Vascular repair and regeneration as a therapeutic target for pulmonary arterial hypertension.
Vascular repair and regeneration as a therapeutic target for pulmonary arterial hypertension.
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DOI：
10.1159/000350177
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Kolb M
中科院分区：
文献类型：
--
作者：
Farkas L;Kolb M
在过去的十年中，我们对肺动脉高压（PAH）病理学的理解发生了重大变化，PAH是一种严重的毁灭性疾病，没有治愈性治疗。现在公认肺动脉内皮细胞损伤是随后发生腔闭塞性肺血管病变的中心环节。多种循环和肺驻留祖细胞和干细胞可能有助于血管完整性，并且在PAH的肺血管病变内部和附近发现了表达干细胞和祖细胞标志物的细胞存在的证据。目前可用的血管扩张剂疗法主要针对肺循环中增强的血管收缩，并有助于维持或改善右心室功能，但不能治疗肺血管重构，这是疾病的根本原因。血管基因治疗和祖细胞和干细胞细胞治疗是PAH新型治疗方案开发背景下的一个不断发展的领域。但目前大多数研究都是在动物模型中进行的临床前研究。目前的审查提供了一个概述目前的知识，基于细胞和基因治疗的方法，在PAH的血管修复和再生。
The last decade has seen substantial changes in our understanding of the pathobiology of pulmonary arterial hypertension (PAH), a severe and devastating disease without curative treatment. It is now accepted that injury to the endothelial cells of the pulmonary arteries is central for the subsequent development of lumen-obliterative lung vascular lesions. A variety of circulating and lung-resident progenitor and stem cells likely contribute to vascular integrity and evidence for the presence of cells expressing stem and progenitor cell markers is found inside of and in the immediate vicinity of the pulmonary vascular lesions in PAH. The currently available vasodilator therapies mainly target enhanced vasoconstriction in the lung circulation and help to maintain or improve right ventricular function, but do not treat pulmonary vascular remodeling, the underlying cause of the disease. Vascular gene therapy and cell therapy with progenitor and stem cells is a progressing field in the context of the development of novel treatment options for PAH. But the majority of the studies are currently performed on the level of preclinical studies in animal models. The current review provides an overview of the current knowledge on cell- and gene therapy-based approaches for vascular repair and regeneration in PAH.