In Utero Third-Hand Smoke Impact on Platelet Function and Thrombogenesis

子宫内三手烟对血小板功能和血栓形成的影响

• 批准号: 10169638
• 负责人: Fadi T Khasawneh
• 金额: $ 18.92万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-22 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10169638
• 关键词: Address; Adult; Agonist; Air; Animal Diseases; Animal Model; Awareness; Biology; Blood Cells; Blood Coagulation Factor; Blood Platelets; C-reactive protein; Cardiovascular system; Child; DNA Methylation; Data; Development; Disease; Dose; Elements; Epigenetic Process; Epoprostenol; Exposure to; Foundations; Gender; Generations; Goals; Hand; Health; Hemostatic function; Hispanic Americans; Human; Immune system; Impaired wound healing; Inflammatory; Isoprostanes; Leukocytes; Long-Term Effects; Mediating; Mediator of activation protein; MicroRNAs; Minority; Mitochondria; Mitotic; Mus; Myocardial Infarction; Nature; Newborn Infant; Pathogenesis; Phenotype; Physiological; Platelet Activation; Platelet Count measurement; Platelet aggregation; Play; Policies; Prevention; Process; Public Health; Publishing; Reporting; Risk; Role; Shapes; Smoke; Smoking; Societies; Stimulus; Therapeutic; Thrombosis; Thromboxane A2; Time; Tobacco; Tobacco use; VWF gene; Vulnerable Populations; base; cardiovascular disorder risk; cardiovascular health; clinically relevant; cytokine; developmental plasticity; environmental tobacco smoke; epidemiology study; evidence base; experimental study; exposed human population; exposure route; extracellular; in utero; monocyte; neutrophil; offspring; platelet function; prenatal exposure; receptor; response; thirdhand smoke; thrombogenesis; tobacco control; toxicant; virtual

While the involvement of in utero exposure to first-hand smoke (FHS) and second-hand smoke (SHS) in the pathogenesis of thrombotic diseases is well documented, the contribution of the newly “discovered” third-hand form (THS) in such disease processes remains unknown. This derives, in part, from: (1) initial lack of knowedlge of THS existence; (2) lack of appreciation for its “real” negative health consequences; (3) lack of a THS-exosure animal model that mimics real-world scenarios; and (4) lack of studies regarding such consequences on platelet biology. The present application proposes experiments that address fundamental, mechanistic, epigenetic and clinically-relevant translational aspects of the adverse-health effects of the newly “realized” form of smoking, THS, in utero and in the context of thrombotic disease and platelet biology, and gender. Studies are also proposed to investigate, in a similar fashion, the toxicants that underlie THS effects on platelets and associated diseases. These studies are of paramount significance given that the dangers of THS are underestimated/unappreciated, despite evidence that it is more toxic than SHS, especially in vulnerable populations such as children and minorities (e.g., Hispanic Americans). The Aims of our proposal are: Aim 1. Investigate the impact of in utero THS-exposure on platelet-dependent diseases. While in utero exposure to the well-known FHS and SHS was found to contribute to the genesis of myocardial infarctions, whether in utero exposure to THS is also associated with an increased risk of thrombotic disorders, is yet to be determined. To address this issue, we will determine the ramifications of in utero THS exposure on normal hemostasis, platelet counts, as well as on clotting factors and other thrombosis mediators, in a dose-, and time- dependent fashion. Subsequent studies will examine whether in utero THS participates in the development of thrombotic disorders. Aim 2. Investigate the mechanism by which in utero THS-exposure modulates platelet function. Our recently published findings show, for the first time, that adult THS exposure modulates physiological hemostasis, and increases the risk of thrombogenesis, via enhancing platelet activation. However, whether in utero THS is associated with similar effects, and if so, the mechanism by which it modulates platelet function remain to be investigated. Thus, the overall goal of the experiments proposed in this section is to determine the significance, toxicants and mechanism of the impact of in utero THS-exposure on various platelet functional responses, platelet epigenetics, its effect on other blood cells (e.g., leukocytes) and thrombosis “markers”, as well as its major route of exposure. Collectively, these experiments will make significant contributions to our understanding of the consequences of in utero THS exposure on platelet activation and cardiovascular human health, its epigenetics, and the mechanism and toxicants by which THS exerts its effects.

而在子宫内接触一手烟（FHS）和二手烟（SHS）所涉及的

项目成果

In utero thirdhand smoke exposure modulates platelet function in a sex-dependent manner.

• DOI: 10.3324/haematol.2021.279388
• 发表时间: 2022-01-01
• 期刊: Haematologica
• 影响因子: 10.1
• 作者: Ali HEA;Alarabi AB;Karim ZA;Rodriguez V;Hernandez KR;Lozano PA;El-Halawany MS;Alshbool FZ;Khasawneh FT
• 通讯作者: Khasawneh FT

Exposure of Mice to Thirdhand Smoke Modulates In Vitro and In Vivo Platelet Responses.

• DOI: 10.3390/ijms23105595
• 发表时间: 2022-05-17
• 期刊: International journal of molecular sciences
• 影响因子: 5.6

Predicting thrombotic cardiovascular outcomes induced by waterpipe-associated chemicals using comparative toxicogenomic database: Genes, phenotypes, and pathways.

• DOI: 10.1016/j.lfs.2023.121694
• 发表时间: 2023-06-15
• 期刊: LIFE SCIENCES
• 影响因子: 6.1
• 作者: Alarabi, Ahmed B.;Mohsen, Attayab;Ben Taleb, Ziyad;Mizuguchi, Kenji;Alshbool, Fatima Z.;Khasawneh, Fadi T.
• 通讯作者: Khasawneh, Fadi T.

The JUUL E-Cigarette Elevates the Risk of Thrombosis and Potentiates Platelet Activation.

• DOI: 10.1177/1074248420941681
• 发表时间: 2020-11
• 期刊: Journal of cardiovascular pharmacology and therapeutics
• 影响因子: 2.6
• 作者: Ramirez JEM;Karim ZA;Alarabi AB;Hernandez KR;Taleb ZB;Rivera JO;Khasawneh FT;Alshbool FZ
• 通讯作者: Alshbool FZ

In Utero Thirdhand Smoke Modulates Platelet Gene Expression in Exposed Mice.

子宫内三手烟调节暴露小鼠的血小板基因表达。

• 发表时间: 2022
• 期刊: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
• 作者: Alarabi,AhmedB;Ali,HamdyE;Lozano,PatriciaA;Rodrigues,LeticiaA;Halawany,MedhatS;Alshbool,FatimaZ;Khasawneh,FadiT
• 通讯作者: Khasawneh,FadiT