Woods M, Bishop-Bailey D, Pepper J R, Evans T W, Mitchell J A, Warner T D
William Harvey Research Institute, London, England.
J Cardiovasc Pharmacol. 1998;31 Suppl 1:S348-50. doi: 10.1097/00005344-199800001-00097.
Many pathologic conditions are associated with elevations in the production of endothelin-1 (ET-1) in the blood vessel wall. Because many of these conditions are cytokine-driven we examined the effects of a mixture of cytokines and lipopolysaccharide on ET-1 production in human vascular smooth-muscle (VSMC) cells derived from the internal mammary artery (IMA) and saphenous vein (SV). Incubation of VSMCs from IMA and SV with a combination of tumor necrosis factor-alpha (10 ng/ml), interferon-gamma (1,000 U/ml), interleukin-1 beta (500 U/ml) and lipopolysaccharide (10 micrograms/ml) for up to 48 h markedly elevated the expression of mRNA for ET-1 and the release of ET-1 into the culture medium. We conclude that low levels of ET-1 mRNA and peptide production in human VSMCs are markedly increased by exposure to cytokines and LPS. This suggests that during inflammatory states the VSMC, as well as the endothelium, may be a site of significant ET-1 production in the blood vessel wall.
许多病理状况都与血管壁中内皮素 -1（ET-1）生成增加有关。由于这些状况中有许多是由细胞因子驱动的，我们研究了细胞因子和脂多糖混合物对源自乳内动脉（IMA）和大隐静脉（SV）的人血管平滑肌（VSMC）细胞中ET-1生成的影响。将来自IMA和SV的VSMC与肿瘤坏死因子 -α（10 ng/ml）、干扰素 -γ（1000 U/ml）、白细胞介素 -1β（500 U/ml）和脂多糖（10微克/ml）的组合孵育长达48小时，显著提高了ET-1的mRNA表达以及ET-1释放到培养基中的量。我们得出结论，暴露于细胞因子和脂多糖会使人类VSMC中低水平的ET-1 mRNA和肽生成显著增加。这表明在炎症状态下，VSMC以及内皮细胞可能是血管壁中ET-1大量生成的部位。
