Comparative effects of inhaled diesel exhaust and ambient fine particles on inflammation, atherosclerosis, and vascular dysfunction

Abstract

Ambient air PM_2.5 (particulate matter less than 2.5 μm in diameter) has been associated with cardiovascular diseases (CVDs), but the underlying mechanisms affecting CVDs are unknown. The authors investigated whether subchronic inhalation of concentrated ambient PM_2.5 (CAPs), whole diesel exhaust (WDE), or diesel exhaust gases (DEGs) led to exacerbation of atherosclerosis, pulmonary and systemic inflammation, and vascular dysfunction; and whether DEG interactions with CAPs alter cardiovascular effects. ApoE^−/− mice were simultaneously exposed via inhalation for 5 hours/day, 4 days/week, for up to 5 months to one of five different exposure atmospheres: (1) filtered air (FA); (2) CAPs (105 μg/m³); (3) WDE (DEP = 436 μg/m³); (4) DEG (equivalent to gas levels in WDE group); and (5) CAPs+DEG (PM_2.5: 113 μg/m³; with DEG equivalent to WDE group). After 3 and 5 months, lung lavage fluid and blood sera were analyzed, and atherosclerotic plaques were quantified by ultrasound imaging, hematoxylin and eosin (H&E stain), and en face Sudan IV stain. Vascular functions were assessed after 5 months of exposure. The authors showed that (1) subchronic CAPs, WDE, and DEG inhalations increased serum vascular cell adhesion molecule (VCAM)-1 levels and enhanced phenylephrine (PE)-induced vasoconstriction; (2) for plaque exacerbation, CAPs > WDE > DEG = FA, thus PM components (not present in WDE) were responsible for plaque development; (3) atherosclerosis can exacerbated through mechanistic pathways other than inflammation and vascular dysfunction; and (4) although there were no significant interactions between CAPs and DEG on plaque exacerbation, it is less clear whether the effects of CAPs on vasomotor dysfunction and pulmonary/systemic inflammation were enhanced by the DEG coexposure.

Keywords::

• Air pollution
• atherosclerosis
• concentrated ambient PM2.5 (CAPs)
• diesel exhaust gases (DEGs)
• vascular dysfunction
• whole diesel exhaust (WDE)

Acknowledgments

We acknowledge technical assistance from Ximei Jin, Aixia Wang, Zhekang Yin, Martin Blaustein, and Mianhua Zhong.

Declaration of interest

Support for this study was from a center grant (ES 00260) and a research grant (ES015495) from the NIEHS; and from a research grant from the Health Effects Institute. Qinghua Sun was supported by a NIH grant (ES016588).