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.

Protection of HepG2 cells against acrolein toxicity by 2-cyano-3,12-dioxooleana-1,9-dien-28-imidazolide via glutathione-mediated mechanism

“…50 Interestingly, acrolein is both an initiator and an end-product of lipid peroxidation. It has been suggested that acrolein causes the alteration of target molecules via oxidative stress, generation of excess reactive oxygen species, and alteration of endogenous antioxidants, such as depletion in GSH level in target cells.…”

Electronic Cigarettes

“…The heating of glycerol can form acrolein, which is an irritant and oxidizing agent thought to contribute to adverse pulmonary and cardiovascular effects of cigarette smoking. [83][84][85] Analyses of emissions from cigarettes have found primarily formaldehyde, acetaldehyde, and acrolein, along with low levels of toluene, xylene, benzene, and butadiene. 86 Although these compounds are potentially toxic, the levels in e-cigarette emissions are many-fold lower than those found in cigarette smoke and in some cases similar to those found in the mist of medicinal nicotine inhalers.…”

Ambient and household air pollution: complex triggers of disease

“…The study found 2,879 differentially expressed genes of the 45,037 transcripts in the microarray, highlighting the potential influence of synthetic musk on embryonic development. Another study (34) showed that chronic oral exposure to acrolein, an aldehyde pollutant, caused dilated cardiomyopathy in mice. The effects of human exposure to acrolein should be studied further to investigate possible connections between chronic exposure, cardiomyopathy, and heart failure.…”