Pericytes in Hereditary Hemorrhagic Telangiectasia

Galaris, Georgios; Thalgott, Jérémy H.; Lebrin, Franck P. G.

doi:10.1007/978-3-030-16908-4_10

Georgios Galaris⁷,
Jérémy H. Thalgott⁷ &
Franck P. G. Lebrin^7,8,9

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1147))

1821 Accesses
6 Citations
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Abstract

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized by multi-systemic vascular dysplasia affecting 1 in 5000 people worldwide. Individuals with HHT suffer from many complications including nose and gastrointestinal bleeding, anemia, iron deficiency, stroke, abscess, and high-output heart failure. Identification of the causative gene mutations and the generation of animal models have revealed that decreased transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) signaling and increased vascular endothelial growth factor (VEGF) signaling activity in endothelial cells are responsible for the development of the vascular malformations in HHT. Perturbations in these key pathways are thought to lead to endothelial cell activation resulting in mural cell disengagement from the endothelium. This initial instability state causes the blood vessels to response inadequately when they are exposed to angiogenic triggers resulting in excessive blood vessel growth and the formation of vascular abnormalities that are prone to bleeding. Drugs promoting blood vessel stability have been reported as effective in preclinical models and in clinical trials indicating possible interventional targets based on a normalization approach for treating HHT. Here, we will review how disturbed TGF-β and VEGF signaling relates to blood vessel destabilization and HHT development and will discuss therapeutic opportunities based on the concept of vessel normalization to treat HHT.

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Department of Internal Medicine (Nephrology), Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
Georgios Galaris, Jérémy H. Thalgott & Franck P. G. Lebrin
Physics for Medicine, ESPCI, INSERM U1273, CNRS, Paris, France
Franck P. G. Lebrin
MEMOLIFE Laboratory of Excellence and PSL Research University, Paris, France
Franck P. G. Lebrin

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Georgios Galaris
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Jérémy H. Thalgott
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Franck P. G. Lebrin
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Correspondence to Franck P. G. Lebrin .

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Department of Radiology, Columbia University Medical Center, New York, NY, USA
Alexander Birbrair

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Galaris, G., Thalgott, J.H., Lebrin, F.P.G. (2019). Pericytes in Hereditary Hemorrhagic Telangiectasia. In: Birbrair, A. (eds) Pericyte Biology in Disease. Advances in Experimental Medicine and Biology, vol 1147. Springer, Cham. https://doi.org/10.1007/978-3-030-16908-4_10

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DOI: https://doi.org/10.1007/978-3-030-16908-4_10
Published: 31 May 2019
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-16907-7
Online ISBN: 978-3-030-16908-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)

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