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CFTR Therapeutics Normalize Cerebral Perfusion Deficits in Mouse Models of Heart Failure and Subarachnoid Hemorrhage

Lidington, Darcy ; Fares, Jessica C. ; Uhl, Franziska E. LU ; Dinh, Danny D. ; Kroetsch, Jeffrey T. ; Sauvé, Meghan ; Malik, Firhan A. ; Matthes, Frank LU ; Vanherle, Lotte LU and Adel, Arman , et al. (2019) In JACC: Basic to Translational Science 4(8). p.940-958
Abstract

Heart failure (HF) and subarachnoid hemorrhage (SAH) chronically reduce cerebral perfusion, which negatively affects clinical outcome. This work demonstrates a strong relationship between cerebral artery cystic fibrosis transmembrane conductance regulator (CFTR) expression and altered cerebrovascular reactivity in HF and SAH. In HF and SAH, CFTR corrector compounds (C18 or lumacaftor) normalize pathological alterations in cerebral artery CFTR expression, vascular reactivity, and cerebral perfusion, without affecting systemic hemodynamic parameters. This normalization correlates with reduced neuronal injury. Therefore, CFTR therapeutics have emerged as valuable clinical tools to manage cerebrovascular dysfunction, impaired cerebral... (More)

Heart failure (HF) and subarachnoid hemorrhage (SAH) chronically reduce cerebral perfusion, which negatively affects clinical outcome. This work demonstrates a strong relationship between cerebral artery cystic fibrosis transmembrane conductance regulator (CFTR) expression and altered cerebrovascular reactivity in HF and SAH. In HF and SAH, CFTR corrector compounds (C18 or lumacaftor) normalize pathological alterations in cerebral artery CFTR expression, vascular reactivity, and cerebral perfusion, without affecting systemic hemodynamic parameters. This normalization correlates with reduced neuronal injury. Therefore, CFTR therapeutics have emerged as valuable clinical tools to manage cerebrovascular dysfunction, impaired cerebral perfusion, and neuronal injury.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cognitive impairment, corrector compounds, cystic fibrosis transmembrane conductance regulator (CFTR), myogenic vasoconstriction, sphingosine-1-phosphate, tumor necrosis factor, vascular smooth muscle cells
in
JACC: Basic to Translational Science
volume
4
issue
8
pages
19 pages
publisher
Elsevier
external identifiers
  • scopus:85076713902
  • pmid:31909302
ISSN
2452-302X
DOI
10.1016/j.jacbts.2019.07.004
language
English
LU publication?
yes
id
03a1fe8f-affb-44d8-aeb6-c1803cafed4f
date added to LUP
2020-01-08 14:28:58
date last changed
2024-07-10 08:35:40
@article{03a1fe8f-affb-44d8-aeb6-c1803cafed4f,
  abstract     = {{<p>Heart failure (HF) and subarachnoid hemorrhage (SAH) chronically reduce cerebral perfusion, which negatively affects clinical outcome. This work demonstrates a strong relationship between cerebral artery cystic fibrosis transmembrane conductance regulator (CFTR) expression and altered cerebrovascular reactivity in HF and SAH. In HF and SAH, CFTR corrector compounds (C18 or lumacaftor) normalize pathological alterations in cerebral artery CFTR expression, vascular reactivity, and cerebral perfusion, without affecting systemic hemodynamic parameters. This normalization correlates with reduced neuronal injury. Therefore, CFTR therapeutics have emerged as valuable clinical tools to manage cerebrovascular dysfunction, impaired cerebral perfusion, and neuronal injury.</p>}},
  author       = {{Lidington, Darcy and Fares, Jessica C. and Uhl, Franziska E. and Dinh, Danny D. and Kroetsch, Jeffrey T. and Sauvé, Meghan and Malik, Firhan A. and Matthes, Frank and Vanherle, Lotte and Adel, Arman and Momen, Abdul and Zhang, Hangjun and Aschar-Sobbi, Roozbeh and Foltz, Warren D. and Wan, Hoyee and Sumiyoshi, Manabu and Macdonald, R. Loch and Husain, Mansoor and Backx, Peter H. and Heximer, Scott P. and Meissner, Anja and Bolz, Steffen Sebastian}},
  issn         = {{2452-302X}},
  keywords     = {{cognitive impairment; corrector compounds; cystic fibrosis transmembrane conductance regulator (CFTR); myogenic vasoconstriction; sphingosine-1-phosphate; tumor necrosis factor; vascular smooth muscle cells}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{940--958}},
  publisher    = {{Elsevier}},
  series       = {{JACC: Basic to Translational Science}},
  title        = {{CFTR Therapeutics Normalize Cerebral Perfusion Deficits in Mouse Models of Heart Failure and Subarachnoid Hemorrhage}},
  url          = {{http://dx.doi.org/10.1016/j.jacbts.2019.07.004}},
  doi          = {{10.1016/j.jacbts.2019.07.004}},
  volume       = {{4}},
  year         = {{2019}},
}