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Article

Proteomics of Mouse Heart Ventricles Reveals Mitochondria and Metabolism as Major Targets of a Post-Infarction Short-Acting GLP1Ra-Therapy

1
Cedars-Sinai Medical Center, Smidt Heart Institute, Beverly Hills, CA 90048, USA
2
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, 0310 Oslo, Norway
3
KG Jebsen Centre for B-Cell Malignancies, Institute for Clinical Medicine, University of Oslo, 0318 Oslo, Norway
4
Institute of Analytical Chemistry of the Czech Academy of Sciences, 60200 Brno, Czech Republic
*
Authors to whom correspondence should be addressed.
Academic Editors: Maria Gonzalez Barderas and Fernando de la Cuesta
Int. J. Mol. Sci. 2021, 22(16), 8711; https://doi.org/10.3390/ijms22168711
Received: 16 June 2021 / Revised: 11 July 2021 / Accepted: 16 July 2021 / Published: 13 August 2021
(This article belongs to the Special Issue Molecular Mechanisms and Pathophysiology of Cardiovascular Disease)
Cardiovascular disease is the main cause of death worldwide, making it crucial to search for new therapies to mitigate major adverse cardiac events (MACEs) after a cardiac ischemic episode. Drugs in the class of the glucagon-like peptide-1 receptor agonists (GLP1Ra) have demonstrated benefits for heart function and reduced the incidence of MACE in patients with diabetes. Previously, we demonstrated that a short-acting GLP1Ra known as DMB (2-quinoxalinamine, 6,7-dichloro-N-[1,1-dimethylethyl]-3-[methylsulfonyl]-,6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline or compound 2, Sigma) also mitigates adverse postinfarction left ventricular remodeling and cardiac dysfunction in lean mice through activation of parkin-mediated mitophagy following infarction. Here, we combined proteomics with in silico analysis to characterize the range of effects of DMB in vivo throughout the course of early postinfarction remodeling. We demonstrate that the mitochondrion is a key target of DMB and mitochondrial respiration, oxidative phosphorylation and metabolic processes such as glycolysis and fatty acid beta-oxidation are the main biological processes being regulated by this compound in the heart. Moreover, the overexpression of proteins with hub properties identified by protein–protein interaction networks, such as Atp2a2, may also be important to the mechanism of action of DMB. Data are available via ProteomeXchange with identifier PXD027867. View Full-Text
Keywords: proteomics; glucagon-like peptide-1 receptor agonists; DMB; early cardiac remodeling; mitochondrion; cellular respiration; metabolism proteomics; glucagon-like peptide-1 receptor agonists; DMB; early cardiac remodeling; mitochondrion; cellular respiration; metabolism
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MDPI and ACS Style

de Freitas Germano, J.; Sharma, A.; Stastna, M.; Huang, C.; Aniag, M.; Aceves, A.; Van Eyk, J.E.; Mentzer, R.M., Jr.; Piplani, H.; Andres, A.M.; Gottlieb, R.A. Proteomics of Mouse Heart Ventricles Reveals Mitochondria and Metabolism as Major Targets of a Post-Infarction Short-Acting GLP1Ra-Therapy. Int. J. Mol. Sci. 2021, 22, 8711. https://doi.org/10.3390/ijms22168711

AMA Style

de Freitas Germano J, Sharma A, Stastna M, Huang C, Aniag M, Aceves A, Van Eyk JE, Mentzer RM Jr., Piplani H, Andres AM, Gottlieb RA. Proteomics of Mouse Heart Ventricles Reveals Mitochondria and Metabolism as Major Targets of a Post-Infarction Short-Acting GLP1Ra-Therapy. International Journal of Molecular Sciences. 2021; 22(16):8711. https://doi.org/10.3390/ijms22168711

Chicago/Turabian Style

de Freitas Germano, Juliana, Ankush Sharma, Miroslava Stastna, Chengqun Huang, Marianne Aniag, Angie Aceves, Jennifer E. Van Eyk, Robert M. Mentzer Jr., Honit Piplani, Allen M. Andres, and Roberta A. Gottlieb. 2021. "Proteomics of Mouse Heart Ventricles Reveals Mitochondria and Metabolism as Major Targets of a Post-Infarction Short-Acting GLP1Ra-Therapy" International Journal of Molecular Sciences 22, no. 16: 8711. https://doi.org/10.3390/ijms22168711

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