Adventitial fibroblasts: defining a role in vessel wall remodeling.
Adventitial fibroblasts: defining a role in vessel wall remodeling.
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DOI：
10.1165/ajrcmb.22.1.f172
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发表时间：
2000
影响因子：
6.4
通讯作者：
Bradley H. Strauss;Marlene Rabinovitch
中科院分区：
文献类型：
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作者：
Bradley H. Strauss;Marlene Rabinovitch
在动脉壁病理学中，我们传统上将注意力集中在内侧肥厚和新内膜病变的发展上。这些病变是肺动脉高压和球囊血管成形术后再狭窄、动脉粥样硬化和移植动脉病的一个特征。内膜增生的病理特征是平滑肌细胞 (SMC) 增殖和迁移到正在发育的新内膜，以及细胞外基质 (ECM) 蛋白（包括胶原蛋白、弹性蛋白和蛋白聚糖）的合成和分泌 (1-4)。研究人员还暗示了第二个过程，称为血管重塑，是指响应血流动力学变化或各种形式的血管损伤而发生的整个血管结构的改变。在肺动脉高压中，该术语用于描述特别是缺氧时发生的内侧和外膜增厚。在全身动脉壁病理生理学中，重塑的定义略有不同，用于描述血管整体尺寸的变化，无论是扩大还是收缩（5-9）。在这种情况下，重塑可以是适应性反应，导致整体管腔直径增加（正重塑），也可以是适应不良反应，导致整体管腔尺寸更小（负重塑）。最近对动脉重塑的认识表明，外膜层通过与中膜和内膜的相互作用，成为重塑的重要调节器。在肺动脉高压中，外膜增厚、细胞结构增加和 ECM 沉积在小肌性肺动脉中最为突出 (10, 11)，其通常具有许多与全身肌性动脉相同的结构特征。这包括血管供应，即血管滋养管，它为外膜和中膜外部提供营养，并且还充当循环炎症细胞的进入部位，受刺激后从外膜和中膜的外血管层向内膜迁移 (12)。外膜通常也充满成纤维细胞，成纤维细胞似乎在动脉修复中发挥重要作用。多种血管壁损伤导致外膜和中膜发生显着的结构变化。这些包括成纤维细胞向肌成纤维细胞的转变、肌成纤维细胞增殖、肌成纤维细胞凋亡、肌成纤维细胞迁移至内膜、外膜纤维化和基质金属蛋白酶（MMP）的表达。评估这些活动在肺和体循环重塑发病机制中的证据非常重要。尽管肺循环和体循环肌动脉中的外膜成纤维细胞有许多共同特性，但也存在需要进一步阐明的差异，特别是在对缺氧的反应方面。
In arterial wall pathology, we have traditionally focused our attention on the development of medial hypertrophy and the neointimal lesion. These lesions are a feature of pulmonary hypertension and restenosis after balloon angioplasty, atherosclerosis, and transplant arteriopathy. Intimal hyperplasia is characterized pathologically by smoothmuscle cell (SMC) proliferation and migration into the developing neointima, and synthesis and secretion of extracellular matrix (ECM) proteins, including collagen, elastin, and proteoglycans (1–4). Investigators have also implicated a second process termed vascular remodeling to refer to alterations in the entire vessel architecture that occur in response to hemodynamic changes or various forms of vascular injury. In pulmonary hypertension, this term has been used to describe the medial and adventitial thickening that occurs particularly in response to hypoxia. In systemic arterial wall pathophysiology, a somewhat different definition of remodeling has been used to describe changes in overall vessel dimensions, either enlargement or constriction (5–9). In this context, remodeling can be either an adaptive response, resulting in increased overall luminal diameter (positive remodeling) or a maladaptive response, resulting in a smaller overall lumen size (negative remodeling). Recent insights into arterial remodeling have implicated the adventitial layer as an important modulator of remodeling through its interactions with the media and intima. In pulmonary hypertension, adventitial thickening with increased cellularity and ECM deposition are most prominent in the small, muscular pulmonary arteries (10, 11), which typically share a number of structural features in common with systemic muscular arteries. This includes a vascular supply, the vasa vasorum, which provides nutrients to the adventitia and the outer part of the media, and which also acts as an entry site for circulating inflammatory cells stimulated to migrate from the outer vessel layers of the adventitia and media toward the intima (12). The adventitia is also normally populated by fibroblasts, which seem to play a significant role in arterial repair.A wide variety of vessel wall injuries contribute to significant structural changes in both the adventitia and media. These include transition of fibroblasts to myofibroblasts, myofibroblast proliferation, myofibroblast apoptosis, myofibroblast migration into the intima, adventitial fibrosis, and expression of matrix metalloproteinases (MMPs). It is important to assess evidence for these activities in the pathogenesis of remodeling in the pulmonary and systemic circulation. Although many properties are shared between adventitial fibroblasts in the muscular arteries of the pulmonary and systemic circulation, differences also exist that need further elucidation, particularly in the response to hypoxia.