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...
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10459 |
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| author | Ana-Maria Gan Zuzanna Tracz-Gaszewska Aleksandra Ellert-Miklaszewska Viktor O. Navrulin James M. Ntambi Pawel Dobrzyn |
| author_facet | Ana-Maria Gan Zuzanna Tracz-Gaszewska Aleksandra Ellert-Miklaszewska Viktor O. Navrulin James M. Ntambi Pawel Dobrzyn |
| author_sort | Ana-Maria Gan |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T23:46:23Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:46:23Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0f9c5f46fc1242d2997ab8b5465f839c2023-11-23T16:42:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181045910.3390/ijms231810459Stearoyl-CoA Desaturase Regulates Angiogenesis and Energy Metabolism in Ischemic CardiomyocytesAna-Maria Gan0Zuzanna Tracz-Gaszewska1Aleksandra Ellert-Miklaszewska2Viktor O. Navrulin3James M. Ntambi4Pawel Dobrzyn5Laboratory of Molecular Medical Biochemistry, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandLaboratory of Molecular Medical Biochemistry, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandLaboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandLaboratory of Molecular Medical Biochemistry, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandDepartments of Biochemistry and Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USALaboratory of Molecular Medical Biochemistry, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandNew 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.https://www.mdpi.com/1422-0067/23/18/10459heartcytokineshypoxiafatty acidssubstrate utilization |
| spellingShingle | Ana-Maria Gan Zuzanna Tracz-Gaszewska Aleksandra Ellert-Miklaszewska Viktor O. Navrulin James M. Ntambi Pawel Dobrzyn Stearoyl-CoA Desaturase Regulates Angiogenesis and Energy Metabolism in Ischemic Cardiomyocytes International Journal of Molecular Sciences heart cytokines hypoxia fatty acids substrate utilization |
| 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 | heart cytokines hypoxia fatty acids substrate utilization |
| url | https://www.mdpi.com/1422-0067/23/18/10459 |
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