期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 184, 期 1, 页码 82-91出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.201012-1967OC
关键词
atherosclerosis; particulate matter; endothelin-1; matrix metalloproteinase; oxidized low-density lipoprotein
资金
- National Institute of Environmental Health Sciences [R00ES016586, R01ES014639]
- Health Effects Institute [EPA G09C10329]
- United States Environmental Protection Agency [EPA STAR R83399001-0]
Rationale: To determine vascular signaling pathways involved in inhaled air pollution (vehicular engine emission) exposure-induced exacerbation of atherosclerosis that are associated with onset of clinical cardiovascular events. Objectives: To elucidate the role of oxidized low-density lipoprotein (oxLDL) and its primary receptor on endothelial cells, the lectin-like oxLDL receptor (LOX-1), in regulation of endothelin-1 expression and matrix metalloproteinase activity associated with inhalational exposure to vehicular engine emissions. Methods: Atherosclerotic apolipoprotein E knockout mice were exposed by inhalation to filtered air or mixed whole engine emissions (250 mu g particulate matter [PM]/m(3) diesel + 50 mu g PM/m(3) gasoline exhausts) 6 h/d for 7 days. Concurrently, mice were treated with either mouse IgG or neutralizing antibodies to LOX-1 every other day. Vascular and plasma markers of oxidative stress and expression proatherogenic factors were assessed. In a parallel study, healthy human subjects were exposed to either 100 mu g PM/m(3) diesel whole exhaust or high-efficiency particulate air and charcoal-filtered clean air (control subjects) for 2 hours, on separate occasions. Measurements and Main Results: Mixed emissions exposure increased oxLDL and vascular reactive oxygen species, as well as LOX-1, matrix metalloproteinase-9, and endothelin-1 mRNA expression and also monocyte/macrophage infiltration, each of which was attenuated with LOX-1 antibody treatment. In a parallel study, diesel exhaust exposure in volunteer human subjects induced significant increases in plasma-soluble LOX-1. Conclusions: These findings demonstrate that acute exposure to vehicular source pollutants results in up-regulation of vascular factors associated with progression of atherosclerosis, endothelin-1, and matrix metalloproteinase-9, mediated through oxLDL-LOX-1 receptor signaling, which may serve as a novel target for future therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据