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HB-EGF depolarizes hippocampal arterioles to restore myogenic tone in a genetic model of small vessel disease.
Fontaine, Jackson T; Rosehart, Amanda C; Joutel, Anne; Dabertrand, Fabrice.
Afiliação
  • Fontaine JT; Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Rosehart AC; Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Joutel A; Department of Pharmacology, Larner College of Medicine University of Vermont, Burlington, VT, USA; Institute of Psychiatry and Neurosciences of Paris, INSERM UMR1266, University of Paris, GHU Paris Psychiatrie et Neurosciences, France.
  • Dabertrand F; Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: Fabrice.Dabertrand@CUAnschutz.edu.
Mech Ageing Dev ; 192: 111389, 2020 12.
Article em En | MEDLINE | ID: mdl-33127441
ABSTRACT
Vascular cognitive impairment, the second most common cause of dementia, profoundly affects hippocampal-dependent functions. However, while the growing literature covers complex neuronal interactions, little is known about the sustaining hippocampal microcirculation. Here we examined vasoconstriction to physiological pressures of hippocampal arterioles, a fundamental feature of small arteries, in a genetic mouse model of CADASIL, an archetypal cerebral small vessel disease. Using diameter and membrane potential recordings on isolated arterioles, we observed both blunted pressure-induced vasoconstriction and smooth muscle cell depolarization in CADASIL. This impairment was abolished in the presence of voltage-gated potassium (KV1) channel blocker 4-aminopyridine, or by application of heparin-binding EGF-like growth factor (HB-EGF), which promotes KV1 channel down-regulations. Interestingly, we observed that HB-EGF induced a depolarization of the myocyte plasma membrane within the arteriolar wall in CADASIL, but not wild-type, arterioles. Collectively, our results indicate that hippocampal arterioles in CADASIL mice display a blunted contractile response to luminal pressure, similar to the defect we previously reported in cortical arterioles and pial arteries, that is rescued by HB-EGF. Hippocampal vascular dysfunction in CADASIL could then contribute to the decreased vascular reserve associated with decreased cognitive performance, and its correction may provide a therapeutic option for treating vascular cognitive impairment.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Arteríolas / Canais de Potássio de Abertura Dependente da Tensão da Membrana / Fator de Crescimento Semelhante a EGF de Ligação à Heparina / Hipocampo Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Arteríolas / Canais de Potássio de Abertura Dependente da Tensão da Membrana / Fator de Crescimento Semelhante a EGF de Ligação à Heparina / Hipocampo Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article