PMID- 36280873 OWN - NLM STAT- MEDLINE DCOM- 20221026 LR - 20230308 IS - 1743-8977 (Electronic) IS - 1743-8977 (Linking) VI - 19 IP - 1 DP - 2022 Oct 24 TI - Pro-thrombotic changes associated with exposure to ambient ultrafine particles in patients with chronic obstructive pulmonary disease: roles of lipid peroxidation and systemic inflammation. PG - 65 LID - 10.1186/s12989-022-00503-9 [doi] LID - 65 AB - BACKGROUND: Exposure to particulate matter air pollution is associated with an increased risk of cardiovascular mortality in patients with chronic obstructive pulmonary disease (COPD), but the underlying mechanisms are not yet understood. Enhanced platelet and pro-thrombotic activity in COPD patients may explain their increased cardiovascular risk. We aim to explore whether short-term exposure to ambient particulate matter is associated with pro-thrombotic changes in adults with and without COPD, and investigate the underlying biological mechanisms in a longitudinal panel study. Serum concentration of thromboxane (Tx)B2 was measured to reflect platelet and pro-thrombotic activity. Lipoxygenase-mediated lipid peroxidation products (hydroxyeicosatetraenoic acids [HETEs]) and inflammatory biomarkers (interleukins [ILs], monocyte chemoattractant protein-1 [MCP-1], tumour necrosis factor alpha [TNF-alpha], and macrophage inflammatory proteins [MIPs]) were measured as potential mediating determinants of particle-associated pro-thrombotic changes. RESULTS: 53 COPD and 82 non-COPD individuals were followed-up on a maximum of four visits conducted from August 2016 to September 2017 in Beijing, China. Compared to non-COPD individuals, the association between exposure to ambient ultrafine particles (UFPs) during the 3-8 days preceding clinical visits and the TxB2 serum concentration was significantly stronger in COPD patients. For example, a 10(3)/cm(3) increase in the 6-day average UFP level was associated with a 25.4% increase in the TxB2 level in the COPD group but only an 11.2% increase in the non-COPD group. The association in the COPD group remained robust after adjustment for the levels of fine particulate matter and gaseous pollutants. Compared to the non-COPD group, the COPD group also showed greater increases in the serum concentrations of 12-HETE (16.6% vs. 6.5%) and 15-HETE (9.3% vs. 4.5%) per 10(3)/cm(3) increase in the 6-day UFP average. The two lipid peroxidation products mediated 35% and 33% of the UFP-associated increase in the TxB2 level of COPD patients. UFP exposure was also associated with the increased levels of IL-8, MCP-1, MIP-1alpha, MIP-1beta, TNF-alpha, and IL-1beta in COPD patients, but these inflammatory biomarkers did not mediate the TxB2 increase. CONCLUSIONS: Short-term exposure to ambient UFPs was associated with a greater pro-thrombotic change among patients with COPD, at least partially driven by lipoxygenase-mediated pathways following exposure. Trial registration ChiCTR1900023692 . Date of registration June 7, 2019, i.e. retrospectively registered. CI - (c) 2022. The Author(s). FAU - Wang, Teng AU - Wang T AD - BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, China. FAU - Chen, Xi AU - Chen X AD - BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, China. AD - Hebei Technology Innovation Center of Human Settlement in Green Building (TCHS), Shenzhen Institute of Building Research Co., Ltd., Xiongan, China. FAU - Li, Haonan AU - Li H AD - BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, China. FAU - Chen, Wu AU - Chen W AD - BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, China. FAU - Xu, Yifan AU - Xu Y AD - BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, China. FAU - Yao, Yuan AU - Yao Y AD - BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, China. FAU - Zhang, Hanxiyue AU - Zhang H AD - BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, China. FAU - Han, Yiqun AU - Han Y AD - BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, China. AD - Environmental Research Group, MRC Centre for Environment and Health, Imperial College London, London, UK. FAU - Zhang, Lina AU - Zhang L AD - Shi Cha Hai Community Health Service Center, Beijing, China. FAU - Que, Chengli AU - Que C AD - Peking University First Hospital, Peking University, Beijing, China. FAU - Gong, Jicheng AU - Gong J AD - BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, China. FAU - Qiu, Xinghua AU - Qiu X AD - BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, China. FAU - Zhu, Tong AU - Zhu T AD - BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, China. tzhu@pku.edu.cn. LA - eng SI - ChiCTR/ChiCTR1900023692 GR - MR/S019669/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221024 PL - England TA - Part Fibre Toxicol JT - Particle and fibre toxicology JID - 101236354 RN - 0 (Particulate Matter) RN - 0 (Chemokine CCL2) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Air Pollutants) RN - 0 (Chemokine CCL3) RN - 0 (Chemokine CCL4) RN - 59985-28-3 (12-Hydroxy-5,8,10,14-eicosatetraenoic Acid) RN - 0 (Interleukin-8) RN - 0 (Biomarkers) RN - EC 1.13.11.- (Lipoxygenases) RN - 0 (Thromboxanes) SB - IM MH - Adult MH - Humans MH - Particulate Matter/toxicity MH - Chemokine CCL2 MH - Tumor Necrosis Factor-alpha MH - *Air Pollutants/toxicity/analysis MH - Lipid Peroxidation MH - Chemokine CCL3 MH - Chemokine CCL4 MH - 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid MH - Interleukin-8 MH - *Air Pollution MH - *Pulmonary Disease, Chronic Obstructive/chemically induced MH - Inflammation/chemically induced MH - Biomarkers MH - Lipoxygenases MH - Thromboxanes MH - Environmental Exposure/analysis PMC - PMC9590143 OTO - NOTNLM OT - COPD OT - Inflammation OT - Lipid peroxidation OT - Particulate matter OT - Platelet activation OT - Thrombosis OT - Ultrafine particles COIS- The authors declare that they have no competing interests. EDAT- 2022/10/26 06:00 MHDA- 2022/10/27 06:00 PMCR- 2022/10/24 CRDT- 2022/10/25 00:41 PHST- 2022/05/22 00:00 [received] PHST- 2022/09/08 00:00 [accepted] PHST- 2022/10/25 00:41 [entrez] PHST- 2022/10/26 06:00 [pubmed] PHST- 2022/10/27 06:00 [medline] PHST- 2022/10/24 00:00 [pmc-release] AID - 10.1186/s12989-022-00503-9 [pii] AID - 503 [pii] AID - 10.1186/s12989-022-00503-9 [doi] PST - epublish SO - Part Fibre Toxicol. 2022 Oct 24;19(1):65. doi: 10.1186/s12989-022-00503-9.