Karyotypic and phenotypic changes during in vitro aging of human endothelial cells.
Karyotypic and phenotypic changes were found in human adult endothelial cells (EC) during aging in vitro. A trisomy of chromosome 11 was found in 11 out of 12 EC cultures examined, derived from 9 cell lines from 8 donors. The incidence of this trisomy in some cell lines increased over time from 0% to as much as 100% near the end of their in vitro life span. A number of oncogenes and other important genes are on chromosome 11. These genes might play a role in the changes observed. An increase in the percentage of polyploid cells was also found near the end of the in vitro life span in 6 lines. The cellular levels of two gene products characteristic of the EC, von Willebrand factor (vWF) or Factor VIII, and angiotensin converting enzyme (ACE) were also monitored. vWf was studied in 2 lines and was decreased in both with serial passage. ACE decreased in three out of the four lines examined. These chromosomal and phenotypic changes which occur with increasing age in vitro make the endothelial cell a suitable model to study in vitro culture-related changes, senescence, cardiovascular disease, and tumorigenesis.
Johnson
T E
TE
Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
Umbenhauer
D R
DR
Hill
R
R
Bradt
C
C
Mueller
S N
SN
Levine
E M
EM
Nichols
W W
WW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D016922:Cellular Senescence; D004730:Endothelium, Vascular / Q000166:cytology*; D005260:Female; D006801:Humans; D007621:Karyotyping; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000166:cytology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010641:Phenotype; D014841:von Willebrand Factor / Q000378:metabolism
D014841:von Willebrand Factor; D007703:Peptidyl-Dipeptidase A