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Impacts of Telomeric Length, Chronic Hypoxia, Senescence, and Senescence-Associated Secretory Phenotype on the Development of Thoracic Aortic Aneurysm
- Source :
- International Journal of Molecular Sciences; Volume 23; Issue 24; Pages: 15498
- Publication Year :
- 2022
-
Abstract
- Thoracic aortic aneurysm (TAA) is an age-related and life-threatening vascular disease. Telomere shortening is a predictor of age-related diseases, and its progression is associated with premature vascular disease. The aim of the present work was to investigate the impacts of chronic hypoxia and telomeric DNA damage on cellular homeostasis and vascular degeneration of TAA. We analyzed healthy and aortic aneurysm specimens (215 samples) for telomere length (TL), chronic DNA damage, and resulting changes in cellular homeostasis, focusing on senescence and apoptosis. Compared with healthy thoracic aorta (HTA), patients with tricuspid aortic valve (TAV) showed telomere shortening with increasing TAA size, in contrast to genetically predisposed bicuspid aortic valve (BAV). In addition, TL was associated with chronic hypoxia and telomeric DNA damage and with the induction of senescence-associated secretory phenotype (SASP). TAA-TAV specimens showed a significant difference in SASP-marker expression of IL-6, NF-κB, mTOR, and cell-cycle regulators (γH2AX, Rb, p53, p21), compared to HTA and TAA-BAV. Furthermore, we observed an increase in CD163+ macrophages and a correlation between hypoxic DNA damage and the number of aortic telocytes. We conclude that chronic hypoxia is associated with telomeric DNA damage and the induction of SASP in a diseased aortic wall, promising a new therapeutic target.
- Subjects :
- telomere
aneurysm
DNA damage
senescence-associated secretory phenotype
cell death
thoracic aorta
telocytes
Aortic Aneurysm, Thoracic
Organic Chemistry
Heart Valve Diseases
General Medicine
Catalysis
Computer Science Applications
Inorganic Chemistry
Bicuspid Aortic Valve Disease
Aortic Valve
Humans
Senescence-Associated Secretory Phenotype
Physical and Theoretical Chemistry
Molecular Biology
Spectroscopy
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 23
- Issue :
- 24
- Database :
- OpenAIRE
- Journal :
- International journal of molecular sciences
- Accession number :
- edsair.doi.dedup.....7b640f941cded89a558f3d24e8f7a2b9