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Article

Hypoxia-Inducible Factor 1-Alpha and Glucose Metabolism during Cardiac Remodeling Progression from Hypertrophy to Heart Failure

by
Paula Grippa Sant’Ana
1,
Loreta Casquel de Tomasi
1,
Gilson Masahiro Murata
2,
Danielle Fernandes Vileigas
1,†,
Gustavo Augusto Ferreira Mota
1,
Sérgio Luiz Borges de Souza
1,
Vitor Loureiro Silva
1,
Livia Paschoalino de Campos
3,
Katashi Okoshi
1,
Carlos Roberto Padovani
3 and
Antonio Carlos Cicogna
1,*
1
Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), Botucatu 18618-687, Brazil
2
Laboratory of Medical Investigation (LIM-29), Division of Nephrology, University of São Paulo Medical School, São Paulo 01246-903, Brazil
3
Department of Biostatistics, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-689, Brazil
*
Author to whom correspondence should be addressed.
†
Current address: Department of Biochemistry, Institute of Chemistry, University of São Paulo (USP), São Paulo 05508-000, Brazil.
Int. J. Mol. Sci. 2023, 24(7), 6201; https://doi.org/10.3390/ijms24076201
Submission received: 1 February 2023 / Revised: 7 March 2023 / Accepted: 8 March 2023 / Published: 25 March 2023
(This article belongs to the Special Issue Cardiovascular Disease and Myocardial Metabolism)
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Abstract

In pathological cardiac hypertrophy, the heart is more dependent on glucose than fatty acids. This shift in energy metabolism occurs due to several factors, including the oxygen deficit, which activates hypoxia-inducible factor-1α (HIF-1α), a critical molecule related to glucose metabolism. However, there are gaps regarding the behavior of key proteins in the glycolytic pathway and HIF-1α during the transition from hypertrophy to heart failure (HF). This study assesses the hypothesis that there is an early change and enhancement of HIF-1α and the glycolytic pathway, as well as an association between them during cardiac remodeling. Sham and aortic stenosis Wistar rats were analyzed at 2, 6, and 18 weeks and in HF (n = 10–18). Cardiac structure and function were investigated by echocardiogram. Myocardial glycolysis, the aerobic and anaerobic pathways and glycogen were analyzed by enzymatic assay, Western blot, and enzyme-linked immunosorbent assay (ELISA). The following were observed: increased left ventricular hypertrophy; early diastolic function change and severe systolic and diastolic dysfunction in HF; increased HIF-1α in the 2nd week and in HF; precocious alteration and intensification of glycolysis with a shift to anaerobic metabolism from the 6th week onwards; association between HIF-1α, glycolysis, and the anaerobic pathway. Our hypothesis was confirmed as there was an early change and intensification in glucose metabolism, alteration in HIF-1α, and an association between data during the progression from hypertrophy to heart failure.
Keywords: aortic stenosis; cardiac remodeling; HIF-1α; glucose metabolism; rats aortic stenosis; cardiac remodeling; HIF-1α; glucose metabolism; rats

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MDPI and ACS Style

Sant’Ana, P.G.; Tomasi, L.C.d.; Murata, G.M.; Vileigas, D.F.; Mota, G.A.F.; Souza, S.L.B.d.; Silva, V.L.; Campos, L.P.d.; Okoshi, K.; Padovani, C.R.; et al. Hypoxia-Inducible Factor 1-Alpha and Glucose Metabolism during Cardiac Remodeling Progression from Hypertrophy to Heart Failure. Int. J. Mol. Sci. 2023, 24, 6201. https://doi.org/10.3390/ijms24076201

AMA Style

Sant’Ana PG, Tomasi LCd, Murata GM, Vileigas DF, Mota GAF, Souza SLBd, Silva VL, Campos LPd, Okoshi K, Padovani CR, et al. Hypoxia-Inducible Factor 1-Alpha and Glucose Metabolism during Cardiac Remodeling Progression from Hypertrophy to Heart Failure. International Journal of Molecular Sciences. 2023; 24(7):6201. https://doi.org/10.3390/ijms24076201

Chicago/Turabian Style

Sant’Ana, Paula Grippa, Loreta Casquel de Tomasi, Gilson Masahiro Murata, Danielle Fernandes Vileigas, Gustavo Augusto Ferreira Mota, Sérgio Luiz Borges de Souza, Vitor Loureiro Silva, Livia Paschoalino de Campos, Katashi Okoshi, Carlos Roberto Padovani, and et al. 2023. "Hypoxia-Inducible Factor 1-Alpha and Glucose Metabolism during Cardiac Remodeling Progression from Hypertrophy to Heart Failure" International Journal of Molecular Sciences 24, no. 7: 6201. https://doi.org/10.3390/ijms24076201

APA Style

Sant’Ana, P. G., Tomasi, L. C. d., Murata, G. M., Vileigas, D. F., Mota, G. A. F., Souza, S. L. B. d., Silva, V. L., Campos, L. P. d., Okoshi, K., Padovani, C. R., & Cicogna, A. C. (2023). Hypoxia-Inducible Factor 1-Alpha and Glucose Metabolism during Cardiac Remodeling Progression from Hypertrophy to Heart Failure. International Journal of Molecular Sciences, 24(7), 6201. https://doi.org/10.3390/ijms24076201

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