Epigenetic Regulation in Particulate Matter-Mediated Cardiopulmonary Toxicities: A Systems Biology Perspective.
Epigenetic Regulation in Particulate Matter-Mediated Cardiopulmonary Toxicities: A Systems Biology Perspective.
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DOI：
10.2174/187569212803901792
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发表时间：
2012-12
影响因子：
--
通讯作者：
Zhang W
中科院分区：
文献类型：
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作者：
Wang T;Garcia JG;Zhang W
颗粒物（PM）空气污染对全球人口的健康产生重大不利影响，特别是在空气污染严重的发展中国家。对PM引起的健康影响（包括心血管疾病风险）的机制的理解仍然有限。除了直接的细胞生理反应，如线粒体功能障碍和氧化应激，PM介导显着的基因表达失调，特别是在心血管组织。PM介导的基因失调可能是一个受多种遗传和非遗传因素影响的复杂机制。值得注意的是，已知PM改变表观遗传标记（例如，DNA甲基化和组蛋白修饰），这可能导致空气污染介导的健康后果，包括心血管疾病的风险。值得注意的是，由环境PM暴露引起的表观遗传变化已经出现在基因调控中发挥关键作用。虽然其机制尚不完全清楚，但已有证据表明，DNA甲基转移酶（DNMT）、组蛋白乙酰化酶（HAT）和组蛋白去乙酰化酶（HDAC）的活性调节可能有助于PM或PM相关化学物质诱导的表观遗传变化。通过采用全基因组表观基因组学和系统生物学方法，PM毒理基因组学可以想象地取得很大进展，与PM暴露后基因表达失调相关的单个表观遗传位点的潜在鉴定，以及表观遗传途径与PM之间的相互作用。此外，基于表观遗传标记的新型治疗靶点可以通过未来对PM介导的心肺毒性的表观基因组研究来确定。这些考虑共同为基因组学在发展中国家未来的人口健康应用提供了信息，同时使全球个性化医疗受益。
Particulate matter (PM) air pollution exerts significant adverse health effects in global populations, particularly in developing countries with extensive air pollution. Understanding of the mechanisms of PM-induced health effects including the risk for cardiovascular diseases remains limited. In addition to the direct cellular physiological responses such as mitochondrial dysfunction and oxidative stress, PM mediates remarkable dysregulation of gene expression, especially in cardiovascular tissues. The PM-mediated gene dysregulation is likely to be a complex mechanism affected by various genetic and non-genetic factors. Notably, PM is known to alter epigenetic markers (e.g., DNA methylation and histone modifications), which may contribute to air pollution-mediated health consequences including the risk for cardiovascular diseases. Notably, epigenetic changes induced by ambient PM exposure have emerged to play a critical role in gene regulation. Though the underlying mechanism(s) are not completely clear, the available evidence suggests that the modulated activities of DNA methyltransferase (DNMT), histone acetylase (HAT) and histone deacetylase (HDAC) may contribute to the epigenetic changes induced by PM or PM-related chemicals. By employing genome-wide epigenomic and systems biology approaches, PM toxicogenomics could conceivably progress greatly with the potential identification of individual epigenetic loci associated with dysregulated gene expression after PM exposure, as well the interactions between epigenetic pathways and PM. Furthermore, novel therapeutic targets based on epigenetic markers could be identified through future epigenomic studies on PM-mediated cardiopulmonary toxicities. These considerations collectively inform the future population health applications of genomics in developing countries while benefiting global personalized medicine at the same time.