肌瘤。

血管生成素样蛋白4通过调节成纤维细胞和内皮细胞功能影响糖尿病足进程

背景:研究表明,血管因素对糖尿病足的发生具有重要影响。目的:探讨血管生成素样蛋白4在糖尿病足形成中的重要作用。方法:①对糖尿病足患者的基因表达谱数据进行生物信息学分析,找到关键基因。收集糖尿病足患者以及无糖尿病健康人的皮肤标本进行苏木精-伊红染色、免疫组化染色以及qRT-PCR实验,检测血管生成素样蛋白4表达情况。②培养人永生化皮肤成纤维细胞系和原代人脐静脉内皮细胞,将2种细胞分别分为对照组和外源性补充血管生成素样蛋白4组,通过划痕实验以及CCK-8实验分别检测成纤维细胞的迁移能力和增殖能力,通过Ki67实验检测内皮细胞的增殖能力。结果与结论:①生信分析发现,血管生成素样蛋白4基因的下调可能是导致糖尿病足形成的关键基因。②苏木精-伊红染色结果显示,与正常皮肤相比,血管生成素样蛋白在糖尿病足皮肤内弱表达,且其mRNA水平相对表达量降低(P<0.01)。③划痕实验结果显示,与对照组相比,血管生成素样蛋白4组成纤维细胞迁移能力明显增强;CCK-8细胞增殖实验显示,血管生成素样蛋白4组成纤维细胞的吸光度值在24,48 h均高于对照组(P<0.01,P<0.001);提示血管生成素样蛋白4可增强高糖处理的成纤维细胞迁移及增殖能力。④Ki67实验结果显示,与对照组相比,血管生成素样蛋白4组内皮细胞Ki67阳性细胞数目明显多于对照组;CCK-8细胞增殖实验显示,血管生成素样蛋白4组内皮细胞的吸光度值在24,48 h均高于对照组(P<0.05,P<0.001)。(5)以上结果均提示血管生成素样蛋白4可增强高糖处理内皮细胞的增殖能力。

血清miR-124、CD146及Angptl2水平与急性脑梗死患者颈动脉粥样硬化斑块稳定性的关系研究

目的探讨血清微小RNA-124(miR-124)、CD146、血管生成素样蛋白2(Angptl2)与急性脑梗死(ACI)患者颈动脉粥样硬化(CAS)斑块稳定性的关系,为ACI患者的早期防治提供参考依据。方法选择2020年1月至2023年2月在邯郸市中心医院就诊的ACI患者191例作为ACI组,另选取同期在该院体检的健康志愿者61例作为对照组。根据颈动脉彩色多普勒超声结果将ACI患者分为不稳定斑块组(56例)、稳定斑块组(71例)、无斑块组(64例)。采用实时荧光定量聚合酶链式反应(RT-qPCR)技术检测所有对象血清miR-124表达水平,采用酶联免疫吸附试验(ELISA)检测血清CD146、Angptl2水平,采用单因素及多因素Logistic回归分析ACI患者CAS斑块不稳定的影响因素;采用受试者工作特征(ROC)曲线分析血清miR-124、CD146联合Angptl2对ACI患者CAS斑块不稳定的预测价值。结果ACI组血清CD146、Angptl2水平高于对照组,miR-124表达水平低于对照组(P<0.05)。单因素分析结果显示,ACI患者CAS斑块的稳定性与患者年龄、合并高血压、合并高脂血症、纤维蛋白原(FIB)、血清C反应蛋白(CRP)、血清胱抑素C(CyC)、CD146、Angptl2、miR-124有关(P<0.05);多因素Logistic回归分析结果显示,血清miR-124下降、CD146升高、Angptl2升高、合并高脂血症是ACI患者CAS斑块稳定性的危险因素(P<0.05)。血清miR-124、CD146、Angptl2及三项指标联合应用预测ACI患者CAS斑块不稳定的ROC曲线下面积(AUC)分别为0.741、0.719、0.781和0.834。结论血清miR-124表达水平及CD146、Angptl2水平是ACI患者CAS斑块不稳定的影响因素,可能参与ACI患者CAS斑块形成及发展过程,三者联合检测对ACI患者CAS斑块不稳定具有较好的预测效能。

超重/肥胖合并2型糖尿病患者血清ANGPTL4、HSP70、IL-34水平与胰岛素抵抗的相关性

目的 探讨超重/肥胖合并2型糖尿病(T2DM)患者血清血管生成素样蛋白4(ANGPTL4)、热休克蛋白(HSP)70、白细胞介素-34(IL-34)水平与胰岛素抵抗的相关性。方法 选取2020年5月—2022年5月保定市第一中心医院T2DM患者182例(T2DM组)。参考相关诊断标准,将T2DM患者分为超重/肥胖T2DM组(90例)和体重正常T2DM组(92例)。另选取同期健康体检者90名作为正常对照组,其中超重/肥胖者40名(超重/肥胖对照组)、体重正常者50名(体重正常对照组)。检测所有研究对象血清ANGPTL4、HSP70、IL-34、胰岛素和血糖水平,计算稳态模型胰岛素抵抗指数(HOMA-IR)。T2DM患者治疗3个月后,再次检测其血清ANGPTL4、HSP70、IL-34水平和HOMA-IR。采用Pearson相关分析评估血清ANGPTL4、HSP70、IL-34与HOMA-IR的相关性。结果 与正常对照组和体重正常T2DM组比较,超重/肥胖T2DM组血清ANGPTL4和HSP70显著降低(P<0.05),血清IL-34和HOMA-IR显著升高(P<0.05)。与正常对照组比较,体重正常T2DM组血清ANGPTL4和HSP70显著降低(P<0.05),血清IL-34和HOMA-IR显著升高(P<0.05)。Pearson相关分析结果显示,血清ANGPTL4、HSP70与HOMA-IR呈负相关(r值分别为-0.733、-0.758,P<0.001),IL-34和HOMA-IR呈正相关(r=0.705,P<0.001)。治疗后,超重/肥胖T2DM组和体重正常T2DM组血清ANGPTL4和HSP70均明显升高,血清IL-34和HOMA-IR明显降低;且相对于超重/肥胖T2DM组,体重正常T2DM组血清ANGPTL4和HSP70升高更显著(P<0.05),血清IL-34和HOMA-IR降低更显著(P<0.05)。结论 超重/肥胖合并T2DM患者ANGPTL4、HSP70和IL-34与胰岛素抵抗显著相关,或可作为超重/肥胖合并T2DM的疗效监测指标。

急性心肌梗死患者血清ANGPTL8、KLF2表达与冠脉病变程度及主要心脏不良事件发生的关系

目的探讨急性心肌梗死(AMI)患者血清血管生成素样蛋白8(ANGPTL8)、Kruppel样因子2(KLF2)表达与冠脉病变程度及主要心脏不良事件(MACE)发生的关系。方法选取106例AMI患者为研究对象,根据冠脉病变程度将患者分为轻度组(52例)和重度组(54例),根据MACE发生情况将患者分为MACE组(18例)和非MACE组(88例)。收集患者一般资料,酶联免疫吸附试验(ELISA)法检测血清ANGPTL8、KLF2水平,Spearman相关分析AMI患者血清ANGPTL8、KLF2水平与Gensini评分的相关性,多因素Logistic回归分析AMI患者冠脉病变程度的影响因素;绘制受试者工作特征(ROC)曲线分析血清ANGPTL8、KLF2水平预测AMI患者发生MACE的价值。结果重度组AMI患者高血压史、高血脂史患者比例,收缩压、舒张压、三酰甘油(TG)、N-末端B型利钠肽原(NT-proBNP)、心肌肌钙蛋白I(cTnI)水平,Gensini评分以及血清ANGPTL8水平高于轻度组(P<0.05),高密度脂蛋白胆固醇(HDL-C)水平以及血清KLF2水平低于轻度组(P<0.05);且轻度组和重度组AMI患者病变支数比较,差异有统计学意义(P<0.05)。AMI患者血清ANGPTL8水平与Gensini评分呈正相关(r=0.638,P<0.05),血清KLF2水平与Gensini评分呈负相关(r=-0.612,P<0.05)。高血压史、高血脂史、cTnI、ANGPTL8是AMI患者冠脉病变进展为重度的危险因素(P<0.05),而HDL-C、KLF2是保护因素(P<0.05)。MACE组血清ANGPTL8水平高于非MACE组(P<0.05),而血清KLF2水平低于非MACE组(P<0.05)。血清ANGPTL8、KLF2水平及二者联合预测AMI患者发生MACE的曲线下面积分别为0.740(95%CI:0.646~0.820)、0.799(95%CI:0.710~0.870)、0.806(95%CI:0.717~0.876)。结论血清ANGPTL8、KLF2表达均与AMI患者冠脉病变程度密切相关,且对MACE发生具有一定预测价值。

母体血清GDF-15、ANGPTL8对胎儿先天性心脏病产前诊断的临床意义

目的探讨血清生长分化因子-15(GDF-15)、血管生成素样蛋白8(ANGPTL8)在先天性心脏病(CHD)胎儿母体中的表达及其诊断胎儿CHD的价值。方法收集2020年1月—2023年3月甘肃省妇幼保健院产前诊断中心产前筛查疑似胎儿CHD的120例孕妇作为研究对象,根据产前彩色多普勒超声心动图诊断结果分为CHD组(n=86)和非CHD组(n=34)。比较2组血清GDF-15、ANGPTL8水平;多因素Logistic回归分析胎儿CHD发病的影响因素;ROC曲线分析血清GDF-15、ANGPTL8对胎儿CHD的诊断效能。结果与非CHD组比较,CHD组血清GDF-15、ANGPTL8水平显著升高(t/P=7.860/<0.001、7.334/<0.001);多因素Logistic回归分析结果显示,孕次≥3次、CHD家族史及血清GDF-15、ANGPTL8升高均是胎儿CHD发病的危险因素[OR(95%CI)=1.383(1.082~1.767),1.596(1.148~2.218),3.596(1.694~7.633),3.175(1.571~6.417)];血清GDF-15、ANGPTL8及二者联合预测胎儿CHD的AUC分别为0.805、0.835、0.903,二者联合诊断胎儿CHD优于血清GDF-15、ANGPTL8各自单独诊断(Z=2.052、2.219,P=0.040、0.027)。结论CHD胎儿的母体血清GDF-15、ANGPTL8水平显著升高,二者联合对胎儿CHD具有较高的辅助诊断潜能。

基于倾向性评分匹配探讨妊娠早期空腹血清ANGPTL-2及ANGPTL-8水平预测妊娠期糖尿病的价值

目的:探讨孕妇妊娠早期血清血管生成素样蛋白2(angiopoietin-like protein-2,ANGPTL-2)及ANGPTL-8水平预测妊娠期糖尿病(gestational diabetes mellitus,GDM)的价值。方法:前瞻性收集2023年7—12月在临海市妇幼保健院产检的妊娠早期(10~13周)孕妇共135例,并采集静脉血,根据纳入排除标准最终纳入114例孕妇。根据妊娠24~28周口服葡萄糖耐量试验(oral glucose tolerance test,OGTT)结果,分为GDM组(15例)和对照组(99例)。按照孕妇年龄和产次,采用倾向性评分匹配(1∶1),共配对成功14对(即GDM组14例,对照组14例)。比较2组孕妇血清ANGPTL-2及ANGPTL-8蛋白水平,Pearson相关分析这2种蛋白水平与孕妇临床指标的相关性,受试者工作特征(receiver operating characteristic,ROC)曲线分析2种蛋白对GDM的预测价值。结果:GDM组孕妇血清ANGPTL-2及ANGPTL-8水平均高于对照组(均P<0.05)。Pearson相关分析表明,ANGPTL-2及ANGPTL-8与OGTT时空腹血糖水平呈正相关(r=0.537,P=0.003;r=0.394,P=0.038)。ROC曲线分析显示,ANGPTL-2和ANGPTL-8预测GDM发生的曲线下面积(area under the curve,AUC)分别为0.75(95%CI:0.57~0.93)、0.79(95%CI:0.61~0.97),二者联合预测的AUC为0.81(95%CI:0.65~0.97)。结论:妊娠早期血清ANGPTL-2和ANGPTL-8水平可作为GDM的早期预测指标,有助于促进GDM的早期识别和干预管理。

血清Betatrophin、ANGPTL4预测GDM患者不良妊娠结局价值

目的:探讨促代谢因子(Betatrophin)、血管生成素样蛋白4(ANGPTL4)联合预测妊娠期糖尿病(GDM)患者不良妊娠结局价值。方法:回顾性收集2019年10月-2022年9月本院分娩的GDM患者128例为GDM组、健康孕妇128例为对照组,比较两组血清Betatrophin、ANGPTL4水平及妊娠结局。logistic回归分析GDM患者不良妊娠结局的影响因素;受试者工作特征(ROC)曲线分析血清Betatrophin、ANGPTL4对GDM患者妊娠结局的预测价值。结果:GDM组血清Betatrophin水平(390.27±65.05pg/ml)及不良妊娠结局发生率(34.4%)高于对照组(291.56±48.59pg/ml、8.6%),ANGPTL4水平(4.23±1.40 ng/ml)低于对照组(8.22±2.74 ng/ml),GDM妊娠结局不良组糖尿病家族史占比、血清Betatrophin水平高于结局良好组,ANGPTL4水平低于妊娠结局良好组,糖尿病家族史、Betatrophin较高、ANGPTL4较低是GDM患者不良妊娠结局的危险因素(均P<0.05)。血清Betatrophin、ANGPTL4预测GDM患者不良妊娠结局的曲线下面积(AUC)分别为0.864、0.877,联合预测AUC(0.968)提高,其灵敏度97.7%、特异度85.7%。结论:GDM患者血清Betatrophin水平较高、ANGPTL4水平较低,是不良妊娠结局发生危险因素,2项指标联合检测预测GDM患者不良妊娠结局价值较好。

冠状动脉CT血管造影及血清指标对冠心病冠状动脉狭窄程度的评价

目的:探讨冠状动脉CT血管造影(CCTA)及血清脂蛋白相关磷脂酶A2(Lp-PLA2)、血管生成素样蛋白3(ANGPTL3)对冠心病冠状动脉狭窄程度的评价。方法:选取2022年7月至2023年3月河北省胸科医院诊治的102例冠心病患者,按照冠状动脉狭窄程度积分(Gensini积分)情况将其分为轻度组(0分≤Gensini积分≤20分)、中度组(20分<Gensini积分≤60分)及重度组(Gensini积分>60分),每组34例。对比3组患者冠状动脉最小管腔直径(MLD)、狭窄面积百分比(%AS)、狭窄直径百分比(%DS)、最小管腔面积(MLA)、Lp-PLA2及ANGPTL3,根据受试者工作特征(ROC)曲线,预测冠状动脉狭窄程度的诊断效能。结果:重度组MLA、MLD低于中度组和轻度组,而%AS、%DS高于中度组和轻度组,差异有统计学意义(t=6.905、4.083、5.871、6.976、3.387、2.198、2.668、3.505,P<0.05)。重度组Lp-PLA2、ANGPTL3高于中度组和轻度组,差异有统计学意义(t=4.164、8.220、2.575、3.050,P<0.05)。ROC曲线分析显示,MLA、MLD、%AS、%DS、CCTA综合参数、LpPLA2以及ANGPTL3预测冠状动脉狭窄程度的ROC曲线下面积(AUC)值分别为0.838、0.690、0.742、0.801、0.904、0.808和0.807。灵敏度分别为91.20%、91.20%、64.70%、94.10%、97.10%、70.60%和88.20%;特异度分别为76.50%、57.40%、75.00%、50.00%、70.60%、97.10%和70.60%。CCTA综合参数的AUC分别高于LpPLA2和ANGPTL3,但差异无统计学意义(P>0.05)。结论:CCTA及血清Lp-PLA2、ANGPTL3评估冠心病冠状动脉狭窄程度均具有一定效能,且CCTA的预测效能更高。