Your browser doesn't support javascript.
loading
CNS resident macrophages enhance dysfunctional angiogenesis and circulating monocytes infiltration in brain arteriovenous malformation.
Ma, Li; Zhu, Xiaonan; Tang, Chaoliang; Pan, Peipei; Yadav, Alka; Liang, Rich; Press, Kelly; Nelson, Jeffrey; Su, Hua.
Afiliação
  • Ma L; Center for Cerebrovascular Research, University of California, San Francisco, California, USA.
  • Zhu X; Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, USA.
  • Tang C; Center for Cerebrovascular Research, University of California, San Francisco, California, USA.
  • Pan P; Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, USA.
  • Yadav A; Center for Cerebrovascular Research, University of California, San Francisco, California, USA.
  • Liang R; Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, USA.
  • Press K; Center for Cerebrovascular Research, University of California, San Francisco, California, USA.
  • Nelson J; Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, USA.
  • Su H; Center for Cerebrovascular Research, University of California, San Francisco, California, USA.
J Cereb Blood Flow Metab ; 44(6): 925-937, 2024 06.
Article em En | MEDLINE | ID: mdl-38415628
ABSTRACT
Myeloid immune cells are abundant in both ruptured and unruptured brain arteriovenous malformations (bAVMs). The role of central nervous system (CNS) resident and circulating monocyte-derived macrophages in bAVM pathogenesis has not been fully understood. We hypothesize that CNS resident macrophages enhance bAVM development and hemorrhage. RNA sequencing using cultured endothelial cells (ECs) and mouse bAVM samples revealed that downregulation of two bAVM causative genes, activin-like kinase 1 (ALK1) or endoglin, increased inflammation and innate immune signaling. To understand the role of CNS resident macrophages in bAVM development and hemorrhage, we administrated a colony-stimulating factor 1 receptor inhibitor to bAVM mice with brain focal Alk1 deletion. Transient depletion of CNS resident macrophages at an early stage of bAVM development mitigated the phenotype severity of bAVM, including a prolonged inhibition of angiogenesis, dysplastic vasculature formation, and infiltration of CNS resident and circulating monocyte-derived macrophages during bAVM development. Transient depletion of CNS resident macrophages increased EC tight junction protein expression, reduced the number of dysplasia vessels and severe hemorrhage in established bAVMs. Thus, EC AVM causative gene mutation can activate CNS resident macrophages promoting bAVM progression. CNS resident macrophage could be a therapeutic target to mitigate the development and severity of bAVMs.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Monócitos / Malformações Arteriovenosas Intracranianas / Macrófagos / Neovascularização Patológica Limite: Animals / Humans / Male Idioma: En Revista: J Cereb Blood Flow Metab Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Monócitos / Malformações Arteriovenosas Intracranianas / Macrófagos / Neovascularização Patológica Limite: Animals / Humans / Male Idioma: En Revista: J Cereb Blood Flow Metab Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos