Cardiac Mesenchymal Stem Cells Promote Fibrosis and Remodeling in Heart Failure: Role of PDGF Signaling.
Cardiac Mesenchymal Stem Cells Promote Fibrosis and Remodeling in Heart Failure: Role of PDGF Signaling.
复制标题
心脏间充质干细胞促进心力衰竭的纤维化和重塑：PDGF信号转导的作用。
DOI：
10.1016/j.jacbts.2022.01.004
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发表时间：
2022-05
影响因子：
9.7
通讯作者：
Prabhu, Sumanth D.
中科院分区：
文献类型：
--
作者：
Hamid, Tariq;Xu, Yuanyuan;Ismahil, Mohamed Ameen;Rokosh, Gregg;Jinno, Miki;Zhou, Guihua;Wang, Qiongxin;Prabhu, Sumanth D.
关键词：
驻留的 cMSC 包含一个独特的间充质群体，该群体会暂时扩张，并在衰竭的心脏中表现出促纤维化和促炎症的特征。衰竭心脏中的 cMSC 经历表型转换，其特征是促炎症和促纤维化反应增强。促炎性巨噬细胞促进来自衰竭心脏的 cMSC 的肌成纤维细胞分化命运，部分是由 PDGF/PDGF 受体 β 激活介导的。在心肌梗塞小鼠模型中，药理学 PDGF 受体抑制可减轻长期心脏重塑、炎症、肥大和纤维化，并增加心肌毛细血管密度。抑制病理性 cMSC 表型，或恢复正常 cMSC 表型，可能会对抗心肌梗死后心脏纤维化和衰竭的进展。心力衰竭（HF）的特点是进行性纤维化。成纤维细胞和间充质干细胞（MSC）都可以分化为促纤维化肌成纤维细胞。 MSC 分泌并表达血小板源性生长因子（PDGF）及其受体。我们假设心脏间充质干细胞 (cMSC) 中的 PDGF 信号传导促进其肌成纤维细胞分化，并加剧心肌梗死后左心室重塑和纤维化。我们发现来自心肌梗塞后衰竭心脏的 cMSC 表现出改变的表型。体外抑制 PDGF 信号传导可抑制 cMSC-肌成纤维细胞分化，而在已形成的缺血性心力衰竭期间的体内抑制可减轻左心室重塑和功能，并减少心肌纤维化、肥大和炎症。因此，调节 cMSC PDGF 受体表达可能代表一种限制心力衰竭病理性心脏纤维化的新方法。
Resident cMSCs comprise a distinct mesenchymal population that is temporally expanded and exhibit pro-fibrotic and pro-inflammatory features in failing hearts. cMSCs in failing hearts undergo a phenotypic switch characterized by enhanced pro-inflammatory and pro-fibrotic responses. Pro-inflammatory macrophages promote a myofibroblast differentiation fate of cMSCs from failing hearts, in part mediated by PDGF/PDGF receptor β activation. Pharmacologic PDGF receptor inhibition in a mouse model of myocardial infarction alleviated long-term cardiac remodeling, inflammation, hypertrophy, and fibrosis and increased myocardial capillary density. Inhibiting the pathologic cMSC phenotype, or restoring a normal cMSC phenotype, may combat the progression of cardiac fibrosis and failure after myocardial infarction. Heart failure (HF) is characterized by progressive fibrosis. Both fibroblasts and mesenchymal stem cells (MSCs) can differentiate into pro-fibrotic myofibroblasts. MSCs secrete and express platelet-derived growth factor (PDGF) and its receptors. We hypothesized that PDGF signaling in cardiac MSCs (cMSCs) promotes their myofibroblast differentiation and aggravates post–myocardial infarction left ventricular remodeling and fibrosis. We show that cMSCs from failing hearts post–myocardial infarction exhibit an altered phenotype. Inhibition of PDGF signaling in vitro inhibited cMSC–myofibroblast differentiation, whereas in vivo inhibition during established ischemic HF alleviated left ventricular remodeling and function, and decreased myocardial fibrosis, hypertrophy, and inflammation. Modulating cMSC PDGF receptor expression may thus represent a novel approach to limit pathologic cardiac fibrosis in HF.
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DOI：
10.1186/1755-1536-5-15
发表时间：
2012-09-03
期刊：
Fibrogenesis & tissue repair
影响因子：
--
作者：
Fan D;Takawale A;Lee J;Kassiri Z
通讯作者：
Kassiri Z
影响因子：
4.8
作者：
Gazdic, Marina;Volarevic, Vladislav;Stojkovic, Miodrag
通讯作者：
Stojkovic, Miodrag
影响因子：
2.7
作者：
Estabragh, Zahra Raisi;Knight, Katy;Clark, Richard E.
通讯作者：
Clark, Richard E.
影响因子：
37.8
作者：
CONRAD, CH;BROOKS, WW;BING, OHL
通讯作者：
BING, OHL
影响因子：
4.3
作者：
Farahani RM;Xaymardan M
通讯作者：
Xaymardan M