Varani J, Dame M K, Taylor C G, Sarma V, Merino R, Kunkel R G, Nunez G, Dixit V M
Department of Pathology, University of Michigan Medical School, Ann Arbor, USA.
Lab Invest. 1995 Dec;73(6):851-8.
It has recently been shown that human umbilical vein endothelial cells (HUVEC) become increasingly sensitive to growth factor deprivation, resulting in cell death, as a function of age in culture. The overall goal of the present study was to investigate the mechanism of lethal injury in these cells and compare the injury process to other known mechanisms of injury in the same cells.
HUVEC were established in culture and maintained for four passages. Injury to first-passage cells and fourth-passage cells were examined for injury in the presence of agents that are known to confer resistance to apoptosis. Ultrastructural features of injury and DNA fragmentation patterns were assessed. Expression of factors that are known to be associated with resistance to apoptosis in other models were assessed.
Fourth-passage HUVEC undergoing injury exhibited morphologic features characteristic of apoptosis and DNA fragmentation. Agents known to inhibit apoptotic cell injury in other models inhibited injury. A20 expression was correlated with resistance to injury in fourth-passage HUVEC, but there was no correlation between bcl-2 and bcl-x expression and resistance to injury.
HUVEC injury resulting from growth factor deprivation increases as a function of age in vitro and appears to be a form of apoptosis. A20 expression may confer resistance to cell injury through this pathway.
最近研究表明，人脐静脉内皮细胞（HUVEC）随着培养年龄的增长，对生长因子剥夺变得越来越敏感，从而导致细胞死亡。本研究的总体目标是研究这些细胞中致死性损伤的机制，并将损伤过程与同一细胞中其他已知的损伤机制进行比较。
将HUVEC培养并传代四次。在已知能赋予抗凋亡能力的试剂存在的情况下，检查第一代细胞和第四代细胞的损伤情况。评估损伤的超微结构特征和DNA片段化模式。评估在其他模型中已知与抗凋亡相关的因子的表达。
经历损伤的第四代HUVEC表现出凋亡和DNA片段化的形态学特征。在其他模型中已知能抑制凋亡细胞损伤的试剂可抑制损伤。A20表达与第四代HUVEC的抗损伤能力相关，但bcl-2和bcl-x表达与抗损伤能力之间无相关性。
体外生长因子剥夺导致的HUVEC损伤随年龄增长而增加，似乎是一种凋亡形式。A20表达可能通过该途径赋予细胞抗损伤能力。
