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Epigenetic Regulation in Particulate Matter-Mediated Cardiopulmonary Toxicities: A Systems Biology Perspective

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journal contribution
posted on 26.11.2013, 00:00 authored by Ting Wang, Joe GN Garcia, Wei Zhang
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 2 collectively inform the future population health applications of genomics in developing countries while benefiting global personalized medicine at the same time.

Funding

This work was partially supported by NIH R21HG006367 (to WZ) and Parker B Francis Fellowship (to TW).

History

Publisher Statement

This is a copy of an article published in the Current Pharmacogenomics and Personalized Medicine © 2012 Bentham Science Publishers. The final publication is available at www.benthamscience.com/cppm/index.htm

Publisher

Bentham Science Publishers

Language

en_US

issn

1875-6921

Issue date

01/11/2012