View source for De la Rosa Vargas 2019 Arch Cardiovasc Dis

{{Abstract
|title=De la Rosa Vargas LE, Dale Abel E, Langer T, Wai T (2019) Metabolic regulation of heart failure caused by imbalanced mitochondrial dynamics. Arch Cardiovasc Dis.
|info=[https://www.sciencedirect.com/science/article/pii/S1878648019301855 Open Access]
|authors=De la Rosa Vargas LE, Dale Abel E, Langer T, Wai T
|year=2019
|event=Arch Cardiovasc Dis
|abstract=Dilated Cardiomyopathy (DCM) is characterized by an expansion of the left ventricle having as a consequence inefficient oxygenated blood pumping to the body. DCM can result in heart failure and is the most common cause of heart transplantation. The healthy adult heart relies mainly on free fatty acids as its main fuel source and rather than glucose but in the failing heart, a metabolic switch away from fatty acid oxidation and towards glucose uptake has been observed and has been proposed to represent an adaptive bioenergetic mechanism. We developed a mouse model of DCM caused by mitochondrial fragmentation in cardiomyocytes due to the deletion of the mitochondrial protease YME1L. This mouse model recapitulates all the clinical features of DCM as well as the metabolic features, such as cardiac glucose overload, progressing into chronic heart failure and middle-aged death.

Using our DCM mouse model, we will test whether reducing cardiac glucose overload to the heart diminishes or exacerbates cardiac and metabolic dysfunction. To his end, we will ablate the primary glucose transporter GLUT 4 either partially or completely in DCM mice to diminish glucose uptake to the heart.

We generated cardiac specific deletions of YME1L and GLUT4 by crossing the cardiomyocyte specific Cre-recombinase drive Myh6-Cre to conditional YME1LLoxp/LoxP and SLC2A4Loxp/LoxP mice. Cardiac function will be assessed using echocardiography and mitochondrial activity using high resolution oxygraphy (Oroboros) in isolated cardiac mitochondria.

Our studies will allow us to determine the importance of glucose uptake and usage in the failing adult heart.
|editor=[[Plangger M]],
}}
{{Labeling
|area=Respiration
|diseases=Cardiovascular
|organism=Mouse
|tissues=Heart
|preparations=Isolated mitochondria
|instruments=Oxygraph-2k
}}
== Affiliations ==
De la Rosa Vargas LE(1), Dale Abel E(2), Langer T(3,4), Wai T(1)
::::#Univ Paris Descartes-Sorbonne
::::#Inst Pasteur; Paris, France
::::#Carver College Medicine, IA, US
::::#Max Planck Inst Biology Ageing, Cologne, Germany