Your browser doesn't support javascript.
loading
Reduced mural cell coverage and impaired vessel integrity after angiogenic stimulation in the Alk1-deficient brain.
Chen, Wanqiu; Guo, Yi; Walker, Espen J; Shen, Fanxia; Jun, Kristine; Oh, S Paul; Degos, Vincent; Lawton, Michael T; Tihan, Tarik; Davalos, Dimitrios; Akassoglou, Katerina; Nelson, Jeffrey; Pile-Spellman, John; Su, Hua; Young, William L.
Afiliación
  • Chen W; Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, CA 94110, USA
Arterioscler Thromb Vasc Biol ; 33(2): 305-10, 2013 Feb.
Article en En | MEDLINE | ID: mdl-23241407
OBJECTIVE: Vessels in brain arteriovenous malformations are prone to rupture. The underlying pathogenesis is not clear. Hereditary hemorrhagic telangiectasia type 2 patients with activin receptor-like kinase 1 (Alk1) mutation have a higher incidence of brain arteriovenous malformation than the general population. We tested the hypothesis that vascular endothelial growth factor impairs vascular integrity in the Alk1-deficient brain through reduction of mural cell coverage. METHODS AND RESULTS: Adult Alk1(1f/2f) mice (loxP sites flanking exons 4-6) and wild-type mice were injected with 2×10(7) PFU adenovious-cre recombinase and 2×10(9) genome copies of adeno-associated virus-vascular endothelial growth factor to induce focal homozygous Alk1 deletion (in Alk1(1f/2f) mice) and angiogenesis. Brain vessels were analyzed 8 weeks later. Compared with wild-type mice, the Alk1-deficient brain had more fibrin (99±30×10(3) pixels/mm(2) versus 40±13×10(3); P=0.001), iron deposition (508±506 pixels/mm(2) versus 6±49; P=0.04), and Iba1(+) microglia/macrophage infiltration (888±420 Iba1(+) cells/mm(2) versus 240±104 Iba1(+); P=0.001) after vascular endothelial growth factor stimulation. In the angiogenic foci, the Alk1-deficient brain had more α-smooth muscle actin negative vessels (52±9% versus 12±7%, P<0.001), fewer vascular-associated pericytes (503±179/mm(2) versus 931±115, P<0.001), and reduced platelet-derived growth factor receptor-ß expression. CONCLUSIONS: Reduction of mural cell coverage in response to vascular endothelial growth factor stimulation is a potential mechanism for the impairment of vessel wall integrity in hereditary hemorrhagic telangiectasia type 2-associated brain arteriovenous malformation.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Telangiectasia Hemorrágica Hereditaria / Vasos Sanguíneos / Encéfalo / Pericitos / Receptores de Activinas Tipo I / Factor A de Crecimiento Endotelial Vascular / Neovascularización Patológica Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Telangiectasia Hemorrágica Hereditaria / Vasos Sanguíneos / Encéfalo / Pericitos / Receptores de Activinas Tipo I / Factor A de Crecimiento Endotelial Vascular / Neovascularización Patológica Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos