Exposure to acrolein by inhalation causes platelet activation

Abstract

Acrolein is a common air pollutant that is present in high concentrations in wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and emissions. Exposure to acrolein containing environmental pollutants such as tobacco smoke and automobile exhaust has been linked to the activation of the coagulation and hemostasis pathways and thereby to the predisposition of thrombotic events in human. To examine the effects of acrolein on platelets, adult male C57Bl/6 mice were subjected acute (5 ppm for 6 h) or sub-chronic (1 ppm, 6h/day for 4 days) acrolein inhalation exposures. The acute exposure to acrolein did not cause pulmonary inflammation and oxidative stress, dyslipidemia or induce liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were comparable to controls, but acrolein-exposure increased the abundance of protein-acrolein adducts in platelets. Platelets isolated from mice, exposed to both acute and sub-chronic acrolein levels, showed increased ADP-induced platelet aggregation. Exposure to acrolein also led to an increase in the indices of platelet activation such as the formation of platelet-leukocyte aggregates in the blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding time was decreased in acrolein exposed mice. Plasma levels of PF4 were also increased in mice exposed to environmental tobacco smoke. Similar to inhalation exposure, acrolein feeding to mice also increased platelet activation and established a pro-thrombotic state in mice. Together, our data suggest that acrolein is an important contributing factor to the pro-thrombotic risk in human exposure to pollutants such as tobacco smoke or automobile exhaust, or through dietary consumption.

Cigarette Smoke Component Acrolein Modulates Chromatin Assembly by Inhibiting Histone Acetylation

“…However, in human lung cells, Acr exposure degraded some DNA repair proteins, such as XPA, XPC, hOGG1, PMS2, and MLH1 proteins, but had no effect on MSH2 and Ref1 (21), suggesting that there is protein specificity for Acr reactivity by as yet unknown mechanisms. Consistent with these reports, the lungs of mice after Acr exposure showed increased Acr-lysine adduction in several but not all proteins (46). We showed here that Acr preferentially reacts with unmodified free histones rather than with already modified nucleosomal histones (Fig.…”

Short‐Term E‐Cigarette Exposure Increases the Risk of Thrombogenesis and Enhances Platelet Function in Mice

“…This finding is not surprising given the “thrombosis” phenotype we observed and is supported by previous studies by us and others, in which exposure to tobacco and its constituents was found to reduce the tail bleeding time 38, 93. Of note, our data revealed that e‐cigarettes do not modulate/reduce platelet count, at least under short‐term exposure conditions.…”

“…It is noteworthy that exposure to some of these toxicants, albeit from traditional tobacco smoking and other sources, was found to be associated with an enhanced platelet activation phenotype 6. Furthermore, while the effects of nicotine on platelet activation/aggregation are still controversial,16, 105, 106, 107, 108 particulate matter109, 110 and acrolein93 were indeed found to enhance platelet function.…”

Augmented atherogenesis in ApoE-null mice co-exposed to polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin

“…PF4 is synthesized in megakaryocytes and stored in α-granules. PF4 released from activated platelets binds to heparin-like molecules and facilitates thrombus formation at the site of injury (Sithu et al, 2010). PF4 has been shown to enhance the accumulation of lipoproteins in vascular cells and augments the binding of oxLDL to endothelial cells, smooth muscle cells and macrophages.…”