Abstract
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.
Key points
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Age-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.
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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.
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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.
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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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Acknowledgements
The authors are supported by grants from the AHA (S.T.), the US National Institute on Aging (R01-AG055395, R01-AG047879, R01-AG038747, P30-AG050911, and R01AG049821), the US National Institute of Neurological Disorders and Stroke (R01-NS056218 and R01-NS100782), the US National Heart, Lung, and Blood Institute (R01-HL111178 and R01-HL134778), the Oklahoma Center for the Advancement of Science and Technology, and the Presbyterian Health Foundation. The authors acknowledge support from the National Institute on Aging-funded Geroscience Training Program in Oklahoma, USA (T32AG052363), and the EU-funded EFOP-3.6.1-16-2016-0008 programme.
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Ungvari, Z., Tarantini, S., Kiss, T. et al. Endothelial dysfunction and angiogenesis impairment in the ageing vasculature. Nat Rev Cardiol 15, 555–565 (2018). https://doi.org/10.1038/s41569-018-0030-z
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DOI: https://doi.org/10.1038/s41569-018-0030-z
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