Effects of nicotine, its metabolites and tobacco extracts on human platelet function in vitro

Ljungberg, Liza U.; Persson, Karin; Eriksson, Anna; Gréen, Henrik; Whiss, Per A

doi:10.1016/j.tiv.2013.01.004

Cited by 23 publications

(16 citation statements)

References 48 publications

(54 reference statements)

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“…While cigarette smoke in general leads to increased platelet activation [13][14][15][16][17][18], nicotine itself was reported to have protective effects in platelet function [23][24][25][26]. This inconsistency is probably attributed to the exceptional characteristics of nicotine itself [33] and the inability to separate the effect of nicotine from those of additional tobacco ingredients [34]. In our study, we could not confirm the reported differences in platelet degranulation, fibrinogen receptor activation and platelet aggregation between the smokers and nonsmokers.…”

Section: Discussioncontrasting

confidence: 77%

Megakaryocytes and platelets express nicotinic acetylcholine receptors but nicotine does not affect megakaryopoiesis or platelet function

Schedel¹,

Kaiser²,

Uhlig³

et al. 2015

Platelets

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In our previous investigations we have shown that platelets and their precursors express nicotinic α7 acetylcholine receptors (nAChRα7) that are involved in platelet function and in vitro differentiation of the megakaryoblastic cell line MEG-01. In this study, we were interested in the expression analysis of additional nAChR and the effects of nicotine in an ex vivo model using megakaryocytic cells differentiated from cord blood derived CD34(+) cells (CBMK) and an in vivo model using blood samples from smokers. CBMK were differentiated with thrombopoietin (TPO) for up to 17 days. Quantitative real-time PCR (QRT-PCR), Western blot analysis and flow cytometry were used to investigate nAChR expression (nAChRα7, nAChRα4, nAChRβ2) and nicotine effects. In blood samples of 15 nonsmokers and 16 smokers platelet parameters (count, mean platelet volume--MPV and platelet distribution width--PDW) were determined as indicators for changes of in vivo megakaryopoiesis. Platelet function was determined by the use of whole blood aggregometry and flow cytometry. The functional role of nAChR was evaluated using specific antagonists in aggregometry. CHRNA7, CHRNA4 and CHRNB2 gene transcripts and the corresponding proteins could be identified in CBMK during all stages of differentiation. Platelets contain nAChRα7 and nAChRβ2 but not nAChRα4. Nicotine had no effect on TPO-induced differentiation of CBMK. There was no significant difference in all platelet parameters of the smokers compared to the nonsmokers. In line with this, cholinergic gene transcripts as well as the encoded proteins were equally expressed in both the study groups. Despite our observation of nAChR expression in megakaryopoiesis and platelets, we were not able to detect effects of nicotine in our ex vivo and in vivo models. Thus, the functional role of the nAChR in these cells remains open.

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Section: Discussioncontrasting

confidence: 77%

Megakaryocytes and platelets express nicotinic acetylcholine receptors but nicotine does not affect megakaryopoiesis or platelet function

Schedel¹,

Kaiser²,

Uhlig³

et al. 2015

Platelets

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show abstract

“…Ljungberg et al performed nicotine infusion studies to assess nicotine metabolism on platelet activity. 75 Their findings support in vitro studies performed by our group (unpublished data), demonstrating that nicotine and some metabolites do not overtly activate platelets. However, they found that nicotine exposure marginally inhibited platelet attachment to extracellular matrix (ECM) components, such as collagen.…”

Section: Platelets Nicotine and Tobaccosupporting

confidence: 82%

In VitroandEx VivoApproaches to Evaluate Next-Generation Tobacco and Non-Tobacco Products on Human Blood Platelets

Spinelli

Lannan

Loelius

et al. 2017

Applied In Vitro Toxicology

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Human blood platelets are major hemostatic regulators in the circulation and important in the mediation of chronic inflammation and immunomodulation. They are key elements that promote cardiovascular pathogenesis that leads to atherosclerosis, thrombosis, myocardial infarction, and stroke. New information on tobacco use and platelet dysregulation shows that these highly understudied vascular cells are dysregulated by tobacco smoke. Thus, platelet function studies should be an important consideration for the evaluation of existing and next-generation tobacco and non-tobacco products. Novel in vitro approaches are being sought to investigate these products and their influence on platelet function. Platelets are ideally suited for product assessment, as robust and novel in vitro translational methods are available to assess platelet function. Furthermore, the use of human biological systems has the advantage that risk predictions will better reflect the human condition.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Qasim

Karim

Silva‐Espinoza

et al. 2018

JAHA

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BackgroundCardiovascular disease is the main cause of death in the United States, with smoking being the primary preventable cause of premature death, and thrombosis being the main mechanism of cardiovascular mortality in smokers. Due to the perception that electronic/e‐cigarettes are “safer/less harmful” than conventional cigarettes, their usage—among a variety of ages—has increased tremendously during the past decade. Notably, there are limited studies regarding the negative effects of e‐cigarettes on the cardiovascular system, which is also the subject of significant debate.Methods and ResultsWe employed a passive e‐VapeTM vapor inhalation system and developed an in vivo whole‐body e‐cigarette mouse exposure protocol that mimics real‐life human exposure scenarios/conditions and investigated the effects of e‐cigarettes and clean air on platelet function and thrombogenesis. Our results show that platelets from e‐cigarette–exposed mice are hyperactive, with enhanced aggregation, dense and α granule secretion, activation of the αIIbβ3 integrin, phosphatidylserine expression, and Akt and ERK activation, when compared with clean air–exposed platelets. E‐cigarette–exposed platelets were also found to be resistant to inhibition by prostacyclin, relative to clean air. Furthermore, the e‐cigarette–exposed mice exhibited a shortened thrombosis occlusion and bleeding times.ConclusionsTaken together, our data demonstrate for the first time that e‐cigarettes alter physiological hemostasis and increase the risk of thrombogenic events. This is attributable, at least in part, to the hyperactive state of platelets. Thus, the negative health consequences of e‐cigarette exposure should not be underestimated and warrant further investigation.

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Effects of nicotine, its metabolites and tobacco extracts on human platelet function in vitro

Cited by 23 publications

References 48 publications

Megakaryocytes and platelets express nicotinic acetylcholine receptors but nicotine does not affect megakaryopoiesis or platelet function

Megakaryocytes and platelets express nicotinic acetylcholine receptors but nicotine does not affect megakaryopoiesis or platelet function

In VitroandEx VivoApproaches to Evaluate Next-Generation Tobacco and Non-Tobacco Products on Human Blood Platelets

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

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