title: Carbon monoxide pollution aggravates ischemic heart failure through oxidative stress pathway.
abstract: Risk of hospital readmission and cardiac mortality increases with atmospheric pollution for patients with heart failure. The underlying mechanisms are unclear. Carbon monoxide (CO) a ubiquitous environmental pollutant could be involved. We explored the effect of daily exposure of CO relevant to urban pollution on post-myocardial infarcted animals. Rats with ischemic heart failure were exposed 4 weeks to daily peaks of CO mimicking urban exposure or to standard filtered air. CO exposure worsened cardiac contractile dysfunction evaluated by echocardiography and at the cardiomyocyte level. In line with clinical reports, the animals exposed to CO also exhibited a severe arrhythmogenic phenotype with numerous sustained ventricular tachycardias as monitored by surface telemetric electrocardiograms. CO did not affect cardiac β-adrenergic responsiveness. Instead, mitochondrial dysfunction was exacerbated leading to additional oxidative stress and Ca2+cycling alterations. This was reversed following acute antioxidant treatment of cardiomyocytes with N-acetylcysteine confirming involvement of CO-induced oxidative stress. Exposure to daily peaks of CO pollution aggravated cardiac dysfunction in rats with ischemic heart failure by specifically targeting mitochondria and generating ROS-dependent alterations. This pathway may contribute to the high sensibility and vulnerability of individuals with cardiac disease to environmental outdoor air quality.
authors.affiliation: LAPEC EA4278, Université Avignon, Avignon, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Reboul
authors.affiliation: LAPEC EA4278, Université Avignon, Avignon, France.|INSERM U1046, CNRS UMR 9214, Université Montpellier, Montpellier, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Boissière
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université Montpellier, Montpellier, France.
authors.forename: Lucas
authors.initials: L
authors.lastname: André
authors.affiliation: LAPEC EA4278, Université Avignon, Avignon, France.
authors.forename: Gregory
authors.initials: G
authors.lastname: Meyer
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université Montpellier, Montpellier, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Bideaux
authors.affiliation: INRA UMR 866, Unité Dynamique Musculaire et Métabolisme, Montpellier, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Fouret
authors.affiliation: INRA UMR 866, Unité Dynamique Musculaire et Métabolisme, Montpellier, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Feillet-Coudray
authors.affiliation: LAPEC EA4278, Université Avignon, Avignon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Obert
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université Montpellier, Montpellier, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Lacampagne
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université Montpellier, Montpellier, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Thireau
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université Montpellier, Montpellier, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cazorla
authors.affiliation: INSERM U1046, CNRS UMR 9214, Université Montpellier, Montpellier, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Richard
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002248:Carbon Monoxide / Q000009:adverse effects / Q000378:metabolism*; D003331:Coronary Vessels / Q000601:surgery*; D004195:Disease Models, Animal; D004562:Electrocardiography; D004781:Environmental Exposure / Q000009:adverse effects; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000393:Air Pollutants; D017382:Reactive Oxygen Species; D002248:Carbon Monoxide; D002118:Calcium