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Endothelial dysfunction and angiogenesis impairment in the ageing vasculature

Nature Reviews Cardiology volume 15, pages 555–565 (2018)Cite this article

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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

  • 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.

  • 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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Fig. 1: Ageing signalling pathways that contribute to oxidative stress and endothelial dysfunction.
Fig. 2: Mechanisms by which ageing impairs angiogenesis.
Fig. 3: Ageing promotes both intrinsic angiogenic incompetence in endothelial cells and dysregulated tissue expression of genes governing angiogenesis.

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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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Nature Reviews Cardiology thanks J. Padilla and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Zoltan Ungvari, Stefano Tarantini, Tamas Kiss, Jonathan D. Wren, Cory B. Giles & Anna Csiszar

  2. Translational Geroscience Laboratory, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Zoltan Ungvari, Stefano Tarantini, Tamas Kiss & Anna Csiszar

  3. Department of Medical Physics and Informatics, Faculty of Medicine and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary

    Zoltan Ungvari, Stefano Tarantini, Tamas Kiss & Anna Csiszar

  4. Department of Pulmonology, Semmelweis University, Budapest, Hungary

    Zoltan Ungvari

  5. Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

    Jonathan D. Wren & Cory B. Giles

  6. Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

    Courtney T. Griffin

  7. J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA

    Walter Lee Murfee

  8. Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA

    Pal Pacher

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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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