title: Chronic oral exposure to the aldehyde pollutant acrolein induces dilated cardiomyopathy.
abstract: Environmental triggers of dilated cardiomyopathy are poorly understood. Acute exposure to acrolein, a ubiquitous aldehyde pollutant, impairs cardiac function and cardioprotective responses in mice. Here, we tested the hypothesis that chronic oral exposure to acrolein induces inflammation and cardiomyopathy. C57BL/6 mice were gavage-fed acrolein (1 mg/kg) or water (vehicle) daily for 48 days. The dose was chosen based on estimates of human daily unsaturated aldehyde consumption. Compared with vehicle-fed mice, acrolein-fed mice exhibited significant (P < 0.05) left ventricular (LV) dilatation (LV end-diastolic volume 36 ± 8 vs. 17 ± 5 μl), contractile dysfunction (dP/dt(max) 4,697 ± 1,498 vs. 7,016 ± 1,757 mmHg/s), and impaired relaxation (tau 15.4 ± 4.3 vs. 10.4 ± 2.2 ms). Histological and biochemical evaluation revealed myocardial oxidative stress (membrane-localized protein-4-hydroxy-trans-2-nonenal adducts) and nitrative stress (increased protein-nitrotyrosine) and varying degrees of plasma and myocardial protein-acrolein adduct formation indicative of physical translocation of ingested acrolein to the heart. Acrolein also induced myocyte hypertrophy (~2.2-fold increased myocyte area, P < 0.05), increased apoptosis (~7.5-fold), and disrupted endothelial nitric oxide synthase in the heart. DNA binding studies, immunohistochemistry, and PCR revealed significant (P < 0.05) activation of nuclear factor-κB in acrolein-exposed hearts, along with upregulated gene expression of proinflammatory cytokines tumor necrosis factor-α and interleukin-1β. Long-term oral exposure to acrolein, at an amount within the range of human unsaturated aldehyde intake, induces a phenotype of dilated cardiomyopathy in the mouse. Human exposure to acrolein may have analogous effects and raise consideration of an environmental, aldehyde-mediated basis for heart failure.
authors: Department of Medicine, Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40202, USA.
authors: Mohamed Ameen
authors: MA
authors: Ismahil
authors: Tariq
authors: T
authors: Hamid
authors: Petra
authors: P
authors: Haberzettl
authors: Yan
authors: Y
authors: Gu
authors: Bysani
authors: B
authors: Chandrasekar
authors: Sanjay
authors: S
authors: Srivastava
authors: Aruni
authors: A
authors: Bhatnagar
authors: Sumanth D
authors: SD
authors: Prabhu
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000187:drug effects; D009205:Myocarditis / Q000139:chemically induced; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D004785:Environmental Pollutants; D018836:Inflammation Mediators; D000171:Acrolein