Wu Zhenbiao, He Emily Y, Scott Glenda I, Ren Jun
Department of Clinical Immunology, Xijing Hospital, the Fourth Military Medical University, Xi'an, 710032, China.
Center for Cardiovascular Research and Alternative Medicine, School of Pharmacy, University of Wyoming College of Health Sciences, Laramie, Wyoming, 82071.
Environ Toxicol. 2015 May-Jun;30(6):638-47. doi: 10.1002/tox.21941. Epub 2013 Dec 23.
Air pollution is associated with an increased prevalence of heart disease and is known to trigger a proinflammatory response via stimulation of transient receptor potential vanilloid cation channels (TRPV1, also known as the capsaicin receptor). This study was designed to examine the effect of acrolein, an essential α,β-unsaturated aldehyde pollutant, on myocardial contractile function and the underlying mechanism involved with a focus on TRPV1 and oxidative stress. Cardiomyocyte mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix MyoCam® system including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90 ), fura-2 fluorescence intensity (FFI) and intracellular Ca(2+) decay. Changes in apoptosis and TRPV1 were evaluated using Western blot analysis. The degree of oxidative stress was assessed using the ratio between reduced and oxidized glutathione. Results obtained revealed that exposure of cardiomyocytes to acrolein acutely compromised contractile and intracellular Ca(2+) properties including depressed PS, ± dL/dt and ΔFFI, as well as prolonged TR90 and intracellular Ca(2+) decay. In addition, acrolein exposure upregulated TRPV1 associated with an increase in both apoptosis and oxidative stress. However, the acrolein-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, as well as apoptosis (as evidenced by Bcl-2, Bax, FasL, Caspase-3 and -8), were negated by the reactive oxygen species (ROS) scavenger glutathione or the TRPV1 antagonist capsazepine. Collectively these data suggest that the α,β-unsaturated aldehyde pollutant acrolein may play a role in the pathogenesis and sequelae of air pollution-induced heart disease via a TRPV1- and oxidative stress-dependent mechanism.
空气污染与心脏病患病率增加有关，并且已知其通过刺激瞬时受体电位香草酸阳离子通道（TRPV1，也称为辣椒素受体）引发促炎反应。本研究旨在探讨丙烯醛（一种重要的α，β-不饱和醛污染物）对心肌收缩功能的影响以及潜在机制，重点关注TRPV1和氧化应激。使用IonOptix MyoCam®系统评估心肌细胞的机械性能和细胞内Ca(2+)特性，包括峰值缩短（PS）、缩短/再延长的最大速度（±dL/dt）、达到PS的时间（TPS）、达到90%再延长的时间（TR90）、fura-2荧光强度（FFI）和细胞内Ca(2+)衰减。使用蛋白质印迹分析评估细胞凋亡和TRPV1的变化。使用还原型谷胱甘肽与氧化型谷胱甘肽的比率评估氧化应激程度。所得结果显示，心肌细胞暴露于丙烯醛会急性损害收缩功能和细胞内Ca(2+)特性，包括PS降低、±dL/dt和ΔFFI降低，以及TR90和细胞内Ca(2+)衰减延长。此外，丙烯醛暴露上调TRPV1，同时细胞凋亡和氧化应激增加。然而，活性氧（ROS）清除剂谷胱甘肽或TRPV1拮抗剂辣椒素可消除丙烯醛诱导的心肌细胞收缩和细胞内Ca(2+)异常以及细胞凋亡（通过Bcl-2、Bax、FasL、Caspase-3和-8证明）。总体而言，这些数据表明α，β-不饱和醛污染物丙烯醛可能通过TRPV1和氧化应激依赖性机制在空气污染诱发的心脏病的发病机制和后遗症中发挥作用。
