Acrolein consumption exacerbates myocardial ischemic injury and blocks nitric oxide-induced PKCε signaling and cardioprotection

Department of Physiology and the Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Journal of Molecular and Cellular Cardiology (Impact Factor: 4.66). 07/2008; 44(6):1016-22. DOI: 10.1016/j.yjmcc.2008.03.020
Source: PubMed


Aldehydes are common reactive constituents of food, water and air. Several food aldehydes are potentially carcinogenic and toxic; however, the direct effects of dietary aldehydes on cardiac ischemia-reperfusion (IR) injury are unknown. We tested the hypothesis that dietary consumption of aldehydes modulates myocardial IR injury and preconditioning. Mice were gavage-fed the alpha, beta-unsaturated aldehyde acrolein (5mg/kg) or water (vehicle) 24h prior to a 30-min coronary artery occlusion and 24-hour reperfusion. Myocardial infarct size was significantly increased in acrolein-treated mice, demonstrating that acute acrolein exposure worsens cardiac IR injury. Furthermore, late cardioprotection afforded by the nitric oxide (NO) donor diethylenetriamine/NO (DETA/NO; dose: 0.1mg/kg x 4, i.v.) was abrogated by the administration of acrolein 2h prior to DETA/NO treatment, indicating that oral acrolein impairs NO donor-induced late preconditioning. To examine potential intracellular targets of aldehydes, we investigated the impact of acrolein on mitochondrial PKCepsilon signaling in the heart. Acrolein-protein adducts were formed in a dose-dependent manner in isolated cardiac mitochondria in vitro and specific acrolein-PKCepsilon adducts were present in cardiac mitochondrial fractions following acrolein exposure in vivo, demonstrating that mitochondria are major targets of aldehyde toxicity. Furthermore, DETA/NO preconditioning induced both PKCepsilon translocation and increased mitochondrial PKCepsilon localization. Both of these responses were blocked by acrolein pretreatment, providing evidence that aldehydes disrupt cardioprotective signaling events involving PKCepsilon. Consumption of an aldehyde-rich diet could exacerbate cardiac IR injury and block NO donor-induced cardioprotection via mechanisms that disrupt PKCepsilon signaling.

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    • "With specific reference to environmental type-2 alkene exposure, research has shown that dietary consumption of acrolein exacerbates myocardial ischemic injury and atherosclerosis in mice by interacting with endogenous unsaturated aldehydes generated during ongoing oxidative stress (Conklin et al. 2010; Ismahil et al. 2011; Luo et al. 2007; Srivastava et al. 2011; Wang et al. 2008). On the basis of these studies it has been proposed that chronic environmental exposure to unsaturated aldehydes is a significant risk factor for cardio vascular diseases (Luo et al. 2007; O'Toole et al. 2008; Wang et al. 2008). Similarly, we have suggested that environmental exposure to a mixture of weak type-2 alkene electrophiles (e.g., ACR, methyl acrylate, ethyl methacrylate ) could accelerate the progressive nerve terminal demise associated with Alzheimer's disease (reviewed by LoPachin et al. 2008b, 2009b). "
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    • "Others have shown that in vitro acrolein is cytotoxic to endothelial cells [9]. In addition, our studies show that oral exposure to acrolein in mice increases the sensitivity of the heart to ischemia-reperfusion injury and abolishes the protective effects of the late phase of ischemic preconditioning [6]. Moreover, recent studies have also reported that oral exposure to acrolein induces hyperlipidemia in mice [5] and activates matrix metalloproteinases (MMPs) by increasing the formation of free radicals in macrophages [10]. "
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