title: α,β-Unsaturated aldehyde pollutant acrolein suppresses cardiomyocyte contractile function: Role of TRPV1 and oxidative stress.
abstract: Air pollution is associated with an increased prevalence of heart disease and is known to trigger a proinflammatory response via stimulation of transient receptor potential vanilloid cation channels (TRPV1, also known as the capsaicin receptor). This study was designed to examine the effect of acrolein, an essential α,β-unsaturated aldehyde pollutant, on myocardial contractile function and the underlying mechanism involved with a focus on TRPV1 and oxidative stress. Cardiomyocyte mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix MyoCam® system including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90 ), fura-2 fluorescence intensity (FFI) and intracellular Ca(2+) decay. Changes in apoptosis and TRPV1 were evaluated using Western blot analysis. The degree of oxidative stress was assessed using the ratio between reduced and oxidized glutathione. Results obtained revealed that exposure of cardiomyocytes to acrolein acutely compromised contractile and intracellular Ca(2+) properties including depressed PS, ± dL/dt and ΔFFI, as well as prolonged TR90 and intracellular Ca(2+) decay. In addition, acrolein exposure upregulated TRPV1 associated with an increase in both apoptosis and oxidative stress. However, the acrolein-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, as well as apoptosis (as evidenced by Bcl-2, Bax, FasL, Caspase-3 and -8), were negated by the reactive oxygen species (ROS) scavenger glutathione or the TRPV1 antagonist capsazepine. Collectively these data suggest that the α,β-unsaturated aldehyde pollutant acrolein may play a role in the pathogenesis and sequelae of air pollution-induced heart disease via a TRPV1- and oxidative stress-dependent mechanism.
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, the Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Zhenbiao
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, the Fourth Military Medical University, Xi'an, 710032, China.|Center for Cardiovascular Research and Alternative Medicine, School of Pharmacy, University of Wyoming College of Health Sciences, Laramie, Wyoming, 82071.
authors.forename: Emily Y
authors.initials: EY
authors.lastname: He
authors.affiliation: Center for Cardiovascular Research and Alternative Medicine, School of Pharmacy, University of Wyoming College of Health Sciences, Laramie, Wyoming, 82071.
authors.forename: Glenda I
authors.initials: GI
authors.lastname: Scott
authors.affiliation: Center for Cardiovascular Research and Alternative Medicine, School of Pharmacy, University of Wyoming College of Health Sciences, Laramie, Wyoming, 82071.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
mesh_terms: D000171:Acrolein / Q000633:toxicity*; D000447:Aldehydes; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D004785:Environmental Pollutants; D017382:Reactive Oxygen Species; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D000171:Acrolein; D053148:Caspase 3; D005978:Glutathione; D002118:Calcium
keywords: TRPV1; acrolein; cardiomyocytes; contractile function; oxidative stress