Bennett M R, Evan G I, Schwartz S M
Department of Pathology, University of Washington, Seattle 98195, USA.
J Clin Invest. 1995 May;95(5):2266-74. doi: 10.1172/JCI117917.
We studied death of human vascular smooth muscle cells derived from coronary plaques and normal coronary arteries and aorta. Cells from normal arteries underwent death only upon removal of serum growth factors. In contrast, plaque-derived cells died even in high serum conditions, and death increased after serum withdrawal. Death was characteristically by apoptosis in both normal and plaque-derived cells, as determined by time-lapse videomicroscopy, electron microscopy, and DNA fragmentation patterns. IGF-1 and PDGF were identified as potent survival factors in serum, whereas EGF and basic fibroblast growth factor had little effect. Stable expression of bcl-2, a protooncogene that regulates apoptosis in other cell lines, protected smooth muscle cells from apoptosis, although there was no detectable difference in endogenous bcl-2 expression between cells from plaques or normal vessels. We conclude that apoptosis of human vascular smooth muscle cells is regulated by both specific gene products and local cytokines acting as survival factors. Apoptosis may therefore regulate cell mass in the normal arterial wall and the higher rates of apoptosis seen in plaque smooth muscle cells may ultimately contribute to plaque rupture and breakdown and thus to the clinical sequelae of atherosclerosis.
我们研究了源自冠状动脉斑块以及正常冠状动脉和主动脉的人血管平滑肌细胞的死亡情况。来自正常动脉的细胞仅在去除血清生长因子后才会死亡。相比之下，源自斑块的细胞即使在高血清条件下也会死亡，并且在血清撤出后死亡增加。通过延时视频显微镜、电子显微镜和DNA片段化模式确定，正常细胞和源自斑块的细胞的死亡特征均为凋亡。胰岛素样生长因子-1（IGF-1）和血小板衍生生长因子（PDGF）被确定为血清中的有效存活因子，而表皮生长因子（EGF）和碱性成纤维细胞生长因子作用甚微。原癌基因bcl-2在其他细胞系中调节凋亡，其稳定表达可保护平滑肌细胞免于凋亡，尽管来自斑块或正常血管的细胞之间内源性bcl-2表达没有可检测到的差异。我们得出结论，人血管平滑肌细胞的凋亡受特定基因产物和作为存活因子的局部细胞因子的共同调节。因此，凋亡可能调节正常动脉壁中的细胞数量，并且在斑块平滑肌细胞中观察到的较高凋亡率可能最终导致斑块破裂和崩解，从而导致动脉粥样硬化的临床后果。
