APOPTOSIS OF HUMAN VASCULAR SMOOTH-MUSCLE CELLS DERIVED FROM NORMAL VESSELS AND CORONARY ATHEROSCLEROTIC PLAQUES
APOPTOSIS OF HUMAN VASCULAR SMOOTH-MUSCLE CELLS DERIVED FROM NORMAL VESSELS AND CORONARY ATHEROSCLEROTIC PLAQUES
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DOI：
10.1172/jci117917
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发表时间：
1995-05-01
影响因子：
15.9
通讯作者：
SCHWARTZ, SM
中科院分区：
文献类型：
--
作者：
BENNETT, MR;EVAN, GI;SCHWARTZ, SM
我们研究了人冠状动脉斑块和正常冠状动脉和主动脉来源的血管平滑肌细胞的死亡。正常动脉来源的细胞仅在去除血清生长因子后死亡。相反，斑块来源的细胞即使在高血清条件下也死亡，并且在血清去除后死亡增加。如通过延时视频显微镜、电子显微镜和DNA片段化模式所确定的，死亡的特征在于正常细胞和斑块来源的细胞中的细胞凋亡。IGF-1和PDGF被鉴定为血清中的有效存活因子，而EGF和碱性成纤维细胞生长因子几乎没有影响。6cl-2的稳定表达，6cl-2是一种调节其他细胞系中细胞凋亡的原癌基因，保护平滑肌细胞免于凋亡，尽管在来自斑块或正常血管的细胞之间内源性bcl-2表达没有可检测的差异。我们的结论是，人血管平滑肌细胞的凋亡是由特定的基因产物和当地的细胞因子作为生存因子，因此，细胞凋亡可能会调节细胞质量在正常动脉壁和较高的凋亡率看到斑块平滑肌细胞可能最终导致斑块破裂和崩溃，从而动脉粥样硬化的临床后遗症。
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 6cl-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.