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Human arterial endothelial cells develop a mesenchymal phenotype with aging
Author(s) -
Fleenor Bradley S,
Marshall Kurt D,
Rippe Catarina,
Seals Douglas R
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.784.2
Subject(s) - mesenchymal stem cell , phenotype , vascular smooth muscle , population , smooth muscle , cell , fibroblast , endothelium , medicine , microbiology and biotechnology , in vitro , endocrinology , pathology , chemistry , biology , biochemistry , environmental health , gene
Large elastic arteries stiffen with aging and this leads to multiple cardiovascular pathologies. Arterial endothelial cells are thought to contribute to this process possibly via age‐associated reductions in nitric oxide production and consequent increases in smooth muscle cell (SMC) tone. Here we test the novel hypothesis that these cells also may contribute by changing to a mesenchymal phenotype featuring development of fibroblast/SMC‐like migratory and secretory (synthetic) properties. Human aortic endothelial cells were studied at early (27.0 ± 0.54, mean±SE), intermediate (37.0 ± 0.59) and late (45.0 ± 1.18) population doublings (PDLs), representing “young” (Y), “middle‐aged” (MA) and “old” (O) cells, respectively. Smooth muscle alpha actin (SMαA) protein expression (western blots) was greater in MA and O cells compared with Y (MA: 1.30 ± 0.05, O: 1.28 ± 0.05 vs. Y: 1.00 ± 0.05 AU; P < 0.05). Moreover, mean expression of type I collagen increased progressively with aging (Y: 1.00 ± 0.31 vs. MA: 1.40 ± 0.30 vs. O: 2.70 ± 0.43 AU; Y vs. O and MA vs. O, P < 0.05). These preliminary data are consistent with the hypothesis that replicative aging induces a vascular endothelial to mesenchymal cell transition resulting in development of a synthetic, migratory phenotype that may contribute to intimal thickening and increases in stiffness of large elastic arteries. NIH AG013038 and HL007822 , Swedish Research Council