PMID- 29423081 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220314 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 9 IP - 3 DP - 2018 Jan 9 TI - PM2.5 inhalation induces intracranial atherosclerosis which may be ameliorated by omega 3 fatty acids. PG - 3765-3778 LID - 10.18632/oncotarget.23347 [doi] AB - 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-alpha), monocyte chemoattractant protein-1 (MCP-1), interferon gamma (IFN-gamma)), 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-alpha, MCP-1, IFN-gamma, 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-alpha, MCP-1, IFN-gamma, VCAM-1 and iNOS were assessed by real-time PCR for mRNA and Western blot for protein expression. FAU - Guan, Longfei AU - Guan L AD - China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China. AD - Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan, USA. FAU - Geng, Xiaokun AU - Geng X AD - China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China. AD - Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan, USA. AD - Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China. FAU - Shen, Jiamei AU - Shen J AD - China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China. AD - Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan, USA. FAU - Yip, James AU - Yip J AD - Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan, USA. FAU - Li, Fengwu AU - Li F AD - China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China. FAU - Du, Huishan AU - Du H AD - China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China. AD - Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China. FAU - Ji, Zhili AU - Ji Z AD - Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China. FAU - Ding, Yuchuan AU - Ding Y AD - China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Tongzhou Qu, China. AD - Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan, USA. LA - eng PT - Journal Article DEP - 20171216 PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 PMC - PMC5790498 OTO - NOTNLM OT - NG-nitro-L-arginine methyl ester (L-NAME) OT - air pollution OT - brain OT - high-cholesterol diet (HCD) OT - inflammation COIS- CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest. EDAT- 2018/02/10 06:00 MHDA- 2018/02/10 06:01 PMCR- 2018/01/09 CRDT- 2018/02/10 06:00 PHST- 2017/10/05 00:00 [received] PHST- 2017/11/26 00:00 [accepted] PHST- 2018/02/10 06:00 [entrez] PHST- 2018/02/10 06:00 [pubmed] PHST- 2018/02/10 06:01 [medline] PHST- 2018/01/09 00:00 [pmc-release] AID - 23347 [pii] AID - 10.18632/oncotarget.23347 [doi] PST - epublish SO - Oncotarget. 2017 Dec 16;9(3):3765-3778. doi: 10.18632/oncotarget.23347. eCollection 2018 Jan 9.