Senescent phenotypes of skin fibroblasts from patients with Tangier disease.
Tangier disease (TD) is characterized by a deficiency of high density lipoprotein (HDL) in plasma and patients with TD have an increased risk for coronary artery disease (CAD). Recently, we reported that fibroblasts from TD exhibited large and flattened morphology, which is often observed in senescent cells. On the other hand, data have accumulated to show the relationship between cellular senescence and development of atherosclerotic CAD. The aim of the present study was to investigate whether TD fibroblasts exhibited cellular senescence. The proliferation of TD fibroblasts was gradually decreased at population doubling level (PDL) approximately 10 compared with control cells. TD cells practically ceased proliferation at PDL approximately 30. DNA synthesis was markedly decreased in TD fibroblasts. TD cells exhibited a higher positive rate for senescence-associated beta-galactosidase (SA-beta-gal), which is one of the biomarkers of cellular senescence in vitro. These data showed that TD cells reached cellular senescence at an earlier PDL compared with controls. Although, there was no difference in the telomere length of fibroblasts between TD and controls at the earlier passage (PDL 6), the telomere length of TD cells was shorter than that of controls at the late passage (PDL 25). Taken together, the current study demonstrates that the late-passaged TD fibroblasts showed senescent phenotype in vitro, which might be related to the increased cardiovascular manifestations in TD patients.
Matsuura
Fumihiko
F
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. fumihiko@imed2.med.osaka-u.ac.jp
Hirano
Ken-Ichi
K
Ikegami
Chiaki
C
Sandoval
Jose C
JC
Oku
Hiroyuki
H
Yuasa-Kawase
Miyako
M
Tsubakio-Yamamoto
Kazumi
K
Koseki
Masahiro
M
Masuda
Daisaku
D
Tsujii
Ken-Ichi
K
Ishigami
Masato
M
Nishida
Makoto
M
Shimomura
Iichiro
I
Hori
Masatsugu
M
Yamashita
Shizuya
S
D000328:Adult; D002478:Cells, Cultured; D016922:Cellular Senescence; D005260:Female; D005347:Fibroblasts / Q000473:pathology* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012867:Skin / Q000473:pathology* / Q000503:physiopathology*; D013631:Tangier Disease / Q000473:pathology* / Q000503:physiopathology*; D016615:Telomere / Q000235:genetics / Q000648:ultrastructure