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Cellular senescence in endothelial cells from atherosclerotic patients is accelerated by oxidative stress associated with cardiovascular risk factors
- Source :
- Mechanisms of Ageing and Development. 128:662-671
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
Abstract
- Risk factors for cardiovascular diseases (CVD) increase oxidative stress, and they are proposed to hasten endothelial cell (EC) damage and dysfunction. Our objective was to elucidate the impact of chronic exposure to risk factors for CVD on senescence of EC isolated and cultured from internal mammary arterial segments of patients with severe coronary artery disease. Senescence induced by serial passages resulted in progressive telomere shortening, and short initial telomeres predicted early appearance of senescence in culture. Neither time course of senescence nor telomere length was age-dependent, suggesting that biological age, rather than chronological age, determined the dynamics. Senescence appeared earlier in patients with longer history of risk factor for CVD, and multivariate analysis suggested that hypertension hastened the onset of senescence. Risk factors for CVD override the effects of chronological aging likely by generating stress-dependent damage: senescent EC exhibited oxidative stress (increase in lipid peroxydation and caveolin-1 gene expression) and cell damage markers (loss of eNOS expression and increase in Cox2 mRNA, lower TRF1 protein level). Thus, cell senescence was triggered both by telomere-dependent and -independent pathways. In conclusion, chronic exposure to risk factors for CVD accelerated the development of endothelial senescence that could contribute to the pathogenesis of CVD.
- Subjects :
- Adult
Male
Senescence
Aging
medicine.medical_specialty
Time Factors
Nitric Oxide Synthase Type III
Endothelium
Caveolin 1
Coronary Artery Disease
Biology
medicine.disease_cause
Severity of Illness Index
Body Mass Index
Pathogenesis
Risk Factors
Internal medicine
medicine
Humans
RNA, Messenger
Telomeric Repeat Binding Protein 1
Mammary Arteries
Risk factor
Cell damage
Cells, Cultured
Cellular Senescence
Aged
Cell Proliferation
Smoking
Age Factors
Endothelial Cells
Middle Aged
Telomere
medicine.disease
Endothelial stem cell
Oxidative Stress
Endocrinology
medicine.anatomical_structure
Cardiovascular Diseases
Cyclooxygenase 2
Hypertension
Cyclooxygenase 1
Female
Lipid Peroxidation
Oxidative stress
Developmental Biology
Subjects
Details
- ISSN :
- 00476374
- Volume :
- 128
- Database :
- OpenAIRE
- Journal :
- Mechanisms of Ageing and Development
- Accession number :
- edsair.doi.dedup.....7da963195959804f95cc895e5cf3b774