title: Senescent phenotypes of skin fibroblasts from patients with Tangier disease.
abstract: 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.
authors: 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
authors: Fumihiko
authors: F
authors: Matsuura
authors: Ken-Ichi
authors: K
authors: Hirano
authors: Chiaki
authors: C
authors: Ikegami
authors: Jose C
authors: JC
authors: Sandoval
authors: Hiroyuki
authors: H
authors: Oku
authors: Miyako
authors: M
authors: Yuasa-Kawase
authors: Kazumi
authors: K
authors: Tsubakio-Yamamoto
authors: Masahiro
authors: M
authors: Koseki
authors: Daisaku
authors: D
authors: Masuda
authors: Ken-Ichi
authors: K
authors: Tsujii
authors: Masato
authors: M
authors: Ishigami
authors: Makoto
authors: M
authors: Nishida
authors: Iichiro
authors: I
authors: Shimomura
authors: Masatsugu
authors: M
authors: Hori
authors: Shizuya
authors: S
authors: Yamashita
mesh_terms: 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