1. In vitro and in vivo cardioprotective and metabolic efficacy of vitamin E TPGS/Apelin.
- Author
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Leme Goto P, Cinato M, Merachli F, Vons B, Jimenez T, Marsal D, Todua N, Loi H, Santin Y, Cassel S, Blanzat M, Tronchere H, Dejugnat C, Kunduzova O, and Boal F
- Subjects
- Animals, Apoptosis drug effects, Cardiomegaly complications, Cardiomegaly pathology, Cell Hypoxia drug effects, Cell Line, Diabetic Cardiomyopathies complications, Diabetic Cardiomyopathies pathology, Diet, High-Fat, Fibrosis, Isoproterenol, Mice, Inbred C57BL, Mitochondria drug effects, Mitochondria metabolism, Myocytes, Cardiac drug effects, Myocytes, Cardiac metabolism, Oxidative Stress drug effects, Rats, Reactive Oxygen Species metabolism, Vascular Remodeling drug effects, Apelin pharmacology, Cardiotonic Agents pharmacology, Vitamin E pharmacology
- Abstract
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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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