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Stearoyl-CoA Desaturase Regulates Angiogenesis and Energy Metabolism in Ischemic Cardiomyocytes
New blood vessel formation is a key component of the cardiac repair process after myocardial infarction (MI). Hypoxia following MI is a major driver of angiogenesis in the myocardium. Hypoxia-inducible factor 1α (HIF1α) is the key regulator of proangiogenic signaling. The present study found that st...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499489/ https://www.ncbi.nlm.nih.gov/pubmed/36142371 http://dx.doi.org/10.3390/ijms231810459 |
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author | Gan, Ana-Maria Tracz-Gaszewska, Zuzanna Ellert-Miklaszewska, Aleksandra Navrulin, Viktor O. Ntambi, James M. Dobrzyn, Pawel |
author_facet | Gan, Ana-Maria Tracz-Gaszewska, Zuzanna Ellert-Miklaszewska, Aleksandra Navrulin, Viktor O. Ntambi, James M. Dobrzyn, Pawel |
author_sort | Gan, Ana-Maria |
collection | PubMed |
description | New blood vessel formation is a key component of the cardiac repair process after myocardial infarction (MI). Hypoxia following MI is a major driver of angiogenesis in the myocardium. Hypoxia-inducible factor 1α (HIF1α) is the key regulator of proangiogenic signaling. The present study found that stearoyl-CoA desaturase (SCD) significantly contributed to the induction of angiogenesis in the hypoxic myocardium independently of HIF1α expression. The pharmacological inhibition of SCD activity in HL-1 cardiomyocytes and SCD knockout in an animal model disturbed the expression and secretion of proangiogenic factors including vascular endothelial growth factor-A, proinflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor α, monocyte chemoattractant protein-1, and Rantes), metalloproteinase-9, and platelet-derived growth factor in ischemic cardiomyocytes. These disturbances affected the proangiogenic potential of ischemic cardiomyocytes after SCD depletion. Together with the most abundant SCD1 isoform, the heart-specific SCD4 isoform emerged as an important regulator of new blood vessel formation in the murine post-MI myocardium. We also provide evidence that SCD shapes energy metabolism of the ischemic heart by maintaining the shift from fatty acids to glucose as the substrate that is used for adenosine triphosphate production. Furthermore, we propose that the regulation of the proangiogenic properties of hypoxic cardiomyocytes by key modulators of metabolic signaling such as adenosine monophosphate kinase, protein kinase B (AKT), and peroxisome-proliferator-activated receptor-γ coactivator 1α/peroxisome proliferator-activated receptor α depends on SCD to some extent. Thus, our results reveal a novel mechanism that links SCD to cardiac repair processes after MI. |
format | Online Article Text |
id | pubmed-9499489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94994892022-09-23 Stearoyl-CoA Desaturase Regulates Angiogenesis and Energy Metabolism in Ischemic Cardiomyocytes Gan, Ana-Maria Tracz-Gaszewska, Zuzanna Ellert-Miklaszewska, Aleksandra Navrulin, Viktor O. Ntambi, James M. Dobrzyn, Pawel Int J Mol Sci Article New blood vessel formation is a key component of the cardiac repair process after myocardial infarction (MI). Hypoxia following MI is a major driver of angiogenesis in the myocardium. Hypoxia-inducible factor 1α (HIF1α) is the key regulator of proangiogenic signaling. The present study found that stearoyl-CoA desaturase (SCD) significantly contributed to the induction of angiogenesis in the hypoxic myocardium independently of HIF1α expression. The pharmacological inhibition of SCD activity in HL-1 cardiomyocytes and SCD knockout in an animal model disturbed the expression and secretion of proangiogenic factors including vascular endothelial growth factor-A, proinflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor α, monocyte chemoattractant protein-1, and Rantes), metalloproteinase-9, and platelet-derived growth factor in ischemic cardiomyocytes. These disturbances affected the proangiogenic potential of ischemic cardiomyocytes after SCD depletion. Together with the most abundant SCD1 isoform, the heart-specific SCD4 isoform emerged as an important regulator of new blood vessel formation in the murine post-MI myocardium. We also provide evidence that SCD shapes energy metabolism of the ischemic heart by maintaining the shift from fatty acids to glucose as the substrate that is used for adenosine triphosphate production. Furthermore, we propose that the regulation of the proangiogenic properties of hypoxic cardiomyocytes by key modulators of metabolic signaling such as adenosine monophosphate kinase, protein kinase B (AKT), and peroxisome-proliferator-activated receptor-γ coactivator 1α/peroxisome proliferator-activated receptor α depends on SCD to some extent. Thus, our results reveal a novel mechanism that links SCD to cardiac repair processes after MI. MDPI 2022-09-09 /pmc/articles/PMC9499489/ /pubmed/36142371 http://dx.doi.org/10.3390/ijms231810459 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gan, Ana-Maria Tracz-Gaszewska, Zuzanna Ellert-Miklaszewska, Aleksandra Navrulin, Viktor O. Ntambi, James M. Dobrzyn, Pawel Stearoyl-CoA Desaturase Regulates Angiogenesis and Energy Metabolism in Ischemic Cardiomyocytes |
title | Stearoyl-CoA Desaturase Regulates Angiogenesis and Energy Metabolism in Ischemic Cardiomyocytes |
title_full | Stearoyl-CoA Desaturase Regulates Angiogenesis and Energy Metabolism in Ischemic Cardiomyocytes |
title_fullStr | Stearoyl-CoA Desaturase Regulates Angiogenesis and Energy Metabolism in Ischemic Cardiomyocytes |
title_full_unstemmed | Stearoyl-CoA Desaturase Regulates Angiogenesis and Energy Metabolism in Ischemic Cardiomyocytes |
title_short | Stearoyl-CoA Desaturase Regulates Angiogenesis and Energy Metabolism in Ischemic Cardiomyocytes |
title_sort | stearoyl-coa desaturase regulates angiogenesis and energy metabolism in ischemic cardiomyocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499489/ https://www.ncbi.nlm.nih.gov/pubmed/36142371 http://dx.doi.org/10.3390/ijms231810459 |
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