Impacts of Telomeric Length, Chronic Hypoxia, Senescence, and Senescence-Associated Secretory Phenotype on the Development of Thoracic Aortic Aneurysm
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Shortened Telomeres and Telomere Damage in Aneurysm Compared to Healthy Aorta
2.3. GLUT1 and p-eNOS Expression after Hypoxic Stress
2.4. Chronic DNA Damage and Cell Senescence in TAA Specimens
2.5. Expression of Senescence-Associated Secretory Phenotype (SASP) in Aneurysmatic Aortic Tissue
2.6. Chronic Hypoxia and Cellular Stress Correlates with the Number of Telocytes
3. Discussion
4. Materials and Methods
4.1. Patients’ Specimens
4.2. Telomere Length Measurement by PFGE/Southern Blot
4.3. Relative Telomeric Length by RT-qPCR
4.4. Telomerase Activity Assay
4.5. Immunofluorescence Staining and Microscopy
4.6. Western blot Analysis and ROS/RNS Measurements by OxySelect Assay
4.7. Antibodies
4.8. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study Population | HTA | TAV | p Value | BAV | p Value | |||||
---|---|---|---|---|---|---|---|---|---|---|
(n = 215) | (n = 41) | (n = 109) | (n = 65) | |||||||
Demographic, risk factors, and comorbidities | ||||||||||
Age (years) (range) | 60.1 | (19–81) | 54.9 | (20–79) | 62.9 | (23–81) | <0.01 | 58.3 | (19–80) | 0.12 |
female, n (%) | 73 | (33.9) | 8 | (19.5) | 51 | (46.8) | <0.05 | 14 | (21.5) | 0.50 |
Body mass index (BMI), n (range) | 27.2 | (15–45) | 25.3 | (19–30) | 26.7 | (15–45) | <0.05 | 29.0 | (18–44) | <0.01 |
Adipositas (BMI >30), n (%) | 57 | (26.5) | 2 | (4.8) | 27 | (24.8) | <0.05 | 28 | (43.1) | 0.18 |
Smoker, n (%) | 58 | (27.0) | 18 | (43.9) | 20 | (18.6) | 0.39 | 20 | (30.7) | 0.10 |
Hypertension, n (%) | 149 | (69.3) | 18 | (43.9) | 85 | (78.0) | <0.01 | 46 | (70.8) | <0.01 |
Dyslipidaemia, n (%) | 93 | (43.6) | 17 | (41.5) | 46 | (42.2) | 0.45 | 30 | (46.2) | 0.27 |
Chronic renal failure, n (%) | 31 | (14.4) | 15 | (36.6) | 11 | (10.1) | <0.01 | 5 | (7.7) | <0.01 |
Diabetes, n (%) | 25 | (11.6) | 8 | (19.5) | 9 | (8.3) | 0.18 | 8 | (12.3) | 0.05 |
COPD, n (%) | 35 | (16.3) | 3 | (7.3) | 25 | (23.0) | <0.05 | 7 | (10.8) | 0.31 |
Positive family history, n (%) | 8 | (3.7) | 1 | (2.4) | 3 | (2.8) | 0.46 | 4 | (6.2) | 0.17 |
CAD, n (%) | 68 | (31.6) | 20 | (48.8) | 32 | (29.4) | <0.05 | 16 | (24.6) | <0.05 |
CVD, n (%) | 18 | (8.4) | 7 | (17.1) | 3 | (2.8) | <0.01 | 8 | (12.3) | <0.01 |
PAD, n (%) | 19 | (8.8) | 4 | (9.8) | 7 | (6.4) | 0.26 | 8 | (12.3) | 0.18 |
Therapeutics | ||||||||||
Oral diabetes therapy, n (%) | 21 | (9.8) | 7 | (17.1) | 7 | (6.4) | 0.06 | 7 | (10.8) | 0.18 |
Statins, n (%) | 68 | (31.6) | 14 | (34.1) | 34 | (31.2) | 0.38 | 20 | (30.8) | 0.38 |
Aspirin, n (%) | 63 | (29.3) | 17 | (41.5) | 26 | (23.9) | <0.05 | 20 | (30.8) | 0.15 |
b-Blocker, n (%) | 98 | (45.6) | 20 | (48.9) | 52 | (47.8) | 0.45 | 26 | (40.0) | 0.21 |
ACE-Inhibitor, n (%) | 80 | (37.2) | 19 | (46.3) | 39 | (35.8) | 0.13 | 22 | (33.9) | 0.12 |
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Aschacher, T.; Geisler, D.; Lenz, V.; Aschacher, O.; Winkler, B.; Schaefer, A.-K.; Mitterbauer, A.; Wolf, B.; Enzmann, F.K.; Messner, B.; et al. Impacts of Telomeric Length, Chronic Hypoxia, Senescence, and Senescence-Associated Secretory Phenotype on the Development of Thoracic Aortic Aneurysm. Int. J. Mol. Sci. 2022, 23, 15498. https://doi.org/10.3390/ijms232415498
Aschacher T, Geisler D, Lenz V, Aschacher O, Winkler B, Schaefer A-K, Mitterbauer A, Wolf B, Enzmann FK, Messner B, et al. Impacts of Telomeric Length, Chronic Hypoxia, Senescence, and Senescence-Associated Secretory Phenotype on the Development of Thoracic Aortic Aneurysm. International Journal of Molecular Sciences. 2022; 23(24):15498. https://doi.org/10.3390/ijms232415498
Chicago/Turabian StyleAschacher, Thomas, Daniela Geisler, Verena Lenz, Olivia Aschacher, Bernhard Winkler, Anne-Kristin Schaefer, Andreas Mitterbauer, Brigitte Wolf, Florian K. Enzmann, Barbara Messner, and et al. 2022. "Impacts of Telomeric Length, Chronic Hypoxia, Senescence, and Senescence-Associated Secretory Phenotype on the Development of Thoracic Aortic Aneurysm" International Journal of Molecular Sciences 23, no. 24: 15498. https://doi.org/10.3390/ijms232415498