Chronic oral exposure to the aldehyde pollutant acrolein induces dilated cardiomyopathy
Chronic oral exposure to the aldehyde pollutant acrolein induces dilated cardiomyopathy
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DOI：
10.1152/ajpheart.00120.2011
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发表时间：
2011-11-01
影响因子：
4.8
通讯作者：
Prabhu, Sumanth D.
中科院分区：
文献类型：
--
作者：
Ismahil, Mohamed Ameen;Hamid, Tariq;Prabhu, Sumanth D.
Ismahil MA，Hamid T，Haberzettl P，Gu Y，Srirasekar B，Srivastava S，Bhatnagar A，Prabhu SD.慢性经口暴露于醛类污染物丙烯醛诱发扩张型心肌病。Am J Physiol Heart Circ Physiol 301：H2050-H2060，2011.首次发表于2011年9月9日; doi：10.1152/ajpheart.00120.2011。扩张型心肌病的环境触发因素知之甚少。丙烯醛是一种普遍存在的醛类污染物，急性暴露于丙烯醛会损害小鼠的心脏功能和心脏保护反应。在这里，我们测试的假设，慢性口服暴露于丙烯醛诱导炎症和心肌病。C57 BL/6小鼠每天灌胃丙烯醛（1 mg/kg）或水（溶剂），持续48天。根据人体每日不饱和醛消耗量的估计值选择剂量。与媒介物喂养的小鼠相比，丙烯醛喂养的小鼠表现出显著的左室扩张（P < 0.05）（LV舒张末期容积36 +/- 8 vs. 17 +/- 5 mu l），收缩功能障碍（dP/dt（max）4，697 +/-1，498 vs. 7，016 +/-1，757 mmHg/s）和舒张受损（tau 15.4 +/- 4.3 vs. 10.4 +/- 2.2 ms）。组织学和生物化学评价显示心肌氧化应激（膜定位蛋白质-4-羟基-反式-2-壬烯醛加合物）和硝化应激（蛋白质-硝基酪氨酸增加）以及不同程度的血浆和心肌蛋白质-丙烯醛加合物形成，表明摄入的丙烯醛物理易位至心脏。丙烯醛还诱导心肌细胞肥大（类似于心肌细胞面积增加2.2倍，P < 0.05），细胞凋亡增加（类似于7.5倍），并破坏心脏中的内皮型一氧化氮合酶。DNA结合研究、免疫组织化学和PCR显示，丙烯醛暴露心脏中核因子-κ B显著（P < 0.05）活化，沿着促炎细胞因子肿瘤坏死因子-α和白细胞介素-1 β的基因表达上调。长期口服暴露于丙烯醛，在人类不饱和醛摄入量的范围内，诱导小鼠扩张型心肌病的表型。人类暴露于丙烯醛可能有类似的影响，并提出考虑的环境，糖介导的基础心力衰竭。
Ismahil MA, Hamid T, Haberzettl P, Gu Y, Chandrasekar B, Srivastava S, Bhatnagar A, Prabhu SD. Chronic oral exposure to the aldehyde pollutant acrolein induces dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 301: H2050-H2060, 2011. First published September 9, 2011; doi:10.1152/ajpheart.00120.2011.-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 mu l), 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 (similar to 2.2-fold increased myocyte area, P < 0.05), increased apoptosis (similar to 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-kappa B in acrolein-exposed hearts, along with upregulated gene expression of proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1 beta. 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.