Vernon S M, Campos M J, Haystead T, Thompson M M, DiCorleto P E, Owens G K
Department of Medicine (Cardiology), University of Virginia School of Medicine, Charlottesville 22908, USA.
Am J Physiol. 1997 Feb;272(2 Pt 1):C582-91. doi: 10.1152/ajpcell.1997.272.2.C582.
Smooth muscle cells (SMC) within atherosclerotic lesions proliferate and exhibit phenotypic modulation, but the contribution of vascular endothelium to this process is poorly understood. Our aim was to examine the effects of endothelial cell-conditioned medium (ECCM) on vascular SMC growth and differentiation. Rat aortic ECCM stimulated a ninefold increase in [3H]thymidine incorporation and downregulated smooth muscle-specific myosin heavy chain and alpha-actin synthesis in rat aortic SMC. These effects were not inhibited by antibodies to platelet-derived growth factor (PDGF)-BB or PDGF-AB or with a PDGF beta-receptor subunit. Treatment with PDGF-BB (at a concentration found in ECCM), PDGF-AA, basic fibroblast growth factor, endothelin-1, or transforming growth factor-beta did not reproduce these effects. The ECCM activities were sensitive to heat and trypsinization, were >30 kDa in molecular mass, and bound weakly to heparin-Sepharose. Our data indicate that cultured endothelial cells produce a factor(s) that downregulates contractile protein expression in SMC, which may contribute to SMC dedifferentiation and proliferation.
动脉粥样硬化病变中的平滑肌细胞（SMC）会增殖并表现出表型调节，但血管内皮对这一过程的作用却知之甚少。我们的目的是研究内皮细胞条件培养基（ECCM）对血管SMC生长和分化的影响。大鼠主动脉ECCM刺激大鼠主动脉SMC中[3H]胸苷掺入增加了9倍，并下调了平滑肌特异性肌球蛋白重链和α-肌动蛋白的合成。这些作用不受抗血小板衍生生长因子（PDGF）-BB或PDGF-AB抗体或PDGFβ受体亚基的抑制。用PDGF-BB（在ECCM中发现的浓度）、PDGF-AA、碱性成纤维细胞生长因子、内皮素-1或转化生长因子-β处理并不能重现这些作用。ECCM的活性对热和胰蛋白酶消化敏感，分子量>30 kDa，与肝素-琼脂糖结合较弱。我们的数据表明，培养的内皮细胞产生一种或多种因子，可下调SMC中收缩蛋白的表达，这可能有助于SMC去分化和增殖。
