Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PL006

Keynote Lecture

Therapeutic potential of vascular growth factors

K. Alitalo1

1. Wihuri Research Institute and Center of Excellence in Translational Cancer Biology, University of Helsinki, Helsinki, Finland.

Antiangiogenic therapy has been a success in the treatment of age-related macular degeneration, but most cancer patients are either refractory or acquire resistance to anti-angiogenic therapeutics. A combination of angiogenesis inhibitors based on knowledge of the major interacting angiogenesis signaling pathways could be used to advance the efficacy of tumor therapy. - Impaired angiogenesis has been implicated in adipose tissue dysfunction and the development of obesity and associated metabolic disorders. New experimental findings indicate that vascular endothelial growth factors can activate the thermogenic program in adipose tissue and even increase the basal metabolic rate, thus preventing diet-induced obesity and related metabolic complications. Several attempts have been made to stimulate angiogenesis and arteriogenesis in tissue ischemia, with limited success. One of the obstacles has been the property of angiogenic growth factors to promote vascular leakage, leading to tissue edema and fibrin deposition, which however can be counteracted by angiopoietins. This could lead to control of vascular leakage in sepsis and other critically ill patients. However, so far, growth factors suitable for angiogenic therapy have not yet provided significant help for patients with cardiovascular disease, but here, better understanding of the biology of the vascular growth factors may facilitate therapeutics development. The growth of lymphatic vessels, lymphangiogenesis, is involved in a number of pathological processes including tissue inflammation and tumor dissemination, but is insufficient in patients suffering from lymphedema, a debilitating condition characterized by chronic tissue edema and impaired immunity. A lymphangiogenic growth factor is currently moving to phase 2 clinical trial in human lymphedema. The recent discovery of meningeal lymphatic vessels may extend the therapeutic potential of lymphangiogenic growth factors and their inhibitors to neurodegenerative and neuroinflammatory diseases.

Where applicable, experiments conform with Society ethical requirements