Endothelial senescence after high-cholesterol, high-fat diet challenge in baboons
Abstract
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 β-galactosidase activities (SA-β-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-β-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.
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Endothelial cells are particularly sensitive to reactive oxygen species (ROS) and other DNA-damaging stressors.
“recent evidence suggests that endothelial cells are particularly sensitive to reactive oxygen species (ROS) (Nagyoszi et al. 2015; Wilhelm et al. 2017) and other DNA-damaging stressors (Shi et al. 2007; Silva et al. 2017; V oghel et al. 2007)”
From Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain (2020) · cites this paper as Shi et al. 2007
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- Authors
- Shi, Q., Hubbard, G. B., Kushwaha, R. S., Rainwater, D., Thomas, C. A., Leland, M. M., VandeBerg, J. L., & Wang, X. L.
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2007-06
- Volume
- 292
- Issue
- 6
- Pages
- H2913-H2920
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2167634473
- Cited by
- 43
- References
- 32
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 2 · 2020: 1 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 2
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- University of Texas Health Science Center at San Antonio
- National Heart, Lung, and Blood Institute (P01HL028972)
- National Cancer Institute (P30CA054174)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- endothelial cell senescence, high-fat diet, high-cholesterol diet, endothelial dysfunction, replicative senescence, senescence-associated β-galactosidase, telomere length, vascular endothelial cells, nonhuman primate model, baboons
- MeSH terms
- Animals, beta-Galactosidase, Cells, Cultured, Cholesterol, Dietary, Endothelium, Vascular, Femoral Artery, Papio, Up-Regulation, Telomere, Cellular Senescence, Apoptosis, Endothelial Cells, Cell Size, Cell Shape, Cell Proliferation, Atherosclerosis
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