Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; The Institute for Environmental Health Solutions, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
The Center for Environmental Medicine, Asthma and Lung Biology, School of Medicine, The University of North Carolina, Chapel Hill, NC, USA.
Environ Int. 2022 Sep;167:107419. doi: 10.1016/j.envint.2022.107419. Epub 2022 Jul 16.
Wildfires are a threat to public health world-wide that are growing in intensity and prevalence. The biological mechanisms that elicit wildfire-associated toxicity remain largely unknown. The potential involvement of cross-tissue communication via extracellular vesicles (EVs) is a new mechanism that has yet to be evaluated.
Female CD-1 mice were exposed to smoke condensate samples collected from the following biomass burn scenarios: flaming peat; smoldering peat; flaming red oak; and smoldering red oak, representing lab-based simulations of wildfire scenarios. Lung tissue, bronchoalveolar lavage fluid (BALF) samples, peripheral blood, and heart tissues were collected 4 and 24 h post-exposure. Exosome-enriched EVs were isolated from plasma, physically characterized, and profiled for microRNA (miRNA) expression. Pathway-level responses in the lung and heart were evaluated through RNA sequencing and pathway analyses.
Markers of cardiopulmonary tissue injury and inflammation from BALF samples were significantly altered in response to exposures, with the greatest changes occurring from flaming biomass conditions. Plasma EV miRNAs relevant to cardiovascular disease showed exposure-induced expression alterations, including miR-150, miR-183, miR-223-3p, miR-30b, and miR-378a. Lung and heart mRNAs were identified with differential expression enriched for hypoxia and cell stress-related pathways. Flaming red oak exposure induced the greatest transcriptional response in the heart, a large portion of which were predicted as regulated by plasma EV miRNAs, including miRNAs known to regulate hypoxia-induced cardiovascular injury. Many of these miRNAs had published evidence supporting their transfer across tissues. A follow-up analysis of miR-30b showed that it was increased in expression in the heart of exposed mice in the absence of changes to its precursor molecular, pri-miR-30b, suggesting potential transfer from external sources (e.g., plasma).
This study posits a potential mechanism through which wildfire exposures induce cardiopulmonary responses, highlighting the role of circulating plasma EVs in intercellular and systems-level communication between tissues.
野火是全球公共健康的威胁，其强度和普遍性日益增加。引发野火相关毒性的生物学机制在很大程度上尚不清楚。通过细胞外囊泡 (EV) 进行跨组织通讯的潜在作用是一种尚未得到评估的新机制。
雌性 CD-1 小鼠暴露于从以下生物质燃烧情况中收集的烟雾冷凝物样本：燃烧泥炭；闷烧泥炭；燃烧红橡木；闷烧红橡木，代表野火情况的实验室模拟。在暴露后 4 小时和 24 小时收集肺组织、支气管肺泡灌洗液 (BALF) 样本、外周血和心脏组织。从血浆中分离出富含外泌体的 EV ，对其进行物理特征分析，并对 microRNA (miRNA) 表达进行分析。通过 RNA 测序和途径分析评估肺和心脏的途径水平反应。
BALF 样本中的心肺组织损伤和炎症标志物的变化与暴露明显相关，其中燃烧生物质的条件变化最大。与心血管疾病相关的血浆 EV miRNA 的表达改变与暴露诱导有关，包括 miR-150、miR-183、miR-223-3p、miR-30b 和 miR-378a。鉴定出肺和心脏的 mRNAs 表达差异，其富集了缺氧和细胞应激相关途径。红橡木燃烧暴露在心脏中诱导最大的转录反应，其中很大一部分被预测受血浆 EV miRNA 调节，包括已知调节缺氧诱导的心血管损伤的 miRNA。其中许多 miRNA 有支持其在组织间转移的已发表证据。对 miR-30b 的后续分析表明，其在暴露小鼠的心脏中表达增加，而其前体分子 pri-miR-30b 没有变化，这表明它可能来自外部来源（例如，血浆）。
本研究提出了一种野火暴露诱导心肺反应的潜在机制，强调了循环血浆 EV 在组织间和系统水平细胞通讯中的作用。
