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2016 ; 126
(12
): 4674-4689
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gab.com Text
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Perivascular macrophages mediate the neurovascular and cognitive dysfunction
associated with hypertension
#MMPMID27841763
Faraco G
; Sugiyama Y
; Lane D
; Garcia-Bonilla L
; Chang H
; Santisteban MM
; Racchumi G
; Murphy M
; Van Rooijen N
; Anrather J
; Iadecola C
J Clin Invest
2016[Dec]; 126
(12
): 4674-4689
PMID27841763
show ga
Hypertension is a leading risk factor for dementia, but the mechanisms underlying
its damaging effects on the brain are poorly understood. Due to a lack of energy
reserves, the brain relies on continuous delivery of blood flow to its active
regions in accordance with their dynamic metabolic needs. Hypertension disrupts
these vital regulatory mechanisms, leading to the neuronal dysfunction and damage
underlying cognitive impairment. Elucidating the cellular bases of these
impairments is essential for developing new therapies. Perivascular macrophages
(PVMs) represent a distinct population of resident brain macrophages that serves
key homeostatic roles but also has the potential to generate large amounts of
reactive oxygen species (ROS). Here, we report that PVMs are critical in driving
the alterations in neurovascular regulation and attendant cognitive impairment in
mouse models of hypertension. This effect was mediated by an increase in
blood-brain barrier permeability that allowed angiotensin II to enter the
perivascular space and activate angiotensin type 1 receptors in PVMs, leading to
production of ROS through the superoxide-producing enzyme NOX2. These findings
unveil a pathogenic role of PVMs in the neurovascular and cognitive dysfunction
associated with hypertension and identify these cells as a putative therapeutic
target for diseases associated with cerebrovascular oxidative stress.