Platelet-Derived Nitric Oxide Signaling and Regulation

Gkaliagkousi, Εugenia; Ritter, James M.; Ferro, Albert

doi:10.1161/circresaha.107.158410

Cited by 134 publications

(109 citation statements)

References 132 publications

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“…After “validating” our model, we first sought to investigate the impact of e‐cigarettes on thrombogenesis, as it is the major cause of tobacco‐induced CVD,38 including thrombosis‐based diseases 17, 77, 78, 79, 80, 81, 82, 83. Our findings revealed, for the first time, a drastic reduction in the time for carotid artery occlusion, indicating a prothrombotic phenotype, even after only a week of whole‐body exposure to e‐cigarettes.…”

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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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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“…Nitric oxide acts as an essential molecule in the regulation of PLT function [38]. There are two NO synthase (NOS) insoforms in PLTs; iNOS and eNOS.…”

Section: Effects Of Nos and Ros Endproductsmentioning

confidence: 99%

Platelet Aggregation Increased by Advanced Glycated Hemoglobin

M¹

2015

J Blood Disord Transfus

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“…Impaired endothelial function, decreased eNOS activity, and/or NO bioavailability are conditions strongly related to cardiovascular disease. 26,46 Thus, a systemic eNOS deficiency and/or dysfunction appears to prevail in patients with cardiovascular disease the consequences of which are not limited to impaired vascular function, but may also affect function of platelets 47 and red blood cells.…”

Section: Is Red Cell Enos Of Relevance To Cardiovascular Disease?mentioning

confidence: 99%

Human red blood cells at work: identification and visualization of erythrocytic eNOS activity in health and disease

Cortese‐Krott

Rodriguez-Mateos

Sansone

et al. 2012

Blood

154

120

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IntroductionThe key event in the pathogenesis of arteriosclerosis is believed to be a dysfunction of the endothelium with disruption of vascular homeostasis, predisposing blood vessels to vasoconstriction, inflammation, leukocyte adhesion, thrombosis, and proliferation of vascular smooth muscle cells. Red blood cells (RBCs) are typically considered as shuttles of respiratory gases and nutrients for tissues, less so compartments important to vascular integrity. Patients with coronary artery disease (CAD) and concomitant anemia have a poorer prognosis after myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting, and are more prone to developing heart failure with fatal outcomes. [1][2][3] Surprisingly, erythropoietin treatment fails to improve diagnosis, indicating that a compromised gas exchange/nutrient transport capacity of blood is insufficient to explain this outcome.Nitric oxide (NO) is an essential short-lived signaling/ regulatory product of a healthy endothelium that is critically important for vascular health. Decreased production and/or bioactivity of NO are a hallmark of endothelial dysfunction and have been shown to contribute to accelerated atherogenesis. In the cardiovascular system, NO is continuously produced in endothelial cells (ECs) by the type III isoform of NO synthase (eNOS, NOS3; EC 1.14.13.39). 4 In addition to endothelial cells, some circulating blood cells also contain eNOS.It is an accepted dogma that RBCs take up and inactivate endothelium-derived NO via rapid reaction with oxyhemoglobin to form methemoglobin and nitrate, thereby limiting NO available for vasodilatation. Yet it has also been shown that RBCs not only act as "NO sinks" but synthesize, store, and transport NO metabolic products. Under hypoxic conditions in particular, it has been demonstrated that RBCs induce NO-dependent vasorelaxation. 5,6 Mechanisms of release and potential sources of NO in RBCs are still a matter of debate, but candidates include iron-nitrosylhemoglobin, 7 S-nitrosohemoglobin, [8][9][10] and nitrite. The latter may form NO either via deoxyhemoglobin 5,11 or xanthine oxidoreductase (XOR)-mediated reduction, 6,12 or via spontaneous 12 and carbonic anhydrase-facilitated disproportionation. 13 Most of these processes show a clear oxygen-dependence, and several are favored by low oxygen tensions. The relative contribution of either mechanism to NO formation varies with oxygen partial pressure along the vascular tree. In addition, RBCs release ATP when subjected to hypoxia, providing an alternative vasodilatory pathway. 14 The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. 16,19 and citrulline 15,18 in the supernatant. However, Kang et al failed to measure citrulline production in RBC lysates, 20 maybe because of loss of cellular structures or cofactors important for activity. 21 Another recent study fai...

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Platelet-Derived Nitric Oxide Signaling and Regulation

Cited by 134 publications

References 132 publications

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

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

Platelet Aggregation Increased by Advanced Glycated Hemoglobin

Human red blood cells at work: identification and visualization of erythrocytic eNOS activity in health and disease

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