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Angiogenesis, Arteriogenesis, and Mitochondrial Dysfunction

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Cardiac Remodeling

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 5))

Abstract

Angiogenesis and arteriogenesis are key processes involved in the response to occlusive arterial disease and the pathology of cancer. Angiogenesis remodels the circulatory bed by new capillary formation, while arteriogenesis remodels existing arterioles by increasing their diameter. The main molecular mechanism of angiogenesis is initiation by activation of hypoxia-inducible factor (HIF)-1, and arteriogenesis, initiated mainly by shear stress, is modulated by HIF-1 activation. Mitochondria can modulate HIF-1 activation by release of mitochondrial reactive oxygen species and alpha-ketoglutarate, a required cofactor for prolyl hydroxylation and destruction of HIF components, and thus, mitochondria can influence HIF-1-dependent angiogenesis and arteriogenesis. Mitochondria may serve as metabolic sensors that link metabolic derangements to appropriate neovascularization in health and in chronic ischemia and inappropriate neovascularization in the context of cancer. Mitochondrial remodeling or dysfunction may impair angiogenesis and contribute to the pathology of diseases, including diabetes and myocardial dysfunction. Drugs that alter mitochondrial function may alter HIF-1-dependent neovascularization and may represent novel therapies for chronic ischemic diseases and cancer.

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  1. Department of Medicine, University of Alberta, 8440 112th Street, Edmonton, AB, Canada, T6G 2B7

    M. S. McMurtry M.D., Ph.D., F.R.C.P.C.

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  1. M. S. McMurtry M.D., Ph.D., F.R.C.P.C.
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Correspondence to M. S. McMurtry M.D., Ph.D., F.R.C.P.C. .

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  1. Walter MacKenzie Health Sciences Centre, Division of Cardiology, University of Alberta, 8440-112 Street, Edmonton, T6G 2B7, Alberta, Canada

    Bodh I. Jugdutt

  2. St. Boniface General Hospital Research C, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

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McMurtry, M.S. (2013). Angiogenesis, Arteriogenesis, and Mitochondrial Dysfunction. In: Jugdutt, B., Dhalla, N. (eds) Cardiac Remodeling. Advances in Biochemistry in Health and Disease, vol 5. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5930-9_15

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