Perkett E A, Lyons R M, Moses H L, Brigham K L, Meyrick B
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
J Clin Invest. 1990 Nov;86(5):1459-64. doi: 10.1172/JCI114862.
Chronic pulmonary hypertension is associated with extensive structural remodeling of the pulmonary arterial bed. The structural changes in the arterial walls include increased production of extracellular matrix components and smooth muscle cell hypertrophy, changes that have been similarly induced by transforming growth factor-beta (TGF-beta) in culture. In the present study, experiments were performed to determine whether TGF-beta is present in sheep lung lymph, and whether TGF-beta levels were altered in an animal model of chronic pulmonary hypertension induced by continuous air embolization. Several standard biological assays for TGF-beta activity were used for these determinations including soft agar assays, inhibition of epithelial cell proliferation, and a TGF-beta-specific radioreceptor assay. In each case, control lung lymph contained high concentrations of TGF-beta (100 ng/ml) which required transient acidification for detection. Samples of lung lymph from hypertensive sheep showed a transient and early two- to threefold increase in concentrations of latent TGF-beta. This activity could be partially blocked by TGF-beta antibodies. These studies indicate that sheep lung lymph contains TGF-beta and that the level of TGF-beta increases early during the development of pulmonary hypertension. Thus, TGF-beta may contribute to the development of the structural changes in the pulmonary arteries that occur during the onset of chronic pulmonary hypertension.
慢性肺动脉高压与肺动脉床广泛的结构重塑相关。动脉壁的结构变化包括细胞外基质成分产生增加和平滑肌细胞肥大，这些变化在培养中已被转化生长因子-β（TGF-β）类似地诱导。在本研究中，进行了实验以确定TGF-β是否存在于绵羊肺淋巴中，以及在连续空气栓塞诱导的慢性肺动脉高压动物模型中TGF-β水平是否改变。使用了几种用于TGF-β活性的标准生物学测定方法进行这些测定，包括软琼脂测定、上皮细胞增殖抑制以及TGF-β特异性放射受体测定。在每种情况下，对照肺淋巴含有高浓度的TGF-β（100 ng/ml），检测需要短暂酸化。来自高血压绵羊的肺淋巴样本显示潜伏性TGF-β浓度有短暂且早期的两到三倍增加。这种活性可被TGF-β抗体部分阻断。这些研究表明绵羊肺淋巴含有TGF-β，并且在肺动脉高压发展早期TGF-β水平升高。因此，TGF-β可能促成慢性肺动脉高压发作期间肺动脉发生的结构变化的发展。
