The purpose of this study is to
Determine blood peptide levels and investigate any tissue gradients of apelin in patients with idiopathic pulmonary arterial hypertension and healthy volunteers.
Evaluate the effect of exogenous apelin infusion on exercise performance in healthy volunteers and patients with idiopathic pulmonary arterial hypertension.

开始日期2012-03-01

申办/合作机构

Imperial College London

100 项与 Apelin-13 相关的临床结果

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100 项与 Apelin-13 相关的转化医学

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100 项与 Apelin-13 相关的专利（医药）

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377

项与 Apelin-13 相关的文献（医药）

2024-12-04·NeuroReport

The effects of apelin-13 in a mouse model of post-traumatic stress disorder

Article

作者: Meng, Zijun ; Kuai, Jinxia ; Han, Yuqing ; Yang, Xiaofang ; Bao, Haijun ; Zhou, Yang

The objective is to investigate the effects of apelin-13 in models of post-traumatic stress disorder (PTSD). Mature male CD1 mice were subjected to the single prolonged stress method to induce PTSD-related behaviors. These behaviors were then evaluated using the elevated plus maze test, Morris water maze test, and open field test. Hippocampal neural cell death was assessed using propidium iodide labeling. The expression of hippocampal autophagy pathway-associated proteins was determined through immunoblotting analysis, and LC3 levels were also measured via quantitative real-time reverse transcription-PCR. The results demonstrate that administration of apelin-13 suppressed PTSD-induced hippocampal neural cell death and alleviated PTSD-related behaviors in mice. Additionally, PTSD led to an up-regulation of LC3 and FoxO3a, and down-regulation of P62, p-PI3K, p-Akt, and p-FoxO3a in the hippocampus. However, these changes were reversed by apelin-13 treatment. These findings support the hypothesis that apelin-13 prevents the development of PTSD-like behavior and inhibits autophagy of neuronal cells in a mouse model of PTSD. Apelin-13 may hold potential as a therapeutic agent for PTSD in clinical applications.

2024-12-01·Molecular Biology Reports

Protective effect of apelin-13 on ventilator-induced acute lung injury

Article

作者: Zhou, Leilei ; Lian, Siyu ; Jiang, Wenqing ; Chen, Zongyu ; He, Shuang ; Zhang, Xianming ; Shen, Yi

BACKGROUNDMechanical Ventilation (MV) is an essential mechanism of life support in the clinic. It may also lead to ventilator-induced acute lung injury (VILI) due to local alveolar overstretching and/or repeated alveolar collapse. However, the pathogenesis of VILI is not completely understood, and its occurrence and development may be related to physiological processes such as the inflammatory response, oxidative stress, and apoptosis. Some studies have found that the the apelin/APJ axis is an endogenous antagonistic mechanism activated during acute respiratory distress syndrome(ARDS), that can counteract the injury response and prevent uncontrolled lung injury. To indicate that apelin-13 plays a protective role in VILI, an animal model of VILI was established in this study to explore whether apelin-13 can alleviate VILI in rats by inhibiting inflammation, apoptosis and oxidative stress.METHODSSD rats were divided into four groups: control, high tidal volume, high tidal volume + normal saline and high tidal volume + apelin-13. After tracheotomy, the rats in control maintained spontaneous breathing, and the other rats were connected to the small animal ventilator for 4 h to establish the rat VILI model. The mRNA expression of apelin was measured by real-time quantitative polymerase chain reaction(qRT-PCR), immunofluorescence and Western blotting(WB) were used to detect the expression level of APJ, and WB was used to detect the expression of the apoptotic proteins Bax and bcl-2. The degree of lung injury was evaluated by pathological staining of lung tissue,W/D ratio, and BALF total protein concentration. The expression of inflammatory factors(IL-1β, IL-6, TNF-α) in alveolar lavage fluid was measured using ELISA. The activities of MPO and cat and the content of MDA, an oxidative product, in lung tissue were measured to evaluate the degree of oxidative stress in the lung.RESULTSAfter treatment with apelin-13, the apelin/APJ axis in the lung tissue of VILI model rats was activated, and the effect was further enhanced. The pathological damage of lung tissue was alleviated, the expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax was reversed, and the levels of the inflammatory cytokines IL-1β, IL-6, TNF-α levels were all decreased. MPO activity and MDA content decreased, while CAT activity increased.CONCLUSIONThe apelin/apj axis is activated in VILI. Overexpression of apelin-13 further plays a protective role in VILI, mainly by including reducing pathological damage, the inflammatory response, apoptosis and antioxidant stress in lung tissue, thus delaying the occurrence and development of VILI.

2024-11-01·Neuroscience Letters

Effects of Apelin-13 on auditory system in STZ-induced diabetic rats

Article

作者: Kılınç, Sevtap ; Eylül Aydemir, Berfin ; Arzu Yiğit, Ayşe ; Güneşer, Özgecan ; Ölçüoğlu, Rukiye ; Kilinç, Sevtap

AIMDamage to the auditory pathways is one of the complications of diabetes. The aim of this study was to investigate the potential therapeutic effects of apelin-13 in the auditory pathways of rats with experimentally induced diabetes by examining its effect on auditory brainstem responses, cochlear oxidative stress and inflammatory cytokines.METHODSThirty-two male Wistar albino rats were divided into four groups: sham control, diabetes, apelin and diabetes + apelin. A single dose of 45 mg/kg streptozotocin (STZ) was administered to induce diabetes. The apelin group received 50 µg/kg apelin-13 for seven days intraperitoneally (ip). At the end of the apelin and STZ applications auditory brainstem responses (ABR) was recorded. At the end of the experiment, cochlea was removed and biochemical analyzes were performed.RESULTSIn ABR recordings, the latencies of wave V in diabetic group were observed to be longer than those of the control, with the apelin treatment exhibiting a partial reversal of this situation, particularly at specific frequencies and intensity levels. Apelin treatment leads to a significant increase in total antioxidant status (TAS) and a reduction in total oxidant status (TOS) and oxidative stress index (OSI) in cochlea compared to diabetic groups. The levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL-1 beta) in cochlear tissue were found to be significantly reduced in the apelin-treated group compared to the diabetic group.CONCLUSIONApelin-13 may have a protective effect on the auditory system and may be proposed as a potential new therapeutic strategy for the management diabetic auditory impairment.

项与 Apelin-13 相关的新闻（医药）

2024-03-01

·生物探索

Cell | 浙江大学张岩等团队合作揭示受体结构助力心脏病药物

引言Apelin（爱帕琳肽）是心血管稳态的关键激素，可激活Apelin受体(APLNR)，被认为是心血管疾病的一个有前景的治疗靶点。然而，通过β-抑制素途径产生的不良反应限制了其药理应用。2024年2月29日，浙江大学张岩及北京大学张岩共同通讯在Cell 在线发表题为“Structure-based design of non-hypertrophic apelin receptor modulator”的研究论文，该研究报告了与三种具有不同信号谱的激动剂结合的APLNR-Gi1复合物的冷冻电镜(cryo-EM)结构。结合功能分析，作者确定了APLNR中的“双热点”是信号偏倚的关键决定因素，指导了两种独家G蛋白偏倚激动剂WN353和WN561的合理设计。WN353-和WN561刺激的APLNR-G蛋白复合物的cryo-EM结构进一步证实了所设计的配体具有所需的姿态。病理生理实验证明，与已建立的APLNR激动剂相比，WN561对心脏肥厚的治疗效果更好，不良反应更少。该研究设计的APLNR调节剂可能促进下一代心血管药物的开发。心肌肥大的特征是心肌质量增加，是对病理性刺激(如高血压和瓣膜疾病)的适应性反应。虽然最初是有益的，但持续的肥厚可能导致疾病进一步进展并加剧心力衰竭，心力衰竭是世界上最常见和最致命的疾病之一，并且仍然无法治愈。抑制或逆转心肌肥厚和随后的不适应心肌重构是心力衰竭的主要治疗方法。心肌细胞肥大可由多种内在和外在刺激触发，包括机械应力和激素，这些刺激可通过一系列细胞膜受体被心肌细胞识别G蛋白偶联受体(GPCRs)，在启动肥厚信号通路和调节健康和患病状态下的心脏功能方面至关重要。广泛的GPCR拮抗剂已用于治疗心力衰竭，包括靶向β-肾上腺素能受体、血管紧张素II受体和醛固酮受体的拮抗剂。由于疗效不足和不良反应，只有少数治疗心血管疾病，特别是治疗心力衰竭的药物有改善生活质量、身体功能或症状的指征。因此，有必要确定新的治疗靶点和策略来对抗心力衰竭。Apelin受体APJ是一种典型的A类GPCR，在心血管系统中起着至关重要的作用。APLNR的多种生理作用包括促进心脏收缩力、增加左室卒中容量、血管舒张、促进利尿、降低体血压。apelin/APLNR系统也参与心血管疾病的病理生理，如心力衰竭和肺动脉高压，使其成为一个有希望的治疗靶点。Apelin是APLNR的内源性配体，作为平衡激动剂激活APLNR的G蛋白和β-阻滞蛋白途径。有研究提出，apelin诱导的心脏保护作用主要归因于APLNR的Gi信号传导，而APLNR的β-骤停素途径导致有害的心脏肥厚。因此，人们对开发G蛋白偏倚的APLNR激动剂作为治疗心力衰竭的潜在药物越来越感兴趣。已经发现了几种部分G蛋白偏倚的APLNR激动剂，尽管与apelin相比G蛋白活性降低，但在大鼠和人类中均表现出优越的心血管作用。特别是，MM07是一种G蛋白偏倚肽激动剂，通过用半胱氨酸取代apelin中的位置1和6而产生二硫键，而CMF-019是一种G蛋白偏倚的APLNR小分子激动剂。然而，尽管这些配体的低但保留的β-阻滞蛋白信号仍然是其安全临床应用的主要障碍，强调迫切需要开发真正的G蛋白偏向激动剂，在保持完整的G蛋白信号的同时消除β-阻滞蛋白信号活性。模式图（Credit: Cell）该研究首先用三种激动剂([Pyr1]-apelin-13(简称apelin)， MM07和CMF-019)解析了aplnn-Gi1复合物的高分辨率冷冻电镜(cryo-EM)结构。这些结构揭示了不同的配体结合特性，以及强调APLNR偏置信号的分子机制。基于这些发现，作者设计了G蛋白偏向激动剂WN353和WN561，它们几乎消除了β-阻滞蛋白活性，同时保持了G蛋白信号传导能力。解决WN353-和wn561结合的aplnn-Gi1复合物的两个冷冻电镜结构使得能够了解APLNR中偏倚信号传导的机制。体外和体内病理生理研究证实，所鉴定的G蛋白偏倚激动剂WN561在促进G蛋白信号传导心脏保护功能的同时，减少β-阻滞蛋白活性潜在的肥厚不良反应，具有良好的应用前景。原文链接https://www.cell.com/cell/abstract/S0092-8674(24)00125-9责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文Nature | 癌症与神经系统的致命舞蹈

100 项与 Apelin-13 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
2型糖尿病	临床1期	-	Le Centre Hospitalier Universitaire de Toulouse	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


Pubmed \| J Mol Biol	N/A	-	-	Apelin-13	(壓網簾壓膚積壓鹽選壓) = Apelin also increased I(Na) "window" current by up to 600% 獵範網窪網網餘艱鹽積 (鑰顧憲鹽遞衊築膚襯遞 )	-	2010-04-01
				Apelin-17