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Pathophysiology of Angiogenesis and Its Role in Vascular Disease

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Mechanisms of Vascular Disease

Abstract

Angiogenesis is the process in which new blood vessels, in particular capillaries, are formed from the pre-existing vascular network, Angiogenesis plays a critical role in normal postnatal growth and development. It is crucial in providing nourishment to granulation tissue during wound healing, as well as in the formation of collateral vessels as part of an adaptive response to vascular occlusion and ischaemia. Failure of adequate angiogenesis plays an important role in conditions including ischaemic heart disease, peripheral arterial disease (PAD), delayed wound healing and ischaemic stroke. Conversely, excessive pathological angiogenesis driven by inflammation is a key contributor to the development and progression of malignant cancers, atherosclerotic plaques, proliferative retinal disease and inflammatory arthritides, among many other pathologies. Diseases associated with angiogenesis are highly prevalent globally, with cardiovascular-related disorders and cancer being the leading causes of mortality worldwide. However, current therapies that target angiogenesis remain limited though, as anti-angiogenic agents can delay physiological angiogenic processes, causing severe side effects while pro-angiogenic therapies may cause inadvertent tumourigenesis. The intricate balance between desirable physiological angiogenesis and unwanted pathological angiogenesis involves the regulation of a suite of signalling pathways, regulatory factors and cell-to-cell interactions.

In this chapter, we outline a basic mechanistic framework by which to understand angiogenesis and summarise the key molecular factors that regulate it, particularly those that have current or potential clinical relevance. We will highlight the importance of angiogenesis in health, and in the pathophysiology of various ischaemic and inflammatory vascular diseases and describe the impact of diabetes and ageing on this process. In addition, we review the current range of therapeutic strategies designed to target angiogenesis and examine the barriers and pitfalls that have limited more successful clinical translation so far. Finally, we explore several emerging therapies that are showing great promise in pre-clinical models and offer some insights on future directions of research inquiry.

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Further Reading

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Author notes

  1. Joanne T. M. Tan and Martin K. C. Ng contributed equally to this work.

Authors and Affiliations

  1. South Australian Health and Medical Research Institute, Adelaide, SA, Australia

    Nathan K. P. Wong, Emma L. Solly, Christina A. Bursill & Joanne T. M. Tan

  2. The University of Sydney, Sydney, NSW, Australia

    Nathan K. P. Wong, Christina A. Bursill, Joanne T. M. Tan & Martin K. C. Ng

  3. The University of Adelaide, Adelaide, SA, Australia

    Emma L. Solly, Christina A. Bursill & Joanne T. M. Tan

  4. Royal Prince Alfred Hospital, Sydney, NSW, Australia

    Martin K. C. Ng

Authors
  1. Nathan K. P. Wong
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  2. Emma L. Solly
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  3. Christina A. Bursill
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  4. Joanne T. M. Tan
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  5. Martin K. C. Ng
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Correspondence to Joanne T. M. Tan .

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  1. Discipline of Surgery, The University of Adelaide, Adelaide, SA, Australia

    Robert Fitridge

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Wong, N.K.P., Solly, E.L., Bursill, C.A., Tan, J.T.M., Ng, M.K.C. (2020). Pathophysiology of Angiogenesis and Its Role in Vascular Disease. In: Fitridge, R. (eds) Mechanisms of Vascular Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-43683-4_5

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