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; Yuchuan Ding

doi:10.18632/oncotarget.23347

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

Oncotarget. 2017 Dec 16;9(3):3765-3778. doi: 10.18632/oncotarget.23347. eCollection 2018 Jan 9.

Authors

Longfei Guan^{1

2}, Xiaokun Geng^{1

2

3}, Jiamei Shen^{1

2}, James Yip², Fengwu Li¹, Huishan Du^{1

3}, Zhili Ji⁴, Yuchuan Ding^{1

2}

Affiliations

¹ China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China.
² Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan, USA.
³ Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China.
⁴ Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China.

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.

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