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elabela is a reliable biomarker for predicting early onset preeclampsia:A comparative study

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World Journal of Clinical Cases 2023年第17期11卷 3993-4002页

作者： Eham Amer Ali Wassan Nori Alea Farhan Salman Taghreed S Saeed Al-Rawi Ban H Hameed Raid M Al-Ani Department of Chemistry and Biochemistry Mustansiriyah UniversityBaghdad 10052Iraq Department of Obstetrics and Gynecology Mustansiriyah UniversityBaghdad 10052Iraq National Central of Hematology Mustansiriyah UniversityBaghdad 10052Iraq Department of Biochemistry University of Anbar College of MedicineRamadi City 31001AnbarIraq Department of Surgery/Otolaryngology University of Anbar College of MedicineUniversity of Anbar College of MedicineRamadi City 31001AnbarIraq

BACKGROUND Preeclampsia(PE)is a multisystemic metabolic disease with an undetermined etiology.PE is a worldwide cause of maternal and perinatal morbidity,subdivided into early(EoPE)and late-onset(LoPE)according to 34 wk of gestation as a divider.Many researchers investigated biomarkers for predicting PE to halt its consequences on the feto-maternal outcome.elabela(Ela)is a newly discovered peptide hormone that was implicated in PE pathogenesis.Earlier rodent studies discussed Ela’s role in controlling blood pressure.Moreover,Ela deficiency was associated with PE development.AIM To test whether plasma Ela could serve as a reliable marker for predicting PE based on the time of onset(EoPE vs LoPE)compared to age and body mass matched healthy controls since no definitive treatment exists for PE but to terminate a pregnancy.METHODS This case-control study recruited(n=90)pregnant who fulfilled inclusion criteria;they were allocated into three groups:EoPE(30/90)(9.156 with 96.7%and 93.3%sensitivity and specificity,P<0.0001 in predicting EoPE.CONCLUSION A strong correlation of serum Ela with PE parameters with excellent sensitivity and specificity in distinguishing EoPE independent of the BMI,age,and blood pressure which makes Ela a recommendable marker in

关键词： Early onset preeclampsia Late-onset preeclampsia Prediction elabela Preeclampsia Pregnant women

Targeting the elabela/apelin-apelin receptor axis as a novel therapeutic approach for hypertension

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Chinese Medical Journal 2022年第9期135卷 1019-1026页

作者： Jiawei Song Jianqiong Tang Zhenzhou Zhang Ying Liu Jiuchang Zhong Heart Center and Beijing Key Laboratory of Hypertension Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China Department of Critical Care Medicine Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 201600China Beijing Institute of Respiratory Medicine Beijing 100020China.

Hypertension is the leading risk factor for global mortality and morbidity and those with hypertension are more likely to develop severe symptoms in cardiovascular and cerebrovascular system,which is closely related to abnormal renin-angiotensin system and elabela/apelin-apelin receptor(APJ)axis.The elabela/apelin-APJ axis exerts essential roles in regulating blood pressure levels,vascular tone,and cardiovascular dysfunction in hypertension by counterbalancing the action of the angiotensin II/angiotensin II type 1 receptor axis and enhancing the endothelial nitric oxide(NO)synthase/NO signaling.Furthermore,the elabela/apelin-APJ axis demonstrates beneficial effects in cardiovascular physiology and pathophysiology,including angiogenesis,cellular proliferation,fibrosis,apoptosis,oxidative stress,and cardiovascular remodeling and dysfunction during hypertension.More importantly,effects of the elabela/apelin-APJ axis on vascular tone may depend upon blood vessel type or various pathological conditions.Intriguingly,the broad distribution of elabela/apelin and alternative isoforms implicates its distinct functions in diverse cardiac and vascular cells and tissue types.Finally,both loss-of-function and gain-of-function approaches have defined critical roles of the elabela/apelin-APJ axis in reducing the development and severity of hypertensive diseases.Thus,targeting the elabela/apelin-APJ axis has emerged as a pre-warning biomarker and a novel therapeutic approach against progression of hypertension,and an increased understanding of cardiovascular actions of the elabela/apelin-APJ axis will help to develop effective interventions for hypertension.In this review,we focus on the physiology and biochemistry,diverse actions,and underlying mechanisms of the elabela/apelin-APJ axis,highlighting its role in hypertension and hypertensive cardiovascular injury and dysfunction,with a view to provide a prospective strategy for hypertensive disease therapy.

关键词： elabela Apelin APJ Hypertension Renin-angiotensin system

elabela通过调节水通道蛋白2改善糖尿病肾病作用及机制研究

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中华内分泌代谢杂志 2022年第8期38卷 651-657页

作者：石敏徐玉迪王子葳宋婧张红南京医科大学附属淮安第一医院内分泌科 223300

目的观察elabela(Ela)对糖尿病肾病(DKD)保护作用及可能机制。方法db/db小鼠随机分为糖尿病组和Ela干预组,db/m小鼠为正常对照组。Ela干预组小鼠腹腔注射Ela-215 mg·kg^(-1)·d^(-1),持续8周。实验结束测尿白蛋白/肌酐比值(UACR)等代... 详细信息

目的观察elabela(Ela)对糖尿病肾病(DKD)保护作用及可能机制。方法db/db小鼠随机分为糖尿病组和Ela干预组,db/m小鼠为正常对照组。Ela干预组小鼠腹腔注射Ela-215 mg·kg^(-1)·d^(-1),持续8周。实验结束测尿白蛋白/肌酐比值(UACR)等代谢指标,HE染色和PAS染色观察肾脏病理学改变,免疫组化观察水通道蛋白2(AQP2)表达,Western blot分析肾脏Ⅳ型胶原蛋白(Col-Ⅳ)和AQP2水平。Ela处理高糖诱导人肾小管上皮细胞(HK-2),Western blot观察HK2细胞外基质主要成分Col-Ⅳ及AQP2的表达;进一步敲除HK2细胞apelin受体(APJ),观察Ela的干预效应。最后,利用NanoBit?技术,研究Ela诱导的APJ激活与抗利尿激素(AVP)诱导的抗利尿激素2型受体(AVPR2)活化间的相互作用,以明确Ela调节AQP2的可能机制。结果(1)在不影响血糖、体重等代谢指标的情况下,Ela干预明显降低了db/db小鼠的UACR水平,且肾脏病理损害显著改善,肾组织Col-Ⅳ水平下降,AQP2表达明显降低。(2)Ela干预可明显抑制高糖诱导的Col-Ⅳ表达和AQP2水平,进一步干扰APJ后,Ela对Col-Ⅳ和AQP2调节作用被逆转。(3)Ela激活APJ可明显拮抗AVP诱导的AVPR2下游信号β-Arrestin-2(ARRB2)传递,进一步提示Ela对AQP2的抑制作用可能与拮抗AVP/AVPR2信号有关。结论Ela可能通过APJ介导作用,抑制AQP2水平,发挥DKD保护作用。

关键词： elabela 糖尿病肾病水通道蛋白2

Plasma levels of elabela are associated with coronary angiographic severity in patients with acute coronary syndrome

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Journal of Geriatric Cardiology 2020年第11期17卷 674-679页

作者： Sheng-Li DU Xin-Chun YANG Jiu-Chang ZHONG Le-Feng WANG Yi-Fan FAN Heart Center and Beijing Key Laboratory of Hypertension Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina

Background elabela(ELA) was newly discovered as a novel endogenous ligand of the apelin receptor(APJ) which has demonstrated to be crucial for cardiovascular disease such as myocardial infarction, hypertension and heart failure. Previous experiments have revealed that ELA reduced arterial pressure and exerted positive inotropic effects on the heart. However, the role of plasma ELA levels in patients with acute coronary syndrome(ACS) and its relationship with severity of coronary arteries have not been investigated. Methods Two hundred and one subjects who were hospitalized for chest pain and underwent coronary angiography were recruited in this study. One hundred and seventy five patients were diagnosed with ACS and twenty-six subjects with negative coronary angiography were included in the control group. Plasma ELA levels, routine blood test, blood lipid, liver and kidney functions were measured. The number of coronary arteries and SYNTAX(Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score of coronary lesions were used to evaluate the extent of coronary artery stenosis. Results ELA in patients with ACS was significantly higher than that in the control group(P < 0.01). There was no significant difference in plasma ELA levels among patients with single-, double-and triple-vessel diseases. However, in the generalized additive model(GAM), there was a threshold nonlinear correlation between the ELA levels and Syntax I score(P < 0.001). Plasma ELA levels were positively correlated with the Syntax I score when the ELA levels ranged from 63.47 to 85.49 ng/m L. There was no significant association between the plasma ELA levels and the extent of coronary artery stenosis when the ELA levels were less than 63.47 ng/m L or higher than 85.49 ng/m L. Conclusion The present study demonstrates for the first time that plasma ELA levels are increased in patients with ACS. The rise in endogenous ELA levels was associated with severity of coronary stenosis and may be involved in the pathogenesis

关键词： Acute coronary syndrome Coronary artery stenosis elabela

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elabela促进心肌梗死运动康复机制

生命科学 2023年第3期35卷 352-359页

作者：潘收席悦田振军陕西师范大学体育学院暨运动生物学研究所西安710119

G蛋白偶联受体Apelin receptor(APLNR,APJ)早期配体elabela/Toddler/Apela(ELA)是一种肽类激素,对心血管系统早期发育必不可少。心肌梗死(myocardial infarction,MI)后,ELA表达代偿性升高,外源性ELA干预具有靶向抑制氧化应激、细胞凋亡并促进心肌新生、抵抗MI所致心衰的作用,对改善病理心脏重塑和提升心功能等效果显著。运动可促进内源性ELA发挥MI心脏的保护作用。现对ELA结合运动干预改善氧化应激引起的细胞凋亡并缓解缺血心脏功能障碍等文献进行梳理,提出运动促进MI心脏功能改善与康复的新观点,从而为MI患者临床度过急性期后进行运动康复研究提供有价值的理论依据。

关键词：心肌梗死 elabela 运动氧化应激细胞凋亡

利用Crispr/Cas9基因编辑系统在人胚胎干细胞中探索elabela的潜在新受体

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上海交通大学学报（医学版） 2022年第9期42卷 1258-1264页

作者：周月程晨郑恩霖孟卓王鉴王青洁何勇宁孙锟上海交通大学医学院附属新华医院小儿心血管科上海200092 上海交通大学医学院附属仁济医院上海肿瘤研究所上海200127

目的·利用Crispr/Cas9基因编辑技术在人胚胎干细胞(human embryonic stem cell,hESC)中探索小分子多肽elabela(ELA)是否存在潜在的新受体。方法·收集干细胞向心肌细胞定向分化过程中不同天数(0~13 d)的细胞,检测其ELA及其受体APJ的动... 详细信息

目的·利用Crispr/Cas9基因编辑技术在人胚胎干细胞(human embryonic stem cell,hESC)中探索小分子多肽elabela(ELA)是否存在潜在的新受体。方法·收集干细胞向心肌细胞定向分化过程中不同天数(0~13 d)的细胞,检测其ELA及其受体APJ的动态表达水平。在干细胞向心肌细胞定向分化过程中加入APJ抑制剂ML221,观察心肌细胞标志物MYH6、TnnT2及NKX2.5的mRNA表达水平是否发生变化。利用人胚肾悬浮细胞(HEK-293F)表达重组ELA绿色荧光蛋白(green fluorescent protein,GFP),研究ELA发挥结合作用的区域在其C末端还是N末端,构建GFP序列分别插入ELA-32序列的C末端及N末端的2种重组质粒。利用Crispr/Cas 9基因编辑技术构建ELA唯一已知受体APJ敲除的hESC并进行验证。在构建成功的敲除细胞系及正常细胞系中外源性加入2种GFP-ELA重组蛋白,通过荧光显微镜观察ELA是否能够进入细胞。结果·在干细胞向心肌细胞定向分化过程中,在干细胞时期,ELA高表达而APJ低表达;ELA表达高峰在分化第6天而APJ表达高峰出现在分化第3天。外源性加入APJ抑制剂ML221后,MYH6、TnnT2及NKX2.5的mRNA表达水平无显著变化(P>0.05)。经过基因DNA测序及Western blotting验证,成功构建敲除APJ干细胞系。敲除APJ后,外源性加入ELA N端荧光蛋白,仍能够进入细胞内;而ELA C端荧光蛋白未出现荧光,表示ELA C端荧光蛋白不能进入细胞。结论·hESC中存在非APJ的ELA其他受体,ELA与受体发生结合的部位主要位于C末端。

关键词：人胚胎干细胞 elabela APJ 基因编辑

血浆elabela水平预测大血管闭塞型急性缺血性脑卒中患者血管内机械取栓术后近期预后的临床研究

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中华神经医学杂志 2023年第12期22卷 1242-1247页

作者：陈浪李瑞殷亚美罗聪蒿鹏丰硕蔡明孙俊胡伟安徽医科大学附属省立医院神经内科合肥230001

目的探讨大血管闭塞型急性缺血性脑卒中(LVO-AIS)患者接受血管内机械取栓术(EVT)后3个月预后和血浆elabela水平的关系。方法前瞻性选取安徽医科大学附属省立医院神经内科自2020年8月至2022年8月采用EVT治疗的94例LVO-AIS患者。术前、术... 详细信息

目的探讨大血管闭塞型急性缺血性脑卒中(LVO-AIS)患者接受血管内机械取栓术(EVT)后3个月预后和血浆elabela水平的关系。方法前瞻性选取安徽医科大学附属省立医院神经内科自2020年8月至2022年8月采用EVT治疗的94例LVO-AIS患者。术前、术后24 h和术后72 h采用ELISA法检测患者血浆elabela水平,术后3个月采用改良Rankin量表(mRS)评估患者的预后。比较预后良好组与预后不良组患者临床资料、血浆elabela水平的差异,采用多因素Logistic回归分析明确LVO-AIS患者术后3个月预后的独立影响因素,采用受试者工作特征(ROC)曲线分析血浆elabela水平对LVO-AIS患者术后3个月预后的预测效能。结果与预后不良组比较,预后良好组患者有脑卒中史、糖尿病者占比较低,入院时美国国立卫生研究院卒中量表(NIHSS)评分较低,差异均有统计学意义(Pelabela水平高于预后不良组患者,差异有统计学意义(Pelabela水平(OR=1.064,P=0.005,95%CI:1.019~1.111)是LVO-AIS患者术后3个月预后的独立影响因素。ROC曲线分析显示,术后72 h血浆elabela水平预测LVO-AIS患者术后3个月预后的ROC曲线下面积(AUC)为0.718(Pelabela水平可能是预测LVO-AIS患者EVT术后近期预后的潜在生物标志物。

关键词：急性缺血性脑卒中血管内机械取栓术 elabela 预后生物标志物

elabela活性片段ELA14在对比剂致大鼠肾小管上皮细胞凋亡中的作用机制

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医学研究生学报 2022年第8期35卷 841-846页

作者：孟丹心李益民美合日阿依·约麦尔陆治平黄进南京医科大学附属脑科医院心血管内科南京210029 南京医科大学附属逸夫医院心血管内科南京211166

目的 elabela活性片段ELA32在对比剂肾病中可减轻肾损伤,但ELA14在对比剂肾病中作用仍不明确。文章探究elabela活性片段ELA14在对比剂致大鼠肾小管上皮细胞(NRK-52E细胞)凋亡中作用及机制。方法实验分组:对照组、碘普罗胺(IOP)组(加入2... 详细信息

目的 elabela活性片段ELA32在对比剂肾病中可减轻肾损伤,但ELA14在对比剂肾病中作用仍不明确。文章探究elabela活性片段ELA14在对比剂致大鼠肾小管上皮细胞(NRK-52E细胞)凋亡中作用及机制。方法实验分组:对照组、碘普罗胺(IOP)组(加入21 mgI/mL IOP)、IOP+高、低剂量ELA32组(21 mgI/mL IOP与30 nmol/L、3μmol/L ELA32共同孵育)、IOP+高、低剂量ELA14组(21 mgI/mL IOP与30 nmol/L、3μmol/L ELA14共同孵育)。用流式细胞仪检测细胞凋亡率、CCK-8评估细胞活力,酶联免疫法测定炎症因子,线粒体活性氧法测定ROS强度,Western blot、qRT-PCR检测细胞mRNA和蛋白表达量。结果 IOP组细胞凋亡率[(17.306±0.848)%]较对照组[(4.860±0.182)%]明显升高(P0.05),另外ELA32和ELA14均可改善ROS水平、炎症因子水平及DNA损伤相关蛋白的表达。IOP组细胞荧光强度(3 842.780±444.146)较对照组(240.18±80.941)明显升高,而IOP+高、低剂量ELA32组和IOP+高、低剂量ELA14组细胞荧光强度(807.810±98.798、2 008.460±332.571、1 362.716±415.551、2 325.856±455.404)较IOP组明显减弱(P<0.05)。结论与ELA32相似,ELA14也可抑制IOP诱导的NRK-52E细胞氧化应激、炎症反应及细胞凋亡,并呈剂量依赖性,该作用可能通过抑制氧化炎症反应实现。

关键词： elabela 肾损伤对比剂氧化应激

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elabela与子痫前期发病的关系

ELABELA与子痫前期发病的关系

作者：樊潞潞大连医科大学

学位级别：硕士

目的:通过检测子痫前期及正常妊娠孕妇血清及胎盘中elabela的表达水平明确elabela与子痫前期的发病关系;通过检测胎盘组织中MMP9的表达及分析elabela与MMP9的相关性探讨elabela参与子痫前期的可能机制。方法:选择2020年1月至2021年1月期... 详细信息

目的:通过检测子痫前期及正常妊娠孕妇血清及胎盘中elabela的表达水平明确elabela与子痫前期的发病关系;通过检测胎盘组织中MMP9的表达及分析elabela与MMP9的相关性探讨elabela参与子痫前期的可能机制。方法:选择2020年1月至2021年1月期间,在本部产科因子痫前期剖宫产分娩的孕妇26例为实验组。另选取择期剖宫产的健康孕妇26例为对照组。所选取的孕妇年龄、怀孕周数及身体质量指数(BMI)的比较,差异均无统计学意义(P>0.05);所选入组孕妇均为自然受孕,首次分娩,单活胎,且既往无心血管疾病,糖尿病,肝肾功能异常及心肺功能异常等慢性疾病,无任何不良妊娠史,无不良嗜好;分娩方式均为子宫下段横切口剖宫产术,麻醉方式均为蛛网膜下腔与硬脊膜外联合阻滞。(1)通过酶联免疫吸附试验(Elisa)检测孕妇血清中elabela蛋白的表达水平。(2)通过免疫组化定位胎盘组织中的elabela蛋白;通过荧光定量PCR检测子痫前期组及正常妊娠组胎盘组织中elabela m RNA的表达;通过Western blot检测子痫前期组及正常妊娠组胎盘组织中elabela蛋白的表达。(3)通过荧光定量PCR检测子痫前期组及正常妊娠组胎盘组织中MMP9 m RNA的表达;通过Western blot检测子痫前期组及正常妊娠组胎盘组织中MMP9蛋白的表达。(4)应用统计学软件分析elabela和MMP9的相关性,得出结论。结果:(1)Elisa检测发现子痫前期组血清中elabela蛋白表达明显低于对照组。(2)免疫组化发现elabela主要表达于胎盘细胞滋养层和合体滋养层细胞的胞浆中;相对于对照组来说,子痫前期组胎盘组织中elabela m RNA及elabela蛋白的表达均明显降低,差异具有显著统计学意义(Pelabela蛋白的表达呈正相关,提示elabela可能通过MMP9作用于滋养细胞的侵袭参与子痫前期发病。结论:子痫前期患者血清及胎盘中elabela表达明显降低提示elabela参与子痫前期的发病。子痫前期患者胎盘组织MMP9表达明显降低,且子痫前期组MMP9蛋白和elabela蛋白的表达呈正相关,提示elabela可能通过MMP9影响滋养细胞侵袭参与子痫前期发病。

关键词：子痫前期 elabela APJ MMP9