Suppr超能文献

缺氧和综合应激反应促进肺动脉高压和子痫前期:药物研发的意义。

Hypoxia and the integrated stress response promote pulmonary hypertension and preeclampsia: Implications in drug development.

机构信息

Lawrence D. Longo MD Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.

出版信息

Drug Discov Today. 2021 Nov;26(11):2754-2773. doi: 10.1016/j.drudis.2021.07.011. Epub 2021 Jul 22.

Abstract

Chronic hypoxia is a common cause of pulmonary hypertension, preeclampsia, and intrauterine growth restriction (IUGR). The molecular mechanisms underlying these diseases are not completely understood. Chronic hypoxia may induce the generation of reactive oxygen species (ROS) in mitochondria, promote endoplasmic reticulum (ER) stress, and result in the integrated stress response (ISR) in the pulmonary artery and uteroplacental tissues. Numerous studies have implicated hypoxia-inducible factors (HIFs), oxidative stress, and ER stress/unfolded protein response (UPR) in the development of pulmonary hypertension, preeclampsia and IUGR. This review highlights the roles of HIFs, mitochondria-derived ROS and UPR, as well as their interplay, in the pathogenesis of pulmonary hypertension and preeclampsia, and their implications in drug development.

摘要

慢性缺氧是肺动脉高压、先兆子痫和宫内生长受限(IUGR)的常见原因。这些疾病的分子机制尚不完全清楚。慢性缺氧可能在肺血管和胎盘组织中诱导线粒体中活性氧(ROS)的产生,促进内质网(ER)应激,并导致综合应激反应(ISR)。许多研究表明,缺氧诱导因子(HIFs)、氧化应激和 ER 应激/未折叠蛋白反应(UPR)在肺动脉高压、先兆子痫和 IUGR 的发生发展中起作用。本综述强调了 HIFs、线粒体衍生的 ROS 和 UPR 及其相互作用在肺动脉高压和先兆子痫发病机制中的作用,以及它们在药物开发中的意义。

相似文献

1
Hypoxia and the integrated stress response promote pulmonary hypertension and preeclampsia: Implications in drug development.
Drug Discov Today. 2021 Nov;26(11):2754-2773. doi: 10.1016/j.drudis.2021.07.011. Epub 2021 Jul 22.
5
Pathophysiology of placental-derived fetal growth restriction.
Am J Obstet Gynecol. 2018 Feb;218(2S):S745-S761. doi: 10.1016/j.ajog.2017.11.577.
6
Adaptations of the human placenta to hypoxia: opportunities for interventions in fetal growth restriction.
Hum Reprod Update. 2021 Apr 21;27(3):531-569. doi: 10.1093/humupd/dmaa053.
7
Fetal chronic hypoxia and oxidative stress in diabetic pregnancy. Could fetal erythropoietin improve offspring outcomes?
Free Radic Biol Med. 2019 Oct;142:32-37. doi: 10.1016/j.freeradbiomed.2019.03.012. Epub 2019 Mar 18.
8
The interaction of ER stress and autophagy in trophoblasts: navigating pregnancy outcome†.
Biol Reprod. 2024 Aug 15;111(2):292-311. doi: 10.1093/biolre/ioae066.
10
NFAT5 Is Up-Regulated by Hypoxia: Possible Implications in Preeclampsia and Intrauterine Growth Restriction.
Biol Reprod. 2015 Jul;93(1):14. doi: 10.1095/biolreprod.114.124644. Epub 2015 May 20.

引用本文的文献

1
Multiple analytical perspectives of mitochondrial genes in the context of preeclampsia: potential diagnostic markers.
Front Immunol. 2025 Jul 17;16:1595706. doi: 10.3389/fimmu.2025.1595706. eCollection 2025.
3
MicroRNA-210 Mediates Hypoxic Pulmonary Hypertension in the Newborn Lamb.
Hypertension. 2025 Jun;82(6):1151-1163. doi: 10.1161/HYPERTENSIONAHA.124.23061. Epub 2025 Apr 23.
6
Metabolic theory of preeclampsia: implications for maternal cardiovascular health.
Am J Physiol Heart Circ Physiol. 2024 Sep 1;327(3):H582-H597. doi: 10.1152/ajpheart.00170.2024. Epub 2024 Jul 5.
7
Hypoxia-induced pulmonary hypertension in adults and newborns: implications for drug development.
Drug Discov Today. 2024 Jun;29(6):104015. doi: 10.1016/j.drudis.2024.104015. Epub 2024 May 6.
9
Modulation of NRF2/KEAP1 Signaling in Preeclampsia.
Cells. 2023 Jun 4;12(11):1545. doi: 10.3390/cells12111545.

本文引用的文献

1
Hypoxia and Mitochondrial Dysfunction in Pregnancy Complications.
Antioxidants (Basel). 2021 Mar 8;10(3):405. doi: 10.3390/antiox10030405.
2
PERK inhibition attenuates vascular remodeling in pulmonary arterial hypertension caused by mutation.
Sci Signal. 2021 Jan 26;14(667):eabb3616. doi: 10.1126/scisignal.abb3616.
3
The Role of Mitochondrial Dysfunction in Preeclampsia: Causative Factor or Collateral Damage?
Am J Hypertens. 2021 May 22;34(5):442-452. doi: 10.1093/ajh/hpab003.
4
Translatable mitochondria-targeted protection against programmed cardiovascular dysfunction.
Sci Adv. 2020 Aug 19;6(34):eabb1929. doi: 10.1126/sciadv.abb1929. eCollection 2020 Aug.
7
The integrated stress response: From mechanism to disease.
Science. 2020 Apr 24;368(6489). doi: 10.1126/science.aat5314.
8
HIF‑1α affects trophoblastic apoptosis involved in the onset of preeclampsia by regulating FOXO3a under hypoxic conditions.
Mol Med Rep. 2020 Jun;21(6):2484-2492. doi: 10.3892/mmr.2020.11050. Epub 2020 Apr 1.
10
Cellular adaptation to hypoxia through hypoxia inducible factors and beyond.
Nat Rev Mol Cell Biol. 2020 May;21(5):268-283. doi: 10.1038/s41580-020-0227-y. Epub 2020 Mar 6.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验