Endothelial cell clonality, heterogeneity and dysfunction in pulmonary arterial hypertension.
Endothelial cell clonality, heterogeneity and dysfunction in pulmonary arterial hypertension.
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DOI：
10.3389/fmed.2023.1304766
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发表时间：
2023
影响因子：
3.9
通讯作者：
Farkas, Laszlo
中科院分区：
文献类型：
--
作者：
Newcomb, Geoffrey;Farkas, Laszlo
近年来，我们对肺动脉高压（PAH）病理生理学的认识不断发展，内皮细胞（EC）功能障碍和炎症在该疾病的发展中起着不可或缺的作用。肺血管内的内皮细胞在维持血管完整性和屏障功能、调节气体交换和促进血管张力方面发挥着独特的作用。利用单细胞转录组学，研究表明存在多个独特的EC亚群，具有不同的表型。在对损伤或某些应激源（如缺氧）的反应中，可能存在异常内皮损伤修复的失调反应，涉及其他肺血管细胞甚至免疫细胞。这种异常的信号级联可能是PAH患者肺动脉重构的主要驱动因素。最近的研究已经研究了EC克隆扩增、免疫失调和基因突变在PAH发病机制中的作用。本文综述了有关EC亚群的现有文献，以及EC发生异常生理表型和导致多环芳烃的复杂机制。我们的目标是提供一个框架，以了解独特的肺EC生物学和病理生理参与多环芳烃的发展。
Our understanding of the pathophysiology of pulmonary arterial hypertension (PAH) has evolved over recent years, with the recognition that endothelial cell (EC) dysfunction and inflammation play an integral role in the development of this disease. ECs within the pulmonary vasculature play a unique role in maintaining vascular integrity and barrier function, regulating gas exchange, and contributing to vascular tone. Using single-cell transcriptomics, research has shown that there are multiple, unique EC subpopulations with different phenotypes. In response to injury or certain stressors such as hypoxia, there can be a dysregulated response with aberrant endothelial injury repair involving other pulmonary vascular cells and even immune cells. This aberrant signaling cascade is potentially a primary driver of pulmonary arterial remodeling in PAH. Recent studies have examined the role of EC clonal expansion, immune dysregulation, and genetic mutations in the pathogenesis of PAH. This review summarizes the existing literature on EC subpopulations and the intricate mechanisms through which ECs develop aberrant physiologic phenotypes and contribute to PAH. Our goal is to provide a framework for understanding the unique pulmonary EC biology and pathophysiology that is involved in the development of PAH.
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影响因子：
64.8
作者：
Gillich A;Zhang F;Farmer CG;Travaglini KJ;Tan SY;Gu M;Zhou B;Feinstein JA;Krasnow MA;Metzger RJ
通讯作者：
Metzger RJ
影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.
影响因子：
16.6
作者：
Gräf S;Haimel M;Bleda M;Hadinnapola C;Southgate L;Li W;Hodgson J;Liu B;Salmon RM;Southwood M;Machado RD;Martin JM;Treacy CM;Yates K;Daugherty LC;Shamardina O;Whitehorn D;Holden S;Aldred M;Bogaard HJ;Church C;Coghlan G;Condliffe R;Corris PA;Danesino C;Eyries M;Gall H;Ghio S;Ghofrani HA;Gibbs JSR;Girerd B;Houweling AC;Howard L;Humbert M;Kiely DG;Kovacs G;MacKenzie Ross RV;Moledina S;Montani D;Newnham M;Olschewski A;Olschewski H;Peacock AJ;Pepke-Zaba J;Prokopenko I;Rhodes CJ;Scelsi L;Seeger W;Soubrier F;Stein DF;Suntharalingam J;Swietlik EM;Toshner MR;van Heel DA;Vonk Noordegraaf A;Waisfisz Q;Wharton J;Wort SJ;Ouwehand WH;Soranzo N;Lawrie A;Upton PD;Wilkins MR;Trembath RC;Morrell NW
通讯作者：
Morrell NW
影响因子：
15.9
作者：
Hickey, Michele M.;Lam, Jennifer C.;Simon, M. Celeste
通讯作者：
Simon, M. Celeste
DOI：
10.1164/rccm.201709-1835oc
发表时间：
2018-09-15
影响因子：
24.7
作者：
Dai, Zhiyu;Zhu, Maggie M.;Zhao, You-Yang
通讯作者：
Zhao, You-Yang