Endothelial senescence after high-cholesterol, high-fat diet challenge in baboons.
Increasing evidence indicates that replicative senescence and premature endothelial senescence could contribute to endothelial dysfunction. This study aims at testing the hypothesis that a high-fat diet may lead to premature vascular endothelial senescence in a nonhuman primate model. We isolated endothelial cells from left and right femoral arteries in 10 baboons before and after a 7-wk high-fat dietary treatment. We compared the morphological alterations, replicative capacities, and senescence-associated beta-galactosidase activities (SA-beta-gal) at these two time points. We found that high-fat diet increased the prevalence of endothelial senescence. Endothelial replicative capacities declined dramatically, and SA-beta-gal activities increased significantly in postdietary challenge. There was no change in telomeric length using quantitative flow fluorescence in situ hybridization analysis, suggesting that some stressors lead to cell senescence independent of telomere dysfunction. Our findings that high-fat diet causes endothelial damage through the premature senescence suggest a novel mechanism for the diet-induced endothelial dysfunction.
Shi
Qiang
Q
Department of Genetics, Southwest National Primate Research Center, San Antonio, TX, USA.
Hubbard
Gene B
GB
Kushwaha
Rampratap S
RS
Rainwater
David
D
Thomas
Charles A
CA
Leland
M Michelle
MM
Vandeberg
John L
JL
Wang
Xing L
XL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005263:Femoral Artery / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010215:Papio; D016615:Telomere / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation; D001616:beta-Galactosidase / Q000378:metabolism
D002791:Cholesterol, Dietary; D001616:beta-Galactosidase