Chronic oral exposure to the aldehyde pollutant acrolein induces dilated cardiomyopathy.

Academic Article

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.
  • Keywords

  • Acrolein, Administration, Oral, Animals, Apoptosis, Cardiomyopathy, Dilated, Environmental Pollutants, Gene Expression Regulation, Hypertrophy, Left Ventricular, Immunohistochemistry, Inflammation Mediators, Male, Mice, Mice, Inbred C57BL, Myocardial Contraction, Myocarditis, Myocardium, Oxidative Stress, Real-Time Polymerase Chain Reaction, Time Factors, Ventricular Dysfunction, Left, Ventricular Function, Left, Ventricular Remodeling
  • Digital Object Identifier (doi)

    Author List

  • Ismahil MA; Hamid T; Haberzettl P; Gu Y; Chandrasekar B; Srivastava S; Bhatnagar A; Prabhu SD
  • Start Page

  • H2050
  • End Page

  • H2060
  • Volume

  • 301
  • Issue

  • 5