高级检索
中华结核和呼吸杂志
期刊首页
过刊列表
高级检索
稿件发表
• 综述 •
ENGLISH ABSTRACT
代谢重编程在肺动脉高压中的研究进展
张若旸
刘杰
孙英
王炜
王辰
作者及单位信息
·
DOI： 10.3760/cma.j.cn112147-20210820-00578
Metabolic reprogramming in pulmonary hypertension
Zhang Ruoyang
Liu Jie
Sun Ying
Wang Wei
Wang Chen
Authors Info & Affiliations
Zhang Ruoyang
Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
Liu Jie
Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
Sun Ying
Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
Wang Wei
Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
Wang Chen
Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
·
DOI： 10.3760/cma.j.cn112147-20210820-00578
1295
286
0
0
4
2
PDF下载
APP内阅读
摘要

肺动脉高压是指由多种临床原因引起的肺动脉压力异常升高的病理生理状态，然而其发病机制还不完全清楚。肺血管结构细胞（平滑肌细胞、内皮细胞及成纤维细胞等）和免疫细胞（巨噬细胞等）中发生的代谢重编程被认为是肺动脉高压发病过程中的重要机制，后者介导了肺血管重塑并导致肺动脉高压。已有许多研究发现了肺动脉高压中复杂的代谢重编程现象，并基于代谢通路靶点进行药物干预。本文将对代谢重编程在肺动脉高压中的作用研究进行综述。

ABSTRACT

Pulmonary hypertension is a pathophysiological disorder with elevated pulmonary artery pressures that may involve multiple clinical conditions, yet the mechanism of pulmonary hypertension remains unclear. Metabolic reprogramming of structural cells (smooth muscle cells, endothelial cells, fibroblasts etc.) and immune cells (macrophages etc.) is a hallmark of pulmonary hypertension and leads to pulmonary vascular remodeling. Many studies have investigated the metabolic reprogramming in pulmonary hypertension and some potential therapeutic targets have been developed. In this review, recent work on metabolic programming in pulmonary hypertension is summarized.

Wang Wei, Email: nc.defudabe.umccnibor_yw
Copyright by Chinese Medical Association
No content published by the journals of Chinese Medical Association may be reproduced or abridged without authorization. Please do not use or copy the layout and design of the journals without permission.
All articles published represent the opinions of the authors, and do not reflect the official policy of the Chinese Medical Association or the Editorial Board, unless this is clearly specified.
引用本文

张若旸,刘杰,孙英,等. 代谢重编程在肺动脉高压中的研究进展[J]. 中华结核和呼吸杂志,2022,45(03)：313-317.

DOI:10.3760/cma.j.cn112147-20210820-00578

PERMISSIONS

Request permissions for this article from CCC.

评价本文
*以上评分为匿名评价

版权归中华医学会所有。

未经授权，不得转载、摘编本刊文章，不得使用本刊的版式设计。

除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。

肺动脉高压是由多种临床情况引起的肺动脉压力异常升高的血流动力学状态。肺动脉压力的异常升高导致右心负荷增大，造成右心功能不全，从而引起一系列临床表现。临床上，根据病因和发病机制将肺动脉高压分为五类 ［ 1 ］ ，即，动脉性肺动脉高压（pulmonary arterial hypertension，PAH），如特发性肺动脉高压、遗传性肺动脉高压等；左心疾病相关性肺动脉高压（pulmonary hypertension due to left heart disease），如由于心脏瓣膜病导致的肺动脉压力被动性升高；肺部疾病和（或）低氧相关性肺动脉高压（hypoxia pulmonary hypertension，HPH），如继发于慢性阻塞性肺疾病、间质性肺疾病等的肺动脉高压；慢性血栓栓塞性肺动脉高压（chronic thromboembolic pulmonary hypertension，CTEPH）；多种未明机制所致肺动脉高压（pulmonary hypertension with unclear and/or multifactorial mechanisms），如骨髓增生异常、结节病等导致的肺动脉高压。
肺动脉高压严重影响患者生活质量和寿命，虽然近年来随着马西替坦（Macitentan）、利奥西呱（Riociguat）等药物逐渐进入临床，该病的治疗效果得到一定程度的改善 ［ 2 , 3 ］ ，但总体预后仍较差，严重危害患者生命健康和社会公共卫生情况。因此，针对肺动脉高压发病机制的研究仍需深入开展。
代谢重编程最早在肿瘤中被发现和研究，通常用于表示在高度增殖的肿瘤细胞中发生的代谢途径和代谢产物改变，这些代谢改变往往能够适应和支撑肿瘤的生长和增殖需求 ［ 4 ］ 。随着研究进展，代谢重编程已在各种细胞中被广泛研究。目前已有越来越多的证据表明，与肺循环有关的结构细胞（成纤维细胞、内皮细胞、平滑肌细胞等）和免疫细胞（T细胞、巨噬细胞等）中的糖、脂质和氨基酸代谢紊乱与肺血管和右心室的结构改变存在深刻广泛的联系。因此，代谢重编程的具体机制及新型药物靶点研发已成为肺动脉高压重要研究方向之一 ［ 5 , 6 , 7 ］ ，并已在动物和细胞水平的研究中发现了一些有潜力的干预靶点。本文将从不同代谢途径角度对肺动脉高压代谢重编程的研究进行综述。
试读结束，您可以通过登录机构账户或个人账户后获取全文阅读权限。
参考文献
[1]
Simonneau G , Montani D , Celermajer DS ,et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension[J]. Eur Respir J, 2019,53(1)DOI: 10.1183/13993003.01913-2018 .
返回引文位置Google Scholar
百度学术
万方数据
[2]
Ghofrani HA , Humbert M , Langleben D ,et al. Riociguat: Mode of Action and Clinical Development in Pulmonary Hypertension[J]. Chest, 2017,151(2):468-480. DOI: 10.1016/j.chest.2016.05.024 .
返回引文位置Google Scholar
百度学术
万方数据
[3]
Mehta S , Sastry B , Souza R ,et al. Macitentan Improves Health-Related Quality of Life for Patients With Pulmonary Arterial Hypertension: Results From the Randomized Controlled SERAPHIN Trial[J]. Chest, 2017,151(1):106-118. DOI: 10.1016/j.chest.2016.08.1473 .
返回引文位置Google Scholar
百度学术
万方数据
[4]
Faubert B , Solmonson A , DeBerardinis RJ . Metabolic reprogramming and cancer progression[J]. Science, 2020,368(6487). DOI: 10.1126/science.aaw5473 .
返回引文位置Google Scholar
百度学术
万方数据
[5]
Suliman HB , Nozik-Grayck E . Mitochondrial Dysfunction: Metabolic Drivers of Pulmonary Hypertension[J]. Antioxid Redox Signal, 2019,31(12):843-857. DOI: 10.1089/ars.2018.7705 .
返回引文位置Google Scholar
百度学术
万方数据
[6]
Barnes J , Dweik RA . Is pulmonary hypertension a metabolic disease?[J]. Am J Respir Crit Care Med , 2014,190(9):973-975. DOI: 10.1164/rccm.201409-1702ED .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Rubin LJ . Metabolic dysfunction in the pathogenesis of pulmonary hypertension[J]. Cell Metab, 2010,12(4):313-314. DOI: 10.1016/j.cmet.2010.09.006 .
返回引文位置Google Scholar
百度学术
万方数据
[8]
Liberti MV , Locasale JW . The Warburg Effect: How Does it Benefit Cancer Cells?[J]. Trends Biochem Sci, 2016,41(3):211-218. DOI: 10.1016/j.tibs.2015.12.001 .
返回引文位置Google Scholar
百度学术
万方数据
[9]
Marsboom G , Wietholt C , Haney CR ,et al. Lung ¹⁸ F-fluorodeoxyglucose positron emission tomography for diagnosis and monitoring of pulmonary arterial hypertension [J]. Am J Respir Crit Care Med, 2012,185(6):670-679. DOI: 10.1164/rccm.201108-1562OC .
返回引文位置Google Scholar
百度学术
万方数据
[10]
Zhao L , Ashek A , Wang L ,et al. Heterogeneity in lung (18)FDG uptake in pulmonary arterial hypertension: potential of dynamic (18)FDG positron emission tomography with kinetic analysis as a bridging biomarker for pulmonary vascular remodeling targeted treatments[J]. Circulation, 2013,128(11):1214-1224. DOI: 10.1161/CIRCULATIONAHA.113.004136 .
返回引文位置Google Scholar
百度学术
万方数据
[11]
Xu W , Koeck T , Lara AR ,et al. Alterations of cellular bioenergetics in pulmonary artery endothelial cells[J]. Proc Natl Acad Sci U S A, 2007,104(4):1342-1347. DOI: 10.1073/pnas.0605080104 .
返回引文位置Google Scholar
百度学术
万方数据
[12]
Smolders VF , Zodda E , Quax P ,et al. Metabolic Alterations in Cardiopulmonary Vascular Dysfunction[J]. Front Mol Biosci, 2018,5:120. DOI: 10.3389/fmolb.2018.00120 .
返回引文位置Google Scholar
百度学术
万方数据
[13]
D′Alessandro A , El Kasmi KC , Plecitá-Hlavatá L ,et al. Hallmarks of Pulmonary Hypertension: Mesenchyma l and Inflammatory Cell Metabolic Reprogramming [J]. Antioxid Redox Signal, 2018,28(3):230-250. DOI: 10.1089/ars.2017.7217 .
返回引文位置Google Scholar
百度学术
万方数据
[14]
Yao C , Yu J , Taylor L ,et al. Protein Expression by Human Pulmonary Artery Smooth Muscle Cells Containing a BMPR2 Mutation and the Action of ET-1 as Determined by Proteomic Mass Spectrometry[J]. Int J Mass Spectrom, 2015,378:347-359. DOI: 10.1016/j.ijms.2014.10.006 .
返回引文位置Google Scholar
百度学术
万方数据
[15]
Chettimada S , Gupte R , Rawat D ,et al. Hypoxia-induced glucose-6-phosphate dehydrogenase overexpression and-activation in pulmonary artery smooth muscle cells: implication in pulmonary hypertension[J]. Am J Physiol Lun g Cell Mol Physiol , 2015,308(3):L287-300. DOI: 10.1152/ajplung.00229.2014 .
返回引文位置Google Scholar
百度学术
万方数据
[16]
Li M , Riddle S , Zhang H ,et al. Metabolic Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Corepressor C-Terminal Binding Protein-1[J]. Circulation, 2016,134(15):1105-1121. DOI: 10.1161/CIRCULATIONAHA.116.023171 .
返回引文位置Google Scholar
百度学术
万方数据
[17]
El Kasmi KC , Pugliese SC , Riddle SR ,et al. Adventitial fibroblasts induce a distinct proinflammatory/profibrotic macrophage phenotype in pulmonary hypertension[J]. J Immunol, 2014,193(2):597-609. DOI: 10.4049/jimmunol.1303048 .
返回引文位置Google Scholar
百度学术
万方数据
[18]
Li M , Riddle S , Kumar S ,et al. Microenvironmental Regulation of Macrophage Transcriptomic and Metabolomic Profiles in Pulmonary Hypertension[J]. Front Immunol, 2021,12:640718. DOI: 10.3389/fimmu.2021.640718 .
返回引文位置Google Scholar
百度学术
万方数据
[19]
Tinajero MG , Gotlieb AI . Recent Developments in Vascular Adventitial Pathobiology: The Dynamic Adventitia as a Complex Regulator of Vascular Disease[J]. Am J Pathol, 2020,190(3):520-534. DOI: 10.1016/j.ajpath.2019.10.021 .
返回引文位置Google Scholar
百度学术
万方数据
[20]
Kovacs L , Cao Y , Han W ,et al. PFKFB3 in Smooth Muscle Promotes Vascular Remodeling in Pulmonary Arterial Hypertension[J]. Am J Respir Crit Care Med, 2019,200(5):617-627. DOI: 10.1164/rccm.201812-2290OC .
返回引文位置Google Scholar
百度学术
万方数据
[21]
Cao Y , Zhang X , Wang L ,et al. PFKFB3-mediated endothelial glycolysis promotes pulmonary hypertension[J]. Proc Natl Acad Sci U S A, 2019,116(27):13394-13403. DOI: 10.1073/pnas.1821401116 .
返回引文位置Google Scholar
百度学术
万方数据
[22]
Caruso P , Dunmore BJ , Schlosser K ,et al. Identification of MicroRNA-124 as a Major Regulator of Enhanced Endothelial Cell Glycolysis in Pulmonary Arterial Hypertension via PTBP1 (Polypyrimidine Tract Binding Protein) and Pyruvate Kinase M2[J]. Circulation, 2017,136(25):2451-2467. DOI: 10.1161/CIRCULATIONAHA.117.028034 .
返回引文位置Google Scholar
百度学术
万方数据
[23]
Zhang H , Wang D , Li M ,et al. Metabolic and Proliferative State of Vascular Adventitial Fibroblasts in Pulmonary Hypertension Is Regulated Through a MicroRNA-124/PTBP1 (Polypyrimidine Tract Binding Protein 1)/Pyruvate Kinase Muscle Axis[J]. Circulation, 2017,136(25):2468-2485. DOI: 10.1161/CIRCULATIONAHA.117.028069 .
返回引文位置Google Scholar
百度学术
万方数据
[24]
Thenappan T , Ormiston ML , Ryan JJ ,et al. Pulmonary arterial hypertension: pathogenesis and clinical management[J]. BMJ, 2018,360:j5492. DOI: 10.1136/bmj.j5492 .
返回引文位置Google Scholar
百度学术
万方数据
[25]
Fessel JP , Hamid R , Wittmann BM ,et al. Metabolomic analysis of bone morphogenetic protein receptor type 2 mutations in human pulmonary endothelium reveals widespread metabolic reprogramming[J]. Pulm Circ, 2012,2(2):201-213. DOI: 10.4103/2045-8932.97606 .
返回引文位置Google Scholar
百度学术
万方数据
[26]
Oldham WM , Clish CB , Yang Y ,et al. Hypoxia-Mediated Increases in L-2-hydroxyglutarate Coordinate the Metabolic Response to Reductive Stress[J]. Cell Metab, 2015,22(2):291-303. DOI: 10.1016/j.cmet.2015.06.021 .
返回引文位置Google Scholar
百度学术
万方数据
[27]
Sakao S , Daimon M , Voelkel NF ,et al. Right ventricular sugars and fats in chronic thromboembolic pulmonary hypertension[J]. Int J Cardiol, 2016,219:143-149. DOI: 10.1016/j.ijcard.2016.06.010 .
返回引文位置Google Scholar
百度学术
万方数据
[28]
Graham BB , Kumar R , Mickael C ,et al. Severe pulmonary hypertension is associated with altered right ventricle metabolic substrate uptake[J]. Am J Physiol Lung Cell Mol Physiol, 2015,309(5):L435-440. DOI: 10.1152/ajplung.00169.2015 .
返回引文位置Google Scholar
百度学术
万方数据
[29]
Tian L , Wu D , Dasgupta A ,et al. Epigenetic Metabolic Reprogramming of Right Ventricular Fibroblasts in Pulmonary Arterial Hypertension: A Pyruvate Dehydrogenase Kinase-Dependent Shift in Mitochondrial Metabolism Promotes Right Ventricular Fibrosis[J]. Circ Res, 2020,126(12):1723-1745. DOI: 10.1161/CIRCRESAHA.120.316443 .
返回引文位置Google Scholar
百度学术
万方数据
[30]
Rawat DK , Alzoubi A , Gupte R ,et al. Increased reactive oxygen species, metabolic maladaptation, and autophagy contribute to pulmonary arterial hypertension-induced ventricular hypertrophy and diastolic heart failure[J]. Hypertension, 2014,64(6):1266-1274. DOI: 10.1161/HYPERTENSIONAHA.114.03261 .
返回引文位置Google Scholar
百度学术
万方数据
[31]
Varghese MV , Niihori M , Eccles CA ,et al. Antioxidant-Conjugated Peptide Attenuated Metabolic Reprogramming in Pulmonary Hypertension[J]. Antioxidants (Basel), 2020,9(2). DOI: 10.3390/antiox9020104 .
返回引文位置Google Scholar
百度学术
万方数据
[32]
Smolders V , Rodríguez C , Morén C ,et al. Decreased Glycolysis as Metabolic Fingerprint of Endothelial Cells in Chronic Thromboembolic Pulmonary Hypertension[J]. Am J Respir Cell Mol Biol, 2020,63(5):710-713. DOI: 10.1165/rcmb.2019-0409LE .
返回引文位置Google Scholar
百度学术
万方数据
[33]
Ohira H , deKemp R , Pena E ,et al. Shifts in myocardial fatty acid and glucose metabolism in pulmonary arterial hypertension: a potential mechanism for a maladaptive right ventricular response[J]. Eur Heart J Cardiovasc Imaging, 2016,17(12):1424-1431. DOI: 10.1093/ehjci/jev136 .
返回引文位置Google Scholar
百度学术
万方数据
[34]
Brittain EL , Talati M , Fessel JP ,et al. Fatty Acid Metabolic Defects and Right Ventricular Lipotoxicity in Human Pulmonary Arterial Hypertension[J]. Circulation, 2016,133(20):1936-1944. DOI: 10.1161/CIRCULATIONAHA.115.019351 .
返回引文位置Google Scholar
百度学术
万方数据
[35]
Tang Y , Li G . Chronic exposure to high fatty acids impedes receptor agonist-induced nitric oxide production and increments of cytosolic Ca2+levels in endothelial cells[J]. J Mol Endocrinol, 2011,47(3):315-326. DOI: 10.1530/JME-11-0082 .
返回引文位置Google Scholar
百度学术
万方数据
[36]
Semen K , Yelisyeyeva O , Jarocka-Karpowicz I ,et al. Sildenafil reduces signs of oxidative stress in pulmonary arterial hypertension: Evaluation by fatty acid composition, level of hydroxynonenal and heart rate variability[J]. Redox Biol, 2016,7:48-57. DOI: 10.1016/j.redox.2015.11.009 .
返回引文位置Google Scholar
百度学术
万方数据
[37]
Luo L , Wu J , Lin T ,et al. Influence of atorvastatin on metabolic pattern of rats with pulmonary hypertension[J]. Aging (Albany NY), 2021,13(8):11954-11968. DOI: 10.18632/aging.202898 .
返回引文位置Google Scholar
百度学术
万方数据
[38]
Zhuang W , Lian G , Huang B ,et al. CPT1 regulates the proliferation of pulmonary artery smooth muscle cells through the AMPK-p53-p21 pathway in pulmonary arterial hypertension[J]. Mol Cell Biochem, 2019,455(1-2):169-183. DOI: 10.1007/s11010-018-3480-z .
返回引文位置Google Scholar
百度学术
万方数据
[39]
Hou C , Chen J , Zhao Y ,et al. The Emerging Role of Fatty Acid Synthase in Hypoxia-Induced Pulmonary Hypertensive Mouse Energy Metabolism[J]. Oxid Med Cell Longev, 2021,2021:9990794. DOI: 10.1155/2021/9990794 .
返回引文位置Google Scholar
百度学术
万方数据
[40]
Singh N , Manhas A , Kaur G ,et al. Inhibition of fatty acid synthase is protective in pulmonary hypertension[J]. Br J Pharmacol, 2016,173(12):2030-2045. DOI: 10.1111/bph.13495 .
返回引文位置Google Scholar
百度学术
万方数据
[41]
Mprah R , Adzika GK , Gyasi YI ,et al. Glutaminolysis: A Driver of Vascular and Cardiac Remodeling in Pulmonary Arterial Hypertension[J]. Front Cardiovasc Med, 2021,8:667446. DOI: 10.3389/fcvm.2021.667446 .
返回引文位置Google Scholar
百度学术
万方数据
[42]
Egnatchik RA , Brittain EL , Shah AT ,et al. Dysfunctional BMPR2 signaling drives an abnormal endothelial requirement for glutamine in pulmonary arterial hypertension[J]. Pulm Circ, 2017,7(1):186-199. DOI: 10.1086/690236 .
返回引文位置Google Scholar
百度学术
万方数据
[43]
Piao L , Fang YH , Parikh K ,et al. Cardiac glutaminolysis: a maladaptive cancer metabolism pathway in the right ventricle in pulmonary hypertension[J]. J Mol Med (Berl), 2013,91(10):1185-1197. DOI: 10.1007/s00109-013-1064-7 .
返回引文位置Google Scholar
百度学术
万方数据
[44]
Dieffenbach PB , Haeger CM , Coronata A ,et al. Arterial stiffness induces remodeling phenotypes in pulmonary artery smooth muscle cells via YAP/TAZ-mediated repression of cyclooxygenase-2[J]. Am J Physiol Lung Cell Mol Physiol, 2017,313(3):L628-628L647. DOI: 10.1152/ajplung.00173.2017 .
返回引文位置Google Scholar
百度学术
万方数据
[45]
Zheng HK , Zhao JH , Yan Y ,et al. Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline[J]. Respir Res, 2018,19(1):94. DOI: 10.1186/s12931-018-0800-5 .
返回引文位置Google Scholar
百度学术
万方数据
[46]
Swietlik EM , Ghataorhe P , Zalewska KI ,et al. Plasma metabolomics exhibit response to therapy in chronic thromboembolic pulmonary hypertension[J]. Eur Respir J, 2021,57(4). DOI: 10.1183/13993003.03201-2020 .
返回引文位置Google Scholar
百度学术
万方数据
[47]
Michelakis ED , Gurtu V , Webster L ,et al. Inhibition of pyruvate dehydrogenase kinase improves pulmonary arterial hypertension in genetically susceptible patients[J]. Sci Transl Med, 2017,9(413). DOI: 10.1126/scitranslmed.aao4583 .
返回引文位置Google Scholar
百度学术
万方数据
备注信息
A
王炜，Email： nc.defudabe.umccnibor_yw
B

张若旸, 刘杰, 孙英, 等. 代谢重编程在肺动脉高压中的研究进展[J]. 中华结核和呼吸杂志, 2022, 45(3): 313-317. DOI: 10.3760/cma.j.cn112147-20210820-00578.

C
所有作者声明无利益冲突
D
国家自然科学基金 (81770049)
首都医科大学科研培育基金 (PYZ19065)
评论 （0条）
注册
登录
时间排序
暂无评论，发表第一条评论抢沙发
最新推荐
更多
人工智能在肺动脉高压辅助诊断中的应用进展
陈纪元 等
中华医学杂志 2023,103(02)
巨噬细胞代谢重编程在肺动脉高压发病机制及治疗中作用的研究进展
康世威 等
实用心脑肺血管病杂志 2022,30(03)
中国肺动脉高压诊断与治疗指南（2021版）
中华医学会呼吸病学分会肺栓塞与肺血管病学组 等
中华医学杂志 2021,101(01)
代谢重编程与近端肾小管损伤的研究进展
李佳颖 等
中华肾脏病杂志 2020,36(11)
MedAI助手（体验版）
文档即答
智问智答
机器翻译
回答内容由人工智能生成，我社无法保证其准确性和完整性，该生成内容不代表我们的态度或观点，仅供参考。
生成快照
文献快照

你好，我可以帮助您更好的了解本文，请向我提问您关注的问题。

0/2000

《中华医学会杂志社用户协议》 | 《隐私政策》

《SparkDesk 用户协议》 | 《SparkDesk 隐私政策》

网信算备340104764864601230055号 | 网信算备340104726288401230013号

技术支持：

历史对话
本文全部
还没有聊天记录
设置
模式
纯净模式沉浸模式
字号
小中大