AIMS Apelin and vitamin E have been proposed as signaling molecules, but their synergistic role is unknown. The aim of this work was to develop vitamin E TPGS/Apelin system to test their cardioprotective and metabolic efficacy in vitro and in vivo. METHODS FDA-approved surfactant D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-1000) and Apelin complex were characterized by physico-chemical methods (CMC determination, dynamic light scattering and circular dichroism). In vitro studies were carried out on H9C2 cardiomyoblasts and isolated murine cardiomyocytes. In vivo studies were performed in isoproterenol- and high-fat diet-induced cardiac remodeling models in mice. RESULTS We found that vitamin E TPGS/Apelin provide cardioprotective and metabolic efficacy in vitro and in vivo. In vitro studies revealed that vitamin E TPGS/Apelin reduces hypoxia-induced mitochondrial ROS production in cultured cardiomyocytes and H9C2 cardiomyoblasts. In addition, vitamin E TPGS/Apelin confers apoptotic response to hypoxic stress in cells. In a mouse model of isoproterenol-induced cardiac injury, TPGS is not able to affect cardiac remodeling, however combination of vitamin E TPGS and Apelin counteracts myocardial apoptosis, oxidative stress, hypertrophy and fibrosis. Furthermore, combination treatment attenuated obesity-induced cardiometabolic and fibrotic remodeling in mice. CONCLUSION Together, our data demonstrated the therapeutic benefits of vitamin E TPGS/Apelin complex to combat cardiovascular and metabolic disorders.

中文翻译：

---

维生素E TPGS / Apelin的体外和体内心脏保护和代谢功效。

AIMS Apelin和维生素E已被提议作为信号分子，但它们的协同作用尚不清楚。这项工作的目的是开发维生素E TPGS / Apelin系统，以在体外和体内测试其心脏保护和代谢功效。方法用理化方法（CMC测定，动态光散射和圆二色性）对FDA批准的表面活性剂D-α-生育酚聚乙二醇1000琥珀酸酯（TPGS-1000）和Apelin配合物进行表征。在H9C2心肌母细胞和分离的鼠心肌细胞上进行了体外研究。在小鼠体内由异丙肾上腺素和高脂饮食诱导的心脏重塑模型中进行了体内研究。结果我们发现维生素E TPGS / Apelin在体外和体内均可提供心脏保护和代谢功效。体外研究表明，维生素E TPGS / Apelin可以减少缺氧诱导的培养心肌细胞和H9C2心肌母细胞中线粒体ROS的产生。另外，维生素E TPGS / Apelin赋予细胞对缺氧应激的凋亡反应。在异丙肾上腺素引起的心脏损伤的小鼠模型中，TPGS不能影响心脏重塑，但是维生素E TPGS和Apelin的组合可抵消心肌细胞凋亡，氧化应激，肥大和纤维化。此外，联合治疗可减轻肥胖引起的小鼠心脏代谢和纤维化重塑。结论综上所述，我们的数据证明了维生素E TPGS / Apelin复合物可对抗心血管疾病和代谢疾病。维生素E TPGS / Apelin赋予细胞对缺氧应激的凋亡反应。在异丙肾上腺素引起的心脏损伤的小鼠模型中，TPGS不能影响心脏重塑，但是维生素E TPGS和Apelin的组合可抵消心肌细胞凋亡，氧化应激，肥大和纤维化。此外，联合治疗可减轻肥胖引起的小鼠心脏代谢和纤维化重塑。结论综上所述，我们的数据证明了维生素E TPGS / Apelin复合物可对抗心血管疾病和代谢疾病。维生素E TPGS / Apelin赋予细胞对缺氧应激的凋亡反应。在异丙肾上腺素引起的心脏损伤的小鼠模型中，TPGS不能影响心脏重塑，但是维生素E TPGS和Apelin的组合可抵消心肌细胞凋亡，氧化应激，肥大和纤维化。此外，联合治疗可减轻肥胖引起的小鼠心脏代谢和纤维化重塑。结论综上所述，我们的数据证明了维生素E TPGS / Apelin复合物可对抗心血管疾病和代谢疾病。肥大和纤维化。此外，联合治疗可减轻肥胖引起的小鼠心脏代谢和纤维化重塑。结论综上所述，我们的数据证明了维生素E TPGS / Apelin复合物具有抗心血管和代谢疾病的治疗作用。肥大和纤维化。此外，联合治疗可减轻肥胖引起的小鼠心脏代谢和纤维化重塑。结论综上所述，我们的数据证明了维生素E TPGS / Apelin复合物可对抗心血管疾病和代谢疾病。