VEGF Induces More Severe Cerebrovascular Dysplasia in Endoglin than in Alk1 Mice.

Translational Stroke Research
Qi HaoWilliam L Young

Abstract

Brain arteriovenous malformations (BAVMs) are an important cause of intracranial hemorrhage (ICH) in young adults. A small percent of BAVMs is due to hereditary hemorrhagic telangiectasia 1 and 2 (HHT1 and 2), which are caused by mutations in two genes involved in TGF-β signaling: endoglin (ENG) and activin-like kinase 1 (ALK1). The BAVM phenotype is an incomplete penetrant in HHT patients, and the mechanism is unknown. We tested the hypothesis that a "response-to-injury" triggers abnormal vascular (dysplasia) development, using Eng and Alk1 haploinsufficient mice. Adeno-associated virus (AAV) expressing vascular endothelial growth factor (VEGF) was used to mimic the injury conditions. VEGF overexpression caused a similar degree of angiogenesis in the brain of all groups, except that the cortex of Alk1(+/-) mice had a 33% higher capillary density than other groups. There were different levels of cerebrovascular dysplasia in haploinsufficient mice (Eng(+/)>Alk1(+/-)), which simulates the relative penetrance of BAVM in HHT patients (HHT1>HHT2). Few dysplastic capillaries were observed in AAV-LacZ-injected mice. Our data indicate that both angiogenic stimulation and genetic alteration are necessary for the development of dysplasia...Continue Reading

References

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Citations

Oct 1, 2013·Cellular and Molecular Life Sciences : CMLS·Deepak AtriMichael Simons
Apr 12, 2014·Translational Stroke Research·Wanqiu ChenHua Su
Jan 19, 2013·Translational Stroke Research·Shantel WeinsheimerHelen Kim
Jan 30, 2016·Cytokine & Growth Factor Reviews·Amaya García de VinuesaSabine Bailly
Feb 13, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Brian P Walcott, Randall T Peterson
Mar 26, 2011·Annals of Neurology·Espen J WalkerWilliam L Young
Feb 3, 2015·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jason E Fish, Joshua D Wythe
Sep 24, 2015·Angiogenesis·Helen ArthurWhitney Wooderchak-Donahue
Dec 10, 2015·BioMed Research International·Ming XuZhiyong Qin
Nov 18, 2014·Biochemical Society Transactions·Yi JinLars Jakobsson
Dec 30, 2014·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Jared J Y YeoDavid C Y Low
Mar 6, 2015·Frontiers in Genetics·Simon Tual-ChalotHelen M Arthur
Apr 15, 2016·Neurologia Medico-chirurgica·Masaki Komiyama
May 10, 2012·Stroke; a Journal of Cerebral Circulation·Espen J WalkerWilliam L Young
Feb 17, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Elisenda Alsina-SanchísFrancesc Viñals
Oct 1, 2017·Circulation Research·Sara I CunhaMaria Grazia Lampugnani
Jan 30, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Konstantinos GkatzisFranck Lebrin
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Mar 10, 2015·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·C R Calladine
Mar 15, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Igor GiarrettaRoberto Pola
Nov 11, 2020·Journal of Clinical Medicine·Carmelo BernabeuMichelle Letarte
Nov 25, 2020·Neural Regeneration Research·Igor Giarretta, Roberto Pola
Aug 28, 2021·International Journal of Molecular Sciences·Georgios GalarisFranck Lebrin

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