Your browser doesn't support javascript.
loading
Epidermal Growth Factor Receptors in Vascular Endothelial Cells Contribute to Functional Hyperemia in the Brain.
Ferris, Hannah R; Stine, Nathan C; Hill-Eubanks, David C; Nelson, Mark T; Wellman, George C; Koide, Masayo.
Afiliación
  • Ferris HR; Department of Pharmacology, Larner College of Medicine University of Vermont, Burlington, VT 05405, USA.
  • Stine NC; Department of Pharmacology, Larner College of Medicine University of Vermont, Burlington, VT 05405, USA.
  • Hill-Eubanks DC; Department of Pharmacology, Larner College of Medicine University of Vermont, Burlington, VT 05405, USA.
  • Nelson MT; Department of Pharmacology, Larner College of Medicine University of Vermont, Burlington, VT 05405, USA.
  • Wellman GC; Vermont Center for Cardiovascular and Brain Health, Larner College of Medicine University of Vermont, Burlington, VT 05405, USA.
  • Koide M; Division of Cardiovascular Sciences, University of Manchester, Manchester M13 9PL, UK.
Int J Mol Sci ; 24(22)2023 Nov 14.
Article en En | MEDLINE | ID: mdl-38003472
Functional hyperemia-activity-dependent increases in local blood perfusion-underlies the on-demand delivery of blood to regions of enhanced neuronal activity, a process that is crucial for brain health. Importantly, functional hyperemia deficits have been linked to multiple dementia risk factors, including aging, chronic hypertension, and cerebral small vessel disease (cSVD). We previously reported crippled functional hyperemia in a mouse model of genetic cSVD that was likely caused by depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) in capillary endothelial cells (EC) downstream of impaired epidermal growth factor receptor (EGFR) signaling. Here, using EC-specific EGFR-knockout (KO) mice, we directly examined the role of endothelial EGFR signaling in functional hyperemia, assessed by measuring increases in cerebral blood flow in response to contralateral whisker stimulation using laser Doppler flowmetry. Molecular characterizations showed that EGFR expression was dramatically decreased in freshly isolated capillaries from EC-EGFR-KO mice, as expected. Notably, whisker stimulation-induced functional hyperemia was significantly impaired in these mice, an effect that was rescued by administration of PIP2, but not by the EGFR ligand, HB-EGF. These data suggest that the deletion of the EGFR specifically in ECs attenuates functional hyperemia, likely via depleting PIP2 and subsequently incapacitating Kir2.1 channel functionality in capillary ECs. Thus, our study underscores the role of endothelial EGFR signaling in functional hyperemia of the brain.
Asunto(s)
Palabras clave
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: Células Endoteliales / Hiperemia Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
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: Células Endoteliales / Hiperemia Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza