[Pyr1]Apelin-13 被确定为人类心脏中的主要 Apelin 异构体：血管活性机制和疾病中的肌力作用,Hypertension

当前位置： X-MOL 学术 › Hypertension › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

[Pyr1]Apelin-13 被确定为人类心脏中的主要 Apelin 异构体：血管活性机制和疾病中的肌力作用
Hypertension ( IF 6.9 ) Pub Date : 2009-09-01 , DOI: 10.1161/hypertensionaha.109.134619
Janet J. Maguire ₁ , Matthias J. Kleinz ₁ , Sarah L. Pitkin ₁ , Anthony P. Davenport ₁

Affiliation

存在于血管平滑肌细胞、内皮和心肌细胞上的 Apelin 受体被 Apelin 肽家族激活，从而在实验动物中引发心血管效应，但尚未详细研究人类的功能活性。我们在志愿者血浆中检测到低水平的 apelin 免疫反应性，与自分泌/旁分泌作用一致，并在人培养的内皮细胞上清液中检测到 apelin 免疫反应性。我们发现 [Pyr1]apelin-13 是冠状动脉疾病患者心脏组织中的主要亚型。我们在体外测试了 apelins 在人体组织中具有血管和心脏作用的假设，并比较了对 [Pyr1]apelin-13、apelin-13 和 apelin-36 的反应。在内皮完整的乳腺动脉中，所有 3 种 apelins 均以相当的效力诱导浓度依赖性血管舒张（EC50：0.6 至 1.6 nM；最大响应：40% 至 50%）。血管扩张在去除内皮或与吲哚美辛预孵育后消失，但不受与 NG-硝基-l-精氨酸甲酯预孵育的影响，表明在该患者组中，前列腺素类物质参与了 apelins 的扩张，但没有参与。Apelins 是内皮裸露的隐静脉（EC50：0.6 至 1.6 nM；最大响应：17% 至 26%）和乳腺动脉（[Pyr1]apelin-13；EC50：0.2 nM；最大响应：29%）的有效收缩剂。在起搏心房条带中，所有 3 种肽都以亚纳摩尔效力（EC50：40 至 125 pM）增加收缩力。首次，我们证明了 3 种主要形式的 apelin 在人类心血管组织中具有相当的效力和功效。Apelins 是有效的内皮依赖性血管扩张剂，通过前列腺素依赖性机制起作用；然而，内皮的去除揭示了动脉和静脉中的直接血管收缩作用。此外，在人类心脏组织中，apelin 肽是迄今为止报道的最有效的内源性正性肌力药物之一。

"点击查看英文标题和摘要"

[Pyr1]Apelin-13 Identified as the Predominant Apelin Isoform in the Human Heart: Vasoactive Mechanisms and Inotropic Action in Disease

Apelin receptors, present on vascular smooth muscle cells, endothelium, and cardiomyocytes, are activated by the family of apelin peptides to elicit cardiovascular effects in experimental animals, but functional activity in humans has not been studied in detail. We detected low levels of apelin immunoreactivity in plasma of volunteers consistent with an autocrine/paracrine action and detected apelin immunoreactivity in the supernatant from human cultured endothelial cells. We found that [Pyr1]apelin-13 was the predominant isoform in cardiac tissue from patients with coronary artery disease. We tested the hypothesis that apelins have vascular and cardiac actions in human tissues in vitro and compared responses to [Pyr1]apelin-13, apelin-13, and apelin-36. In endothelium-intact mammary artery, all 3 of the apelins induced concentration-dependent vasodilatation with comparable potency (EC50: 0.6 to 1.6 nM; maximum response: 40% to 50%). Vasodilatation was abolished after endothelial removal or preincubation with indomethacin but was unaffected by preincubation with NG-nitro-l-arginine methyl ester, indicating involvement of prostanoids but not NO in dilatation by apelins in this patient group. Apelins were potent constrictors of endothelium-denuded saphenous vein (EC50: 0.6 to 1.6 nM; maximum response: 17% to 26%) and mammary artery ([Pyr1]apelin-13; EC50: 0.2 nM; maximum response: 29%). In paced atrial strips, all 3 of the peptides increased the force of contraction with subnanomolar potencies (EC50: 40 to 125 pM). For the first time, we demonstrate that the 3 principal forms of apelin have comparable potency and efficacy in human cardiovascular tissues. Apelins are potent endothelium-dependent vasodilators acting via a prostanoid-dependent mechanism; however, removal of the endothelium revealed direct vasoconstrictor actions in both the artery and vein. Furthermore, in human cardiac tissue, the apelin peptides are among the most potent endogenous positive inotropic agents yet reported.

更新日期：2009-09-01

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南