Endothelial dysfunction represents the initial stage in atherosclerotic lesion development which occurs physiologically during aging, but external factors like diet, sedentary lifestyle, smoking accelerate it. Since cigarette smoking promotes oxidative stress and cell damage, we developed an in vitro model of endothelial dysfunction using vascular cells exposed to chemicals present in cigarette smoke, to help elucidate the protective effects of anti-inflammatory and antioxidant agents, such as ubiquinol and vitamin K, that play a fundamental role in vascular health. Treatment of both young and senescent Human Umbilical Vein Endothelial Cells (HUVECs) for 24 h with cigarette smoke extract (CSE) decreased cellular viability, induced apoptosis via reactive oxygen species (ROS) imbalance and mitochondrial dysfunction and promoted an inflammatory response. Moreover, the senescence marker SA-β-galactosidase was observed in both young CSE-exposed and in senescent HUVECs suggesting that CSE exposure accelerates aging in endothelial cells. Supplementation with 10 µM ubiquinol and menaquinone-7 (MK7) counteracted oxidative stress and inflammation, resulting in improved viability, decreased apoptosis and reduced SA-β-galactosidase, but were ineffective against CSE-induced mitochondrial permeability transition pore opening. Other K vitamins tested like menaquinone-4 (MK4) and menaquinone-1 (K1) were less protective. In conclusion, CSE exposure was able to promote a stress-induced senescent phenotype in young endothelial cells likely contributing to endothelial dysfunction in vivo. Furthermore, the molecular changes encountered could be offset by ubiquinol and menaquinone-7 supplementation, the latter resulting the most bioactive K vitamin in counteracting CSE-induced damage.

中文翻译：

---

生物活性醌在暴露于香烟烟雾提取物的内皮细胞应激诱导的衰老表型中的保护作用。

内皮功能障碍代表动脉粥样硬化病变发展的初始阶段，该阶段在衰老过程中在生理上发生，但是诸如饮食，久坐的生活方式，吸烟等外部因素加速了它的发展。由于吸烟会促进氧化应激和细胞损伤，因此我们利用暴露于香烟烟雾中化学物质的血管细胞建立了内皮功能障碍的体外模型，以帮助阐明抗炎剂和抗氧化剂（如泛醇和维生素K）的保护作用，在血管健康中起着根本性的作用。香烟烟雾提取物（CSE）治疗年轻和衰老的人脐静脉内皮细胞（HUVEC）24小时，降低了细胞活力，通过活性氧（ROS）失衡和线粒体功能障碍诱导凋亡，并促进炎症反应。此外，在年轻的CSE暴露者和衰老的HUVECs中均观察到衰老标记SA-β-半乳糖苷酶，表明CSE暴露加速了内皮细胞的衰老。补充10 µM泛醇和甲萘醌7（MK7）可抵消氧化应激和炎症，从而提高生存力，减少细胞凋亡并减少SA-β-半乳糖苷酶，但对CSE诱导的线粒体通透性转变孔开放无效。测试的其他K维生素（如甲萘醌4（MK4）和甲萘醌1（K1））的保护作用较小。结论，CSE暴露能够在年轻的内皮细胞中促进应激诱导的衰老表型，可能在体内导致内皮功能障碍。此外，所遇到的分子变化可通过补充泛醇和甲萘醌7来抵消，甲萘醌7补充剂在抵抗CSE诱导的损害中产生了最具生物活性的K维生素。