Chronic oral exposure to the aldehyde pollutant acrolein induces dilated cardiomyopathy

Mohamed Ameen Ismahil, Tariq Hamid, Petra Haberzettl, Yan Gu, Bysani Chandrasekar, Sanjay Srivastava, Aruni Bhatnagar, Sumanth D. Prabhu

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

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 jxl), 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 fac-tor-KB in acrolein-exposed hearts, along with upregulated gene expression of proinflammatory cytokines tumor necrosis factor-a and interleukin-1(3. 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.

Original languageEnglish
Pages (from-to)H2050-H2060
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume301
Issue number5
DOIs
StatePublished - Nov 2011

Keywords

  • Acrolein
  • Cardiomyopathy
  • Environmental pollution
  • Oxidative stress

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