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Article

Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II

1
Department of Pharmacology, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
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Department of Pathology, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
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Department of Molecular Biology, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
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Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y de la Nutrición “Salvador Zubirán”, Vasco de Quiroga 15, Sección XVI, Tlalpan, México City 14000, Mexico
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Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, México City 04510, Mexico
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Department of Physiology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
*
Author to whom correspondence should be addressed.
L.I.-L. and M.S.-A. share the first authorship of this paper.
Academic Editors: Luciano Saso, László Dux, Grzegorz Wegrzyn and Tamás Csont
Molecules 2017, 22(1), 31; https://doi.org/10.3390/molecules22010031
Received: 24 October 2016 / Revised: 4 December 2016 / Accepted: 20 December 2016 / Published: 28 December 2016
(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)
Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II)/Angiotensin II type 1 receptor (AT1) and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia. Control and MetS rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); and (c) fenofibrate-treated myocardial infarction (MI-F). Treatment with fenofibrate significantly reduced triglycerides, non-high density lipoprotein cholesterol (non-HDL-C), insulin levels and insulin resistance index (HOMA-IR) in MetS animals. MetS and MI increased Ang II concentration and AT1 expression, favored myocardial oxidative stress (high levels of malondialdehyde, overexpression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), decreased total antioxidant capacity and diminished expression of superoxide dismutase (SOD)1, SOD2 and catalase) and inhibited expression of the insulin signaling cascade: phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PkB, also known as Akt)/Glut-4/endothelial nitric oxide synthase (eNOS). In conclusion, fenofibrate treatment favors an antioxidant environment as a consequence of a reduction of the Ang II/AT1/NOX4 signaling pathway, reestablishing the cardiac insulin signaling pathway. This might optimize cardiac metabolism and improve the vasodilator function during myocardial ischemia. View Full-Text
Keywords: metabolic syndrome; insulin resistance; myocardial ischemia; fenofibrate; oxidative stress; angiotensin II metabolic syndrome; insulin resistance; myocardial ischemia; fenofibrate; oxidative stress; angiotensin II
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MDPI and ACS Style

Ibarra-Lara, L.; Sánchez-Aguilar, M.; Sánchez-Mendoza, A.; Del Valle-Mondragón, L.; Soria-Castro, E.; Carreón-Torres, E.; Díaz-Díaz, E.; Vázquez-Meza, H.; Guarner-Lans, V.; Rubio-Ruiz, M.E. Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II. Molecules 2017, 22, 31. https://doi.org/10.3390/molecules22010031

AMA Style

Ibarra-Lara L, Sánchez-Aguilar M, Sánchez-Mendoza A, Del Valle-Mondragón L, Soria-Castro E, Carreón-Torres E, Díaz-Díaz E, Vázquez-Meza H, Guarner-Lans V, Rubio-Ruiz ME. Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II. Molecules. 2017; 22(1):31. https://doi.org/10.3390/molecules22010031

Chicago/Turabian Style

Ibarra-Lara, Luz, María Sánchez-Aguilar, Alicia Sánchez-Mendoza, Leonardo Del Valle-Mondragón, Elizabeth Soria-Castro, Elizabeth Carreón-Torres, Eulises Díaz-Díaz, Héctor Vázquez-Meza, Verónica Guarner-Lans, and María E. Rubio-Ruiz 2017. "Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II" Molecules 22, no. 1: 31. https://doi.org/10.3390/molecules22010031

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