SMOOTH-MUSCLE MEDIATED CONNECTIVE-TISSUE REMODELING IN PULMONARY-HYPERTENSION
SMOOTH-MUSCLE MEDIATED CONNECTIVE-TISSUE REMODELING IN PULMONARY-HYPERTENSION
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DOI：
10.1126/science.3603030
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发表时间：
1987-07-24
期刊：
影响因子：
56.9
通讯作者：
VOELKEL, NF
中科院分区：
文献类型：
--
作者：
MECHAM, RP;WHITEHOUSE, LA;VOELKEL, NF
结缔组织在血管中的异常积聚有助于与疾病状态（诸如高血压和动脉粥样硬化）相关的血管生理学的改变。为了研究引起肺动脉结缔组织产生变化的细胞刺激，研究了肺泡缺氧诱导的严重肺动脉高压新生小牛血管中弹性蛋白的合成。在高血压小牛的肺动脉组织和中膜平滑肌细胞中观察到弹性蛋白的产生增加了2 - 4倍。这种弹性蛋白产生的刺激伴随着弹性蛋白信使RNA的相应增加，这与转录水平的调节一致。从高血压动物分离的肺动脉平滑肌细胞培养物中收获的条件血清含有一种或多种低分子量弹性蛋白生成因子，其刺激成纤维细胞和平滑肌细胞中弹性蛋白的产生，并改变成纤维细胞对弹性蛋白肽的趋化反应。这些结果表明，结缔组织的变化，在肺血管系统中的肺动脉高压是精心策划的中膜平滑肌细胞通过产生特定的分化因子，改变周围细胞的分泌表型和响应特性。
Abnormal accumulation of connective tissue in blood vessels contributes to alterations in vascular physiology associated with disease states such as hypertension and atherosclerosis. Elastin synthesis was studied in blood vessels from newborn calves with severe pulmonary hypertension induced by alveolar hypoxia in order to investigate the cellular stimuli that elicit changes in pulmonary arterial connective tissue production. A two- to fourfold increase in elastin production was observed in pulmonary artery tissue and medial smooth muscle cells from hypertensive calves. This stimulation of elastin production was accompanied by a corresponding increase in elastin messenger RNA consistent with regulation at the transcriptional level. Conditioned serum harvested from cultures of pulmonary artery smooth muscle cells isolated from hypertensive animals contained one or more low molecular weight elastogenic factors that stimulated the production of elastin in both fibroblasts and smooth muscle cells and altered the chemotactic responsiveness of fibroblasts to elastin peptides. These results suggest that connective tissue changes in the pulmonary vasculature in response to pulmonary hypertension are orchestrated by the medial smooth muscle cell through the generation of specific differentiation factors that alter both the secretory phenotype and responsive properties of surrounding cells.