Reduced angiogenic responses in adult endoglin heterozygous mice
Authors:
- Alicia Rodríguez-BarberoARAlicia Rodríguez-Barbero
- Marta PrietoMPMarta Prieto
- Mourad ToporsianMourad Toporsian
- Miguel PericachoMiguel Pericacho
- Juan V Rivas-ElenaJRJuan V Rivas-Elena
- Juana ObreoJOJuana Obreo
- Angela WangAWAngela Wang
- Fernando Pérez-BarriocanalFPFernando Pérez-Barriocanal
- Miguel ArévaloMAMiguel Arévalo
- Carmelo BernabéuCarmelo Bernabéu
- Michelle LetarteMLMichelle Letarte
- 1 March 2006
- journal article
- Published by Oxford University Press (OUP) in Cardiovascular Research
- Vol. 69 (4) , 845-854
Abstract
To determine if angiogenesis is altered in adult Endoglin heterozygous (Eng(+/-)) mice, the animal model for the vascular disorder hereditary hemorrhagic telangiectasia type 1 (HHT1). Primary cultures of endothelial cells were generated from Eng(+/-) and Eng(+/+) mice and analyzed for proliferation, migration, and ability to form capillary-like tubes. Endothelial cells derived from umbilical veins of newborns (HUVEC) with an HHT1 genotype were also tested for capillary formation. Two in vivo models of angiogenesis were tested in the Eng(+/-) and Eng(+/+) mice: Matrigel implant-dependent angiogenesis and reperfusion following hindlimb ischemia. The Eng(+/-) endothelial cells displayed significantly reduced proliferation and migration, increased collagen production, and decreased NO synthase expression and vascular endothelial growth factor (VEGF) secretion. They also showed impaired capillary tube formation in vitro, as did the HHT1 HUVEC. These endothelial cell-specific abnormalities were associated with impaired Matrigel-dependent capillary tube formation in vivo and delayed reperfusion following hindlimb ischemia. Although vascular development is normal in Eng(+/-) mice, angiogenic abnormalities were observed in the adult mice and their isolated endothelial cells. These results suggest that a normal level of endoglin is required for full angiogenic activity.Keywords
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