OBJECTIVE Cardiovascular disease is a major public health problem. Among cardiovascular disease's risk factors, tobacco smoking is considered the single most preventable cause of death, with thrombosis being the main mechanism of cardiovascular disease mortality in smokers. While tobacco smoking has been on the decline, the use of waterpipes/hookah has been rising, mainly due to the perception that they are less harmful than regular cigarettes. Strikingly, there are few studies on the negative effects of waterpipes on the cardiovascular system, and none regarding their direct contribution to thrombus formation. Approach and Results: We used a waterpipe whole-body exposure protocol that mimics real-life human exposure scenarios and investigated its effects, relative to clean air, on platelet function, hemostasis, and thrombogenesis. We found that waterpipe smoke (WPS)-exposed mice exhibited both shortened thrombus occlusion and bleeding times. Further, our results show that platelets from WPS-exposed mice are hyperactive, with enhanced agonist-induced aggregation, dense and α-granule secretion, αIIbβ3 integrin activation, phosphatidylserine expression, and platelet spreading, when compared with clean air-exposed platelets. Finally, at the molecular level, it was found that Akt (protein kinase B) and ERK (extracellular signal-regulated kinases) phosphorylation are enhanced in the WPS and in nicotine-treated platelets. CONCLUSIONS Our findings demonstrate that WPS exposure directly modulates hemostasis and increases the risk of thrombosis and that this is mediated, in part, via a state of platelet hyperactivity. The negative health impact of WPS/hookah, therefore, should not be underestimated. Moreover, this study should also help in raising public awareness of the toxic effects of waterpipe/hookah.

中文翻译：

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短期暴露于水烟/水烟烟雾中会触发血小板过度活跃状态，并增加血栓形成的风险。

目的心血管疾病是主要的公共卫生问题。在心血管疾病的危险因素中，吸烟被认为是最可预防的死亡原因，而血栓形成是吸烟者心血管疾病死亡的主要机制。尽管吸烟一直在减少，但使用水烟斗/烟叶的人数一直在增加，这主要是因为人们认为烟斗的危害性不如普通香烟。引人注目的是，关于水管对心血管系统的负面影响的研究很少，也没有关于水管对血栓形成的直接贡献的研究。方法和结果：我们使用了水管全身暴露方案，该方案模仿了现实生活中的人类暴露场景，并研究了其相对于清洁空气对血小板功能，止血和血栓形成的影响。我们发现，暴露于水烟的小鼠表现出较短的血栓闭塞和出血时间。此外，我们的研究结果表明，与清洁空气暴露的血小板相比，暴露于WPS的小鼠的血小板活动过度，激动剂诱导的聚集增强，致密和α颗粒分泌，αIIbβ3整联蛋白激活，磷脂酰丝氨酸表达和血小板扩散。最后，在分子水平上，发现WPS和尼古丁处理过的血小板中Akt（蛋白激酶B）和ERK（细胞外信号调节激酶）的磷酸化增强。结论我们的发现表明，WPS暴露直接调节止血作用并增加了血栓形成的风险，并且这部分是通过血小板多动状态来介导的。因此，WPS / hookah对健康的负面影响，不容小under。此外，这项研究还应有助于提高公众对水烟/胡麻的毒性作用的认识。