Abstract
Much of the focus of research in angiogenesis has been on the molecular mechanisms regulating various critical endothelial cell processes such as migration, proliferation and capillary sprouting. This has led to a number of insights including the key roles played by VEGF signalling in initiating angiogenesis (Chung & Ferrara, 2011; Koch & Claesson‐Welsh, 2012) and Notch signalling in regulating its extent via control of these processes (Benedito & Hellstrom, 2013; Cristofaro et al, 2013; Thomas et al, 2013). This further evolved into therapeutic approaches designed to control angiogenesis by regulation of these signalling events that are now understood in a significant amount of detail. Yet little attention however has been paid so far to the metabolic cost of angiogenesis. All active cellular events, including the ones referred to above, require the expenditure of energy. The underlying assumption has always been that energy ( e.g . ATP) is abundant and is not a limiting factor as endothelial cells are typically found in the high oxygen environment of blood flow. Indeed, while arterial endothelium is bathed in blood with nearly 100 mm Hg of partial pressure of oxygen (PO2), even venous and lymphatic endothelial cells are exposed to a much higher PO2 (∼40 mmHg) than most other tissues. Furthermore, essentially all studies of growth factor signalling in vitro that have given us our current understanding of VEGF and Notch biology, have also been carried out …
Highlights
In this context, the recent study of De Bock et al (2013) is especially timely and important
ATP is generated in this fashion throughout the cell including at lamellipodia, which are crucial to capillary tip cell sprouting
The expression of the molecule itself is regulated by HIF‐1a‐ (Obach et al, 2004) and AMPK (Mendoza et al, 2012), an essential step in driving endothelial metabolism under energy‐limiting circumstances
Summary
Much of the focus of research in angiogenesis has been on the molecular mechanisms regulating various critical endothelial cell processes such as migration, proliferation and capillary sprouting This has led to a number of insights including the key roles played by VEGF signalling in initiating angiogenesis (Chung & Ferrara, 2011; Koch & Claesson‐Welsh, 2012) and Notch signalling in regulating its extent via control of these processes (Benedito & Hellstrom, 2013; Cristofaro et al, 2013; Thomas et al, 2013). The availability of energy is itself a key factor controlling sprouting: a sufficient supply of energy is enough to overcome the suppressive effect of Notch signalling that hitherto was considered to be the dominant signalling mechanism controlling this event These observations propel considerations of endothelial metabolism to the centre stage.
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