Pro-thrombotic changes associated with exposure to ambient ultrafine particles in patients with chronic obstructive pulmonary disease: roles of lipid peroxidation and systemic inflammation

Abstract

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-α], 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 103/cm3 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 103/cm3 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-1α, MIP-1β, TNF-α, and IL-1β 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 registrationChiCTR1900023692. Date of registration June 7, 2019, i.e. retrospectively registered.

Particulate Air Pollution and Blood Pressure: Signaling by the Arachidonate Metabolism

“…We observed associations between short-term exposure to PM 2.5 , BC, and Acc and the serum concentrations of ARA and eicosanoids, supporting our reports that shortterm PM exposure is associated with ARA metabolism in healthy adults and susceptible populations. [14][15][16]33 In vitro, exposure to PM induced the production of eicosanoids in epithelial cells, 34 alveolar macrophages, 35 and endothelial cells. 36 Exposure to PM altered the levels of eicosanoids in mouse blood, 37 lung, 38 and small intestine.…”

“…Short-term exposure to ambient air PM is associated with circulating levels of ARA and eicosanoids derived from the cyclooxygenase, lipoxygenase, and CYP pathways in humans. [14][15][16] However, studies assessing the signaling roles of ARA metabolism in PM-associated hemodynamic changes are lacking. Herein, we assessed the associations of short-term exposure to PM, namely fine particulate matter (PM 2.5 ), black carbon (BC), accumulation mode particles (Acc), and ultrafine particles (UFPs), with brachial and central BP, arterial stiffness, and cardiac and endothelial function.…”

The Effects and Pathogenesis of PM2.5 and Its Components on Chronic Obstructive Pulmonary Disease

“…142 In COPD patients, exposure to ambient ultrafine particles was also linked to higher levels of IL-8, MCP-1, MIP-1α, MIP-1β, TNF-α, and IL-1β. 143 There is also evidence that PM2.5 can release pro-inflammatory compounds into the blood circulation, resulting in systemic inflammation, which is indicated by white blood cells (WBC), C-reactive protein (CRP) and serum cytokine levels. 144 This further contributes to the progression of COPD and its incidence.…”

Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures

“…Inflammation is another critical mechanism affected by these pollutants [10,155,[175][176][177][178][179][180][181][182][183][184][185][186]. Chronic exposure to pollutants can trigger a sustained inflammatory response within the cardiovascular system and other organs as well.…”