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缺氧诱导的肺动脉高压——利用自然实验

Hypoxia-induced pulmonary hypertension-Utilizing experiments of nature.

作者信息

Gassmann Max, Cowburn Andrew, Gu Hong, Li Jia, Rodriguez Marisela, Babicheva Aleksandra, Jain Pritesh P, Xiong Mingmei, Gassmann Norina N, Yuan Jason X-J, Wilkins Martin R, Zhao Lan

机构信息

Institute of Veterinary Physiology, Vetsuisse Faculty, and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.

University Peruana Cayetano Heredia (UPCH), Lima, Peru.

出版信息

Br J Pharmacol. 2021 Jan;178(1):121-131. doi: 10.1111/bph.15144. Epub 2020 Aug 28.

Abstract

An increase in pulmonary artery pressure is a common observation in adult mammals exposed to global alveolar hypoxia. It is considered a maladaptive response that places an increased workload on the right ventricle. The mechanisms initiating and maintaining the elevated pressure are of considerable interest in understanding pulmonary vascular homeostasis. There is an expectation that identifying the key molecules in the integrated vascular response to hypoxia will inform potential drug targets. One strategy is to take advantage of experiments of nature, specifically, to understand the genetic basis for the inter-individual variation in the pulmonary vascular response to acute and chronic hypoxia. To date, detailed phenotyping of highlanders has focused on haematocrit and oxygen saturation rather than cardiovascular phenotypes. This review explores what we can learn from those studies with respect to the pulmonary circulation. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc.

摘要

在成年哺乳动物暴露于全身性肺泡缺氧的情况下,肺动脉压力升高是常见现象。这被认为是一种适应性不良反应,会增加右心室的工作负荷。启动和维持压力升高的机制对于理解肺血管稳态具有重要意义。人们期望识别出对缺氧的综合血管反应中的关键分子,这将为潜在的药物靶点提供信息。一种策略是利用自然实验,具体而言,是了解个体间对急性和慢性缺氧的肺血管反应差异的遗传基础。迄今为止,对高原居民的详细表型分析主要集中在血细胞比容和血氧饱和度上,而非心血管表型。本综述探讨了我们能从这些研究中学到哪些关于肺循环的知识。相关文章:本文是关于心脏保护中的危险因素、合并症和联合用药的主题系列文章的一部分。若要查看本节中的其他文章,请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc。

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