The Center for Computational Toxicology and Exposure, US Environmental Protection Agency, Durham, NC, 27711, USA.
Center for Public Health and Environmental Assessment, US Environmental Protection Agency, Durham, NC, 27711, USA.
Cardiovasc Toxicol. 2024 Dec;24(12):1348-1363. doi: 10.1007/s12012-024-09931-9. Epub 2024 Oct 14.
Inhalation of ambient particulate matter (PM) and ozone (O) has been associated with increased cardiovascular morbidity and mortality. However, the interactive effects of PM and O on cardiac dysfunction and disease have not been thoroughly examined, especially at a proteomic level. The purpose of this study was to identify and compare proteome changes in spontaneously hypertensive (SH) rats co-exposed to concentrated ambient particulates (CAPs) and O, with a focus on investigating inflammatory and metabolic pathways, which are the two major ones implicated in the pathophysiology of cardiac dysfunction. For this, we measured and compared changes in expression status of 9 critical pro- and anti-inflammatory cytokines using multiplexed ELISA and 450 metabolic proteins involved in ATP production, oxidative phosphorylation, cytoskeletal organization, and stress response using two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) in cardiac tissue of SH rats exposed to CAPs alone, O alone, and CAPs + O. Proteomic expression profiling revealed that CAPs alone, O alone, and CAPs + O differentially altered protein expression patterns, and utilized divergent mechanisms to affect inflammatory and metabolic pathways and responses. Ingenuity Pathway Analysis (IPA) of the proteomic data demonstrated that the metabolic protein network centered by gap junction alpha-1 protein (GJA 1) was interconnected with the inflammatory cytokine network centered by nuclear factor kappa beta (NF-kB) potentially suggesting inflammation-induced alterations in metabolic pathways, or vice versa, collectively contributing to the development of cardiac dysfunction in response to CAPs and O exposure. These findings may enhance understanding of the pathophysiology of cardiac dysfunction induced by air pollution and provide testable hypotheses regarding mechanisms of action.
环境颗粒物（PM）和臭氧（O）的吸入与心血管发病率和死亡率的增加有关。然而，PM 和 O 对心脏功能障碍和疾病的相互作用影响尚未得到彻底研究，特别是在蛋白质组学水平上。本研究的目的是鉴定和比较共暴露于浓缩环境颗粒物（CAPs）和 O 的自发性高血压（SH）大鼠的蛋白质组变化，重点研究炎症和代谢途径，这两个途径与心脏功能障碍的病理生理学密切相关。为此，我们使用多重 ELISA 测量和比较了 9 种关键促炎和抗炎细胞因子的表达状态变化，并使用二维电泳（2-DE）和质谱（MS）比较了心脏组织中涉及 ATP 产生、氧化磷酸化、细胞骨架组织和应激反应的 450 种代谢蛋白的表达状态变化，以比较 CAPs 单独暴露、O 单独暴露和 CAPs+O 暴露的 SH 大鼠。蛋白质组表达谱分析显示，CAPs 单独暴露、O 单独暴露和 CAPs+O 差异改变了蛋白质表达模式，并利用不同的机制影响炎症和代谢途径和反应。蛋白质组学数据的 IPA 分析表明，以间隙连接蛋白α-1（GJA1）为中心的代谢蛋白网络与以核因子 kappa beta（NF-kB）为中心的炎症细胞因子网络相互连接，这可能表明炎症引起的代谢途径改变，或者相反，共同导致对 CAPs 和 O 暴露的心脏功能障碍的发展。这些发现可能有助于增强对空气污染引起的心脏功能障碍的病理生理学的理解，并提供有关作用机制的可测试假设。
