title: An Oral Selective Alpha-1A Adrenergic Receptor Agonist Prevents Doxorubicin Cardiotoxicity.
abstract: α1A-ARs play adaptive and protective roles in the heart. Dabuzalgron is an oral selective α1A-AR agonist that was well tolerated in multiple clinical trials of treatment for urinary incontinence, but has never been used to treat heart disease in humans or animal models. In this study, we administered dabuzalgron to mice treated with DOX, a widely used chemotherapeutic agent with dose-limiting cardiotoxicity that can lead to HF. Dabuzalgron protected against DOX-induced cardiotoxicity, likely by preserving mitochondrial function. These results suggest that activating cardiac α1A-ARs with dabuzalgron, a well-tolerated oral agent, might represent a novel approach to treating HF.
authors.affiliation: University of North Carolina School of Medicine, McAllister Heart Institute.
authors.forename: JuYoun
authors.initials: J
authors.lastname: Beak
authors.affiliation: University of North Carolina School of Medicine, McAllister Heart Institute.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: UNC School of Medicine, Lineberger Cancer Center; UNC School of Medicine, Department of Genetics.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Parker
authors.affiliation: University of North Carolina School of Medicine, McAllister Heart Institute.
authors.forename: Sean T
authors.initials: ST
authors.lastname: Hicks
authors.affiliation: Weill-Cornell Medical College Department of Medicine.
authors.forename: Cam
authors.initials: C
authors.lastname: Patterson
authors.affiliation: Department of Medicine and Research Service, San Francisco VA Medical Center and Cardiovascular Research Institute, University of California, San Francisco.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Simpson
authors.affiliation: Departments of Structural and Chemical Biology, Oncological Sciences, and Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai.
authors.forename: Anqi
authors.initials: A
authors.lastname: Ma
authors.affiliation: Departments of Structural and Chemical Biology, Oncological Sciences, and Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai.
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.affiliation: University of North Carolina School of Medicine, McAllister Heart Institute; UNC School of Medicine, Division of Cardiology.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Jensen
keywords: adrenergic; alpha; anthracyclines; cardioprotection; catecholamines; heart failure; receptors