Your browser doesn't support javascript.
loading
Chronic cerebral hypoxia promotes arteriogenic remodeling events that can be identified by reduced endoglin (CD105) expression and a switch in ß1 integrins.
Boroujerdi, Amin; Welser-Alves, Jennifer V; Tigges, Ulrich; Milner, Richard.
Afiliación
  • Boroujerdi A; Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
J Cereb Blood Flow Metab ; 32(9): 1820-30, 2012 Sep.
Article en En | MEDLINE | ID: mdl-22739620
Chronic cerebral hypoxia leads to a strong vascular remodeling response, though little is known about which part of the vascular tree is modified, or whether this response includes formation of new arterial vessels. In this study, we examined this process in detail, analyzing how hypoxia (8% O(2) for 14 days) alters the size distribution of vessels, number of arteries/arterioles, and expression pattern of endoglin (CD105), a marker of angiogenic endothelial cells in tumors. We found that cerebral hypoxia promoted the biggest increase in the number of medium to large size vessels, and this correlated with increased numbers of alpha smooth muscle actin (α-SMA)-positive arterial vessels. Surprisingly, hypoxia induced a marked reduction in CD105 expression on brain endothelial cells (BECs) within remodeling arterial vessels, and these BECs also displayed an angiogenic switch in ß1 integrins (from α6 to α5), previously described for developmental angiogenesis. In vitro, transforming growth factor (TGF)-ß1 also promoted this switch of BEC ß1 integrins. Together, these results show that cerebral hypoxia promotes arteriogenesis, and identify reduced CD105 expression as a novel marker of arteriogenesis. Furthermore, our data suggest a mechanistic model whereby BECs in remodeling arterial vessels downregulate CD105 expression, which alters TGF-ß1 signaling, to promote a switch in ß1 integrins and arteriogenic remodeling.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hipoxia Encefálica / Arterias Cerebrales / Neovascularización Fisiológica / Integrina beta1 / Péptidos y Proteínas de Señalización Intracelular Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Cereb Blood Flow Metab Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hipoxia Encefálica / Arterias Cerebrales / Neovascularización Fisiológica / Integrina beta1 / Péptidos y Proteínas de Señalización Intracelular Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Cereb Blood Flow Metab Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos