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

Darcy Lidington; Jessica C. Fares; Franziska E. Uhl; Danny D. Dinh; Jeffrey T. Kroetsch; Meghan Sauvé; Firhan A. Malik; Frank Matthes; Lotte Vanherle; Arman Adel; Abdul Momen; Hangjun Zhang; Roozbeh Aschar-Sobbi; Warren D. Foltz; Hoyee Wan; Manabu Sumiyoshi; R. Loch Macdonald; Mansoor Husain; Peter H. Backx; Scott P. Heximer; Anja Meissner; Steffen Sebastian Bolz

doi:10.1016/j.jacbts.2019.07.004

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

Darcy Lidington, Jessica C. Fares, Franziska E. Uhl, Danny D. Dinh, Jeffrey T. Kroetsch, Meghan Sauvé, Firhan A. Malik, Frank Matthes, Lotte Vanherle, Arman Adel, Abdul Momen, Hangjun Zhang, Roozbeh Aschar-Sobbi, Warren D. Foltz, Hoyee Wan, Manabu Sumiyoshi, R. Loch Macdonald, Mansoor Husain, Peter H. Backx, Scott P. HeximerAnja Meissner, Steffen Sebastian Bolz

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Sammanfattning

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.

Originalspråk	engelska
Sidor (från-till)	940-958
Antal sidor	19
Tidskrift	JACC: Basic to Translational Science
Volym	4
Nummer	8
DOI	https://doi.org/10.1016/j.jacbts.2019.07.004
Status	Published - 2019

Ämnesklassifikation (UKÄ)

Kardiologi

Tillgång till dokument

10.1016/j.jacbts.2019.07.004

Citera det här

Lidington, D., Fares, J. C., Uhl, F. E., Dinh, D. D., Kroetsch, J. T., Sauvé, M., Malik, F. A., Matthes, F., Vanherle, L., Adel, A., Momen, A., Zhang, H., Aschar-Sobbi, R., Foltz, W. D., Wan, H., Sumiyoshi, M., Macdonald, R. L., Husain, M., Backx, P. H., ... Bolz, S. S. (2019). CFTR Therapeutics Normalize Cerebral Perfusion Deficits in Mouse Models of Heart Failure and Subarachnoid Hemorrhage. JACC: Basic to Translational Science, 4(8), 940-958. https://doi.org/10.1016/j.jacbts.2019.07.004

@article{03a1fe8faffb44d8aeb6c1803cafed4f,

title = "CFTR Therapeutics Normalize Cerebral Perfusion Deficits in Mouse Models of Heart Failure and Subarachnoid Hemorrhage",

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 perfusion, and neuronal injury.",

keywords = "cognitive impairment, corrector compounds, cystic fibrosis transmembrane conductance regulator (CFTR), myogenic vasoconstriction, sphingosine-1-phosphate, tumor necrosis factor, vascular smooth muscle cells",

author = "Darcy Lidington and Fares, {Jessica C.} and Uhl, {Franziska E.} and Dinh, {Danny D.} and Kroetsch, {Jeffrey T.} and Meghan Sauv{\'e} and Malik, {Firhan A.} and Frank Matthes and Lotte Vanherle and Arman Adel and Abdul Momen and Hangjun Zhang and Roozbeh Aschar-Sobbi and Foltz, {Warren D.} and Hoyee Wan and Manabu Sumiyoshi and Macdonald, {R. Loch} and Mansoor Husain and Backx, {Peter H.} and Heximer, {Scott P.} and Anja Meissner and Bolz, {Steffen Sebastian}",

year = "2019",

doi = "10.1016/j.jacbts.2019.07.004",

language = "English",

volume = "4",

pages = "940--958",

journal = "JACC: Basic to Translational Science",

issn = "2452-302X",

publisher = "Elsevier",

number = "8",

}

Lidington, D, Fares, JC, Uhl, FE, Dinh, DD, Kroetsch, JT, Sauvé, M, Malik, FA, Matthes, F , Vanherle, L, Adel, A, Momen, A, Zhang, H, Aschar-Sobbi, R, Foltz, WD, Wan, H, Sumiyoshi, M, Macdonald, RL, Husain, M, Backx, PH, Heximer, SP, Meissner, A & Bolz, SS 2019, 'CFTR Therapeutics Normalize Cerebral Perfusion Deficits in Mouse Models of Heart Failure and Subarachnoid Hemorrhage', JACC: Basic to Translational Science, vol. 4, nr. 8, s. 940-958. https://doi.org/10.1016/j.jacbts.2019.07.004

TY - JOUR

T1 - CFTR Therapeutics Normalize Cerebral Perfusion Deficits in Mouse Models of Heart Failure and Subarachnoid Hemorrhage

AU - Lidington, Darcy

AU - Fares, Jessica C.

AU - Uhl, Franziska E.

AU - Dinh, Danny D.

AU - Kroetsch, Jeffrey T.

AU - Sauvé, Meghan

AU - Malik, Firhan A.

AU - Matthes, Frank

AU - Vanherle, Lotte

AU - Adel, Arman

AU - Momen, Abdul

AU - Zhang, Hangjun

AU - Aschar-Sobbi, Roozbeh

AU - Foltz, Warren D.

AU - Wan, Hoyee

AU - Sumiyoshi, Manabu

AU - Macdonald, R. Loch

AU - Husain, Mansoor

AU - Backx, Peter H.

AU - Heximer, Scott P.

AU - Meissner, Anja

AU - Bolz, Steffen Sebastian

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - cognitive impairment

KW - corrector compounds

KW - cystic fibrosis transmembrane conductance regulator (CFTR)

KW - myogenic vasoconstriction

KW - sphingosine-1-phosphate

KW - tumor necrosis factor

KW - vascular smooth muscle cells

U2 - 10.1016/j.jacbts.2019.07.004

DO - 10.1016/j.jacbts.2019.07.004

M3 - Article

C2 - 31909302

AN - SCOPUS:85076713902

VL - 4

SP - 940

EP - 958

JO - JACC: Basic to Translational Science

JF - JACC: Basic to Translational Science

SN - 2452-302X

IS - 8

ER -

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

Sammanfattning

Ämnesklassifikation (UKÄ)

Tillgång till dokument

Fingeravtryck

Citera det här