Altered Left Ventricular Rat Gene Expression Induced by the Myosin Activator Omecamtiv Mecarbil
To explore the impact of omecamtiv mecarbil (OM) on the gene expression profile in adult male rats. Fourteen male Wistar rats were randomly assigned to a single OM (1.2 mg/kg/h; n = 6) or placebo (n = 8) 30-min infusion. Echocardiography was performed before and after OM infusion. Seven days after i...
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MDPI AG
2023-01-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/1/122 |
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| author | Bachar El Oumeiri Laurence Dewachter Philippe Van de Borne Géraldine Hubesch Christian Melot Pascale Jespers Constantin Stefanidis Kathleen Mc Entee Frédéric Vanden Eynden |
| author_facet | Bachar El Oumeiri Laurence Dewachter Philippe Van de Borne Géraldine Hubesch Christian Melot Pascale Jespers Constantin Stefanidis Kathleen Mc Entee Frédéric Vanden Eynden |
| author_sort | Bachar El Oumeiri |
| collection | DOAJ |
| description | To explore the impact of omecamtiv mecarbil (OM) on the gene expression profile in adult male rats. Fourteen male Wistar rats were randomly assigned to a single OM (1.2 mg/kg/h; n = 6) or placebo (n = 8) 30-min infusion. Echocardiography was performed before and after OM infusion. Seven days after infusion, rats were euthanized, and left ventricular (LV) tissues were removed for <i>real-time</i> quantitative polymerase chain reaction (RTq-PCR) experiments. After OM infusion, pro-apoptotic <i>Bax</i>-to-<i>Bcl2</i> ratio was decreased, with increased <i>Bcl2</i> and similar <i>Bax</i> gene expression. The gene expression of molecules regulating oxidative stress, including glutathione disulfide reductase (<i>Gsr</i>) and superoxide dismutases (<i>Sod1</i>/<i>Sod2</i>), remained unchanged, whereas the expression of antioxidant glutathione peroxidase (<i>Gpx</i>) increased. While LV gene expression of key energy sensors, peroxisome proliferator activator (<i>Ppar</i>) α and γ, AMP-activated protein kinase (<i>Ampk</i>), and carnitine palmitoyltransferase 1 (<i>Cpt1</i>) remained unchanged after OM infusion, and the expression of pyruvate dehydrogenase kinase 4 (<i>Pdk4</i>) increased. The LV expression of the major myocardial glucose transporter <i>Glut1</i> decreased, with no changes in <i>Glut4</i> expression, whereas the LV expression of oxidized low-density lipoprotein receptor 1 (<i>Olr1</i>) and arachidonate 15-lipoxygenase (<i>Alox15</i>) increased, with no changes in fatty acid transporter <i>Cd36</i>. An increased LV expression of angiotensin II receptors <i>AT1</i> and <i>AT2</i> was observed, with no changes in angiotensin I-converting enzyme expression. The Kalikrein-bradykinin system was upregulated with increased LV expression of kallikrein-related peptidases <i>Klk8</i>, <i>Klk1c2</i>, and <i>Klk1c12</i> and bradykinin receptors B1 and B2 (<i>Bdkrb1</i> and <i>Bdkrb2</i>), whereas the LV expression of inducible nitric oxide synthase 2 (<i>Nos2</i>) increased. LV expression in major molecular determinants involved in calcium-dependent myocardial contraction remained unchanged, except for an increased LV expression of calcium/calmodulin-dependent protein kinase II delta (<i>Cacna1c</i>) in response to OM. A single intravenous infusion of OM, in adult healthy rats, resulted in significant changes in the LV expression of genes regulating apoptosis, oxidative stress, metabolism, and cardiac contractility. |
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| institution | Directory Open Access Journal |
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| last_indexed | 2024-03-09T12:36:24Z |
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| series | Genes |
| spelling | doaj.art-e444de2f82fd49dca2adf0717f506cd32023-11-30T22:23:52ZengMDPI AGGenes2073-44252023-01-0114112210.3390/genes14010122Altered Left Ventricular Rat Gene Expression Induced by the Myosin Activator Omecamtiv MecarbilBachar El Oumeiri0Laurence Dewachter1Philippe Van de Borne2Géraldine Hubesch3Christian Melot4Pascale Jespers5Constantin Stefanidis6Kathleen Mc Entee7Frédéric Vanden Eynden8Department of Cardiac Surgery, Université Libre de Bruxelles (ULB) Erasme University Hospital, 1070 Brussels, BelgiumLaboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles (ULB), 1070 Brussels, BelgiumDepartment of Cardiology, Université Libre de Bruxelles (ULB) Erasme University Hospital, 1070 Brussels, BelgiumLaboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles (ULB), 1070 Brussels, BelgiumLaboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles (ULB), 1070 Brussels, BelgiumLaboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles (ULB), 1070 Brussels, BelgiumDepartment of Cardiac Surgery, Université Libre de Bruxelles (ULB) Erasme University Hospital, 1070 Brussels, BelgiumLaboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles (ULB), 1070 Brussels, BelgiumDepartment of Cardiac Surgery, Université Libre de Bruxelles (ULB) Erasme University Hospital, 1070 Brussels, BelgiumTo explore the impact of omecamtiv mecarbil (OM) on the gene expression profile in adult male rats. Fourteen male Wistar rats were randomly assigned to a single OM (1.2 mg/kg/h; n = 6) or placebo (n = 8) 30-min infusion. Echocardiography was performed before and after OM infusion. Seven days after infusion, rats were euthanized, and left ventricular (LV) tissues were removed for <i>real-time</i> quantitative polymerase chain reaction (RTq-PCR) experiments. After OM infusion, pro-apoptotic <i>Bax</i>-to-<i>Bcl2</i> ratio was decreased, with increased <i>Bcl2</i> and similar <i>Bax</i> gene expression. The gene expression of molecules regulating oxidative stress, including glutathione disulfide reductase (<i>Gsr</i>) and superoxide dismutases (<i>Sod1</i>/<i>Sod2</i>), remained unchanged, whereas the expression of antioxidant glutathione peroxidase (<i>Gpx</i>) increased. While LV gene expression of key energy sensors, peroxisome proliferator activator (<i>Ppar</i>) α and γ, AMP-activated protein kinase (<i>Ampk</i>), and carnitine palmitoyltransferase 1 (<i>Cpt1</i>) remained unchanged after OM infusion, and the expression of pyruvate dehydrogenase kinase 4 (<i>Pdk4</i>) increased. The LV expression of the major myocardial glucose transporter <i>Glut1</i> decreased, with no changes in <i>Glut4</i> expression, whereas the LV expression of oxidized low-density lipoprotein receptor 1 (<i>Olr1</i>) and arachidonate 15-lipoxygenase (<i>Alox15</i>) increased, with no changes in fatty acid transporter <i>Cd36</i>. An increased LV expression of angiotensin II receptors <i>AT1</i> and <i>AT2</i> was observed, with no changes in angiotensin I-converting enzyme expression. The Kalikrein-bradykinin system was upregulated with increased LV expression of kallikrein-related peptidases <i>Klk8</i>, <i>Klk1c2</i>, and <i>Klk1c12</i> and bradykinin receptors B1 and B2 (<i>Bdkrb1</i> and <i>Bdkrb2</i>), whereas the LV expression of inducible nitric oxide synthase 2 (<i>Nos2</i>) increased. LV expression in major molecular determinants involved in calcium-dependent myocardial contraction remained unchanged, except for an increased LV expression of calcium/calmodulin-dependent protein kinase II delta (<i>Cacna1c</i>) in response to OM. A single intravenous infusion of OM, in adult healthy rats, resulted in significant changes in the LV expression of genes regulating apoptosis, oxidative stress, metabolism, and cardiac contractility.https://www.mdpi.com/2073-4425/14/1/122left ventricleomecamtiv mecarbilgene expressionapoptosismetabolismoxidative stress |
| spellingShingle | Bachar El Oumeiri Laurence Dewachter Philippe Van de Borne Géraldine Hubesch Christian Melot Pascale Jespers Constantin Stefanidis Kathleen Mc Entee Frédéric Vanden Eynden Altered Left Ventricular Rat Gene Expression Induced by the Myosin Activator Omecamtiv Mecarbil Genes left ventricle omecamtiv mecarbil gene expression apoptosis metabolism oxidative stress |
| title | Altered Left Ventricular Rat Gene Expression Induced by the Myosin Activator Omecamtiv Mecarbil |
| title_full | Altered Left Ventricular Rat Gene Expression Induced by the Myosin Activator Omecamtiv Mecarbil |
| title_fullStr | Altered Left Ventricular Rat Gene Expression Induced by the Myosin Activator Omecamtiv Mecarbil |
| title_full_unstemmed | Altered Left Ventricular Rat Gene Expression Induced by the Myosin Activator Omecamtiv Mecarbil |
| title_short | Altered Left Ventricular Rat Gene Expression Induced by the Myosin Activator Omecamtiv Mecarbil |
| title_sort | altered left ventricular rat gene expression induced by the myosin activator omecamtiv mecarbil |
| topic | left ventricle omecamtiv mecarbil gene expression apoptosis metabolism oxidative stress |
| url | https://www.mdpi.com/2073-4425/14/1/122 |
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