1. CFTR Therapeutics Normalize Cerebral Perfusion Deficits in Mouse Models of Heart Failure and Subarachnoid Hemorrhage
- Author
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Darcy Lidington, PhD, Jessica C. Fares, MSc, Franziska E. Uhl, PhD, Danny D. Dinh, MSc, Jeffrey T. Kroetsch, PhD, Meghan Sauvé, PhD, Firhan A. Malik, PhD, Frank Matthes, PhD, Lotte Vanherle, MSc, Arman Adel, BSc, Abdul Momen, MD, PhD, Hangjun Zhang, MD, Roozbeh Aschar-Sobbi, PhD, Warren D. Foltz, PhD, Hoyee Wan, BSc, Manabu Sumiyoshi, MD, R. Loch Macdonald, MD, PhD, Mansoor Husain, MD, Peter H. Backx, PhD, DVM, Scott P. Heximer, PhD, Anja Meissner, PhD, and Steffen-Sebastian Bolz, MD, PhD
- Subjects
Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Summary: 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. Key Words: cognitive impairment, corrector compounds, cystic fibrosis transmembrane conductance regulator (CFTR), myogenic vasoconstriction, sphingosine-1-phosphate, tumor necrosis factor, vascular smooth muscle cells
- Published
- 2019
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