Pro-thrombotic effect of exercise in a polluted environment: a P-selectin- and CD63-related platelet activation effect

Abstract

Exposure to diesel exhaust is an important cardiovascular risk factor and may promote atherothrombotic events. Some data suggest that polluted air exposure could affect haemostasis through platelet activation. The aim of the study was to investigate the effects of acute exposure to diesel exhaust on platelet activation and platelet function. We tested the hypothesis in a randomised, crossover study in 25 healthy men exposed to ambient and polluted air; 11 of the subjects also performed exercise during exposure sessions. Platelet activation was evaluated by surface expression of CD62P (P-selectin) and CD63 (dense granule glycoprotein) using flow cytometry of labelled platelets. Platelet function was measured using the PFA-100 platelet function analyser and by Multiplate whole blood impedance platelet aggregometry. Acute diesel exhaust exposure had no effect on platelet activation at rest, but exercise in polluted air increased the collagen-induced expression of CD62P and CD63 (both p< 0.05). The increase in the expression of CD62P and CD63 was related to the total amount of PM2.5 inhaled during the exercise sessions (r=+0.58 and +0.60, respectively, both p< 0.05). Platelet aggregation was not impaired after polluted air exposure at rest or during exercise. In conclusion, in healthy subjects, diesel exhaust exposure induces platelet activation as illustrated by a dose-response increase in the release of CD62P and CD63. This platelet priming effect could be a contributor to the triggering of atherothrombotic events related to air pollution exposure.

Left ventricular function in relation to chronic residential air pollution in a general population

“…In experimental studies systolic 50 , 51 and diastolic 51 function decreased in response to PM2.5 exposure. Human studies suggested that circulating adhesion molecules VCAM-1, 37 , 38 ICAM-1, 36 , 38 E-selectin 39 and P-selectin 52 reflect a systemic inflammatory state and play a role in mediating the adverse cardiovascular effects of air pollution, subsequently leading to coronary heart disease 36 or increased susceptibility to thrombotic complications. 52 The evidence from these experimental 50 , 51 and human 36 – 39 , 52 studies justified our path analysis, focusing on circulating adhesion molecules, measured at the time of echocardiography.…”

Endothelial inflammatory transcriptional responses to an altered plasma exposome following inhalation of diesel emissions

“…However, the return to T 0 gene expression levels at T 24 suggest that this cluster captures early changes in gene expression that restore to T 0 levels, at least by 24 hours. Although there was limited statistical enrichment for biological pathways within Cluster 2, genes such as BTNL are suggested to exacerbate asthma (Yamazaki, Goya et al 2010) and SELP expression/activity is a target for asthma therapy (Schumacher 2007, Takyar, Vasavada et al 2013) and associates with diesel exposure in other models (Wauters, Esmaeilzadeh et al 2015). Additional genes from Cluster 2 include F7 , a serum prothrombin conversion accelerator, that associates with enhanced disease risk associated with smoking (Redondo, Watzke et al 1999, Ben-Hadj-Khalifa, Lakhal et al 2013).…”

Acid Sphingomyelinase Deficiency Type B Patient-Derived Liver Organoids Reveals Altered Lysosomal Gene Expression and Lipid Homeostasis

“…In this study, lower levels of phospholipid involved in the coagulation process, phostatidylcholine (PC), a component of the platelet-activating factor, were detected in ASMD type B organoids, which could relate to the coagulation problems associated with the disease. Furthermore, a significant reduction in the expression of the CD63 gene, a marker of blood platelet activation [ 49 ], was found in the ASMD type B liver organoids. The lack of CD63 expression has also been described in patients with Hermansky–Pudlak syndrome (HPS), which has hemorrhages due to platelet deficiency, among other symptoms [ 50 ].…”