Hypoxia-induced pulmonary vascular remodeling: contribution of the adventitial fibroblasts.
Hypoxia-induced pulmonary vascular remodeling: contribution of the adventitial fibroblasts.
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DOI：
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发表时间：
2000
影响因子：
2.1
通讯作者：
K. Stenmark;D. Bouchey;Raphael A. Nemenoff;Edward C. Dempsey;M. Das
中科院分区：
文献类型：
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作者：
K. Stenmark;D. Bouchey;Raphael A. Nemenoff;Edward C. Dempsey;M. Das
响应于损伤或应激的血管修复（通常称为重塑）是许多心血管异常的常见并发症，包括肺动脉高压、全身性高血压、动脉粥样硬化、静脉移植物重塑和冠状动脉球囊扩张后的再狭窄。这并不奇怪，修复和重塑经常发生在血管系统中，因为血液、血管暴露于过度的血流动力学应力，（例如高血压）、有毒血液传播因子（例如致动脉粥样硬化脂质）、局部释放的细胞因子或异常环境条件（例如缺氧），需要容易获得的机制来抵消这些不利的刺激并保护血管壁的结构和功能。据推测，这些反应是为了修复受伤的组织而进化而来的，通常会逃脱自我限制的控制，并且在血管的情况下，会导致管腔狭窄和血流阻塞。每种细胞类型（i. e.血管壁中的内皮细胞、平滑肌细胞和成纤维细胞）在对损伤的反应中起特定作用。然而，虽然内皮细胞和平滑肌细胞（SMC）在血管重塑中的作用已得到广泛研究，但对外膜成纤维细胞的关注相对较少。这可能是因为成纤维细胞是一种相对不明确的细胞，至少与SMC相比，其表现出很少的特异性细胞标志物。重要的是，已经充分证明成纤维细胞具有表达几种功能的能力，例如迁移、快速增殖、结缔组织组分的合成、响应于激活或刺激的收缩和细胞因子产生。成纤维细胞表现出的无数反应，特别是对刺激的反应，表明这些细胞在损伤修复中发挥着关键作用。这一事实已在伤口愈合的环境中得到充分证明，其中低氧环境已被证明在细胞反应中至关重要。因此，成纤维细胞可能在对缺氧和/或损伤的血管反应中发挥重要作用并不奇怪。本文就血管外膜成纤维细胞在血管应激（特别是缺氧）中的变化及其在缺氧介导的肺血管疾病中的作用作一综述。
Vascular repair in response to injury or stress (often referred to as remodeling) is a common complication of many cardiovascular abnormalities including pulmonary hypertension, systemic hypertension, atherosclerosis, vein graft remodeling and restenosis following balloon dilatation of the coronary artery. It is not surprising that repair and remodeling occurs frequently in the vasculature in that exposure of blood, vessels to either excessive hemodynamic stress (e.g. hypertension), noxious blood borne agents (e.g. atherogenic lipids), locally released cytokines, or unusual environmental conditions (e.g. hypoxia), requires readily available mechanisms to counteract these adverse stimuli and to preserve structure and function of the vessel wall. The responses, which were presumably evolutionarily developed to repair an injured tissue, often escape self-limiting control and can result, in the case of blood vessels, in lumen narrowing and obstruction to blood flow. Each cell type (i. e. endothelial cells, smooth muscle cells, and fibroblasts) in the vascular wall plays a specific role in the response to injury. However, while the roles of the endothelial cells and smooth muscle cells (SMC) in vascular remodeling have been extensively studied, relatively little attention has been given to the adventitial fibroblasts. Perhaps this is because the fibroblast is a relatively ill-defined cell which, at least compared to the SMC, exhibits few specific cellular markers. Importantly though, it has been well demonstrated that fibroblasts possess the capacity to express several functions such as migration, rapid proliferation, synthesis of connective tissue components, contraction and cytokine production in response to activation or stimulation. The myriad of responses exhibited by the fibroblasts, especially in response to stimulation, suggest that these cells could play a pivotal role in the repair of injury. This fact has been well documented in the setting of wound healing where a hypoxic environment has been demonstrated to be critical in the cellular responses. As such it is not surprising that fibroblasts may play an important role in the vascular response to hypoxia and/or injury. This paper is intended to provide a brief review of the changes that occur in the adventitial fibroblasts in response to vascular stress (especially hypoxia) and the role the activated fibroblasts might play in hypoxia-mediated pulmonary vascular disease.