Oncotarget

Research Papers:

PM2.5 inhalation induces intracranial atherosclerosis which may be ameliorated by omega 3 fatty acids

Longfei Guan, Xiaokun Geng _, Jiamei Shen, James Yip, Fengwu Li, Huishan Du, Zhili Ji and Yuchuan Ding

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Oncotarget. 2018; 9:3765-3778. https://doi.org/10.18632/oncotarget.23347

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Abstract

Longfei Guan1,2, Xiaokun Geng1,2,3, Jiamei Shen1,2, James Yip2, Fengwu Li1, Huishan Du1,3, Zhili Ji4 and Yuchuan Ding1,2

1China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China

2Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan, USA

3Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China

4Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China

Correspondence to:

Xiaokun Geng, email: [email protected]

Yuchuan Ding, email: [email protected]

Keywords: high-cholesterol diet (HCD); NG-nitro-L-arginine methyl ester (L-NAME); brain; inflammation; air pollution

Received: October 05, 2017     Accepted: November 26, 2017     Published: December 16, 2017

ABSTRACT

Background: Intracranial atherosclerosis (ICA) a major health problem. This study investigated whether inhalation of fine airborne particulate matters (PM2.5) causes ICA and whether omega-3 fatty acids (O3FA) attenuated the development of ICA.

Results: Twelve but not 6 week exposure significantly increased triglycerides (TG) in normal chow diet (NCD), while PM2.5 enhanced all lipid profiles (TG, low density lipoprotein (LDL) and cholesterol (CHO)) after both 6 and 12-week exposure with high-cholesterol diet (HCD). PM2.5 exposure for 12 but not 6 weeks significantly induced middle cerebral artery (MCA) narrowing and thickening, in association with the enhanced expression of inflammatory cytokines, (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interferon gamma (IFN-γ)), vascular cell adhesion molecule 1 (VCAM-1) and inducible nitric oxide synthase (iNOS). O3FA significantly attenuated vascular alterations, even without favorable changes in lipid profiles, in association with reduced expression of IL-6, TNF-α, MCP-1, IFN-γ, VCAM-1 and iNOS in brain vessels.

Conclusions: PM2.5 exposure for 12 weeks aggravates ICA in a dietary model (HCD + short-term L-NAME), which may be mediated by vascular inflammation. O3FA dietary supplementation prevents ICA development and inflammatory reaction in cerebral vessels.

Methods: Adult Sprague-Dawly rats were under filtered air (FA) or PM2.5 exposure with NCD or HCD for 6 or 12 weeks. Half of the HCD rats were treated with O3FA (5 mg/kg/day) by gavage. A total of 600 mg NG-nitro-L-arginine methyl ester (L-NAME, 3 mg/mL) per rat was administered over two weeks as supplementation in the HCD group. Blood lipids, including LDL, CHO, TG and high density lipoprotein (HDL), were measured at 6 and 12 weeks. ICA was determined by lumen diameter and thickness of the MCA. Inflammatory markers, IL-6, TNF-α, MCP-1, IFN-γ, VCAM-1 and iNOS were assessed by real-time PCR for mRNA and Western blot for protein expression.


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