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J Mol Cell Cardiol. 2019 Dec 10;138:165-174. doi: 10.1016/j.yjmcc.2019.12.001. [Epub ahead of print]

In vitro and in vivo cardioprotective and metabolic efficacy of vitamin E TPGS/Apelin.

Author information

1
Laboratoire des IMRCP, Université de Toulouse, CNRS UMR 5623, Université Toulouse III - Paul Sabatier, France.
2
INSERM U1048 I2MC, Toulouse, France; Université Paul Sabatier, Toulouse, France.
3
INSERM U1048 I2MC, Toulouse, France; Université Paul Sabatier, Toulouse, France. Electronic address: frederic.boal@inserm.fr.

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.

KEYWORDS:

Cardiac hypertrophy; Obesity; Oxidative stress; Surfactant

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