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Endothelial dysfunction and angiogenesis impairment in the ageing vasculature
Open accessAbstract
Ageing is the main risk factor for the development of cardiovascular diseases. A central mechanism by which ageing promotes vascular pathologies is compromising endothelial health. The age-related attenuation of endothelium-dependent dilator responses (endothelial dysfunction) associated with impairment of angiogenic processes and the subsequent pathological remodelling of the microcirculation contribute to compromised tissue perfusion and exacerbate functional decline in older individuals. This Review focuses on cellular, molecular, and functional changes that occur in the endothelium during ageing. We explore the links between oxidative and nitrative stress and the conserved molecular pathways affecting endothelial dysfunction and impaired angiogenesis during ageing. We also speculate on how these pathological processes could be therapeutically targeted. An improved understanding of endothelial biology in older patients is crucial for all cardiologists because maintenance of a competently functioning endothelium is critical for adequate tissue perfusion and long-term cardiac health.Cellular, molecular, and functional changes occur in the endothelium during ageing. Ungvari and colleagues explore the links between oxidative and nitrative stress and the conserved molecular pathways affecting endothelial dysfunction and impaired angiogenesis during ageing, and also speculate on how these pathological processes might be therapeutically targeted.Key pointsAge-related endothelial dysfunction associated with impairment of angiogenic processes and the subsequent pathological remodelling of the microcirculation contribute to compromised tissue perfusion and exacerbate functional decline in older individuals.The mechanisms underlying age-related endothelial dysfunction are multifaceted and are likely to involve increased oxidative and nitrative stress and alterations in the conserved molecular pathways affecting common ageing processes.Age-related impairment of angiogenesis probably results from reduced nitric oxide bioavailability, metabolic dysregulation, altered angiomiR expression, NRF2 dysfunction, endothelial senescence and apoptosis, alterations in anti-geronic circulating factors and inducers of angiogenesis, and impaired pericyte function.Anti-ageing interventions that prevent or reverse age-related endothelial dysfunction and improve angiogenesis are expected to confer cardiovascular protection and delay functional decline in older individuals, extending health span.
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Metadata
- Authors
- Ungvari, Z., Tarantini, S., Kiss, T., Wren, J. D., Giles, C. B., Griffin, C. T., Murfee, W. L., Pacher, P., & Csiszar, A.
- Venue
- Nature Reviews Cardiology
- Published
- 2018-05-24
- Volume
- 15
- Issue
- 9
- Pages
- 555-565
- ISSN
- 1759-5002 (ISSN-L)
- 1759-5010
- OpenAlex
- W2803815839
- Cited by
- 473
- References
- 21
- FWCI
- 5.09
- Type
- journal article
- Language
- en
- Open access
- green
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