Stenmark K R, Orton E C, Reeves J T, Voelkel N F, Crouch E C, Parks W C, Mecham R P
University of Colorado Health Sciences Center, Cardiovascular Laboratory, Denver.
Chest. 1988 Mar;93(3 Suppl):127S-133S.
We suggest that hypoxia-induced pulmonary hypertension in the newborn calf is an attractive model for studying the mechanisms underlying alterations in extracellular matrix accumulation which occur in pulmonary vascular disease. Our data support a model (Fig 7) in which the SMC, perhaps as a result of hypoxic and/or pressure-induced vessel wall injury, becomes phenotypically altered. This phenotypically altered SMC generates a factor, termed smooth muscle derived extracellular matrix factor (SMEF), and possibly other factors. SMEF, in turn, stimulates or induces elastin and collagen synthesis in fibroblasts and endothelial cells. SMEF, or an associated activity derived from phenotypically altered smooth muscle cells, also induces elastin receptor expression on the cell surface and affects the chemotactic responsiveness of vascular cells. Thus, the SMC may be able to affect both the secretory and responsive properties of cell types in the vascular wall. The SMC may be critical in the vascular remodeling in pulmonary hypertension. The possible autocrine or paracrine alteration of cellular phenotypes by smooth muscle-derived mediators provides an important new direction for future research into molecular and cellular mechanisms of connective tissue regulation in diseased vessels.
我们认为新生小牛缺氧诱导的肺动脉高压是研究肺血管疾病中细胞外基质积累改变机制的一个有吸引力的模型。我们的数据支持一种模型（图7），其中平滑肌细胞（SMC）可能由于缺氧和/或压力诱导的血管壁损伤而发生表型改变。这种表型改变的SMC产生一种因子，称为平滑肌衍生细胞外基质因子（SMEF），可能还有其他因子。反过来，SMEF刺激或诱导成纤维细胞和内皮细胞中的弹性蛋白和胶原蛋白合成。SMEF或源自表型改变的平滑肌细胞的相关活性，也诱导细胞表面的弹性蛋白受体表达，并影响血管细胞的趋化反应性。因此，SMC可能能够影响血管壁中细胞类型的分泌和反应特性。SMC在肺动脉高压的血管重塑中可能至关重要。平滑肌衍生介质对细胞表型的可能自分泌或旁分泌改变为未来研究患病血管中结缔组织调节的分子和细胞机制提供了一个重要的新方向。
