Activation of a GPCR, ORL1 Receptor: A Novel Therapy to Prevent Heart Failure Progression
The number of ischemic heart failure (HF) patients is growing dramatically worldwide. However, there are at present no preventive treatments for HF. Our previous study showed that Gata4 overexpression improved cardiac function after myocardial infarction in rat hearts. We also found that Gata4 overe...
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2024-11-01
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| author | Saliha S. Pathan Aarthi Pugazenthi Beverly R. E. A. Dixon Theodore G. Wensel Todd K. Rosengart Megumi Mathison |
| author_facet | Saliha S. Pathan Aarthi Pugazenthi Beverly R. E. A. Dixon Theodore G. Wensel Todd K. Rosengart Megumi Mathison |
| author_sort | Saliha S. Pathan |
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| description | The number of ischemic heart failure (HF) patients is growing dramatically worldwide. However, there are at present no preventive treatments for HF. Our previous study showed that Gata4 overexpression improved cardiac function after myocardial infarction in rat hearts. We also found that Gata4 overexpression significantly increased the expression of a Pnoc gene, an endogenous ligand for the cell membrane receptor ORL1. We hypothesized that the activation of the ORL1 receptor would suppress HF in a rat ischemic heart model. Adult Sprague Dawley rats (8 weeks old, six males and six females) underwent left anterior descending coronary artery ligation. Three weeks later, normal saline or MCOPPB (ORL1 activator, 2.5 mg/kg/day) intraperitoneal injection was started, and continued 5 days a week for 3 months. Echocardiography was performed six times: pre-operative, 3 days after coronary artery ligation, pre-MCOPPB or saline injection, and 1, 2, and 3 months after saline or MCOPPB injection started. Animals were euthanized after 3 months’ follow-up and the hearts were harvested for histological analysis. The ORL1 activator, MCOPPB, significantly improved cardiac function after myocardial infarction in rats (ejection fraction, MCOPPB vs. saline at euthanasia, 67 ± 3% vs. 43 ± 2%, <i>p</i> < 0.001). MCOPPB also decreased fibrosis and induced angiogenesis. Thus, the ORL1 activator, MCOPPB, may be a novel treatment for preventing HF progression. |
| format | Article |
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| institution | OA Journals |
| issn | 2308-3425 |
| language | English |
| publishDate | 2024-11-01 |
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| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj-art-be5a8326140a4065aaf1f0c4db5dff102025-08-20T01:54:07ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252024-11-01111135510.3390/jcdd11110355Activation of a GPCR, ORL1 Receptor: A Novel Therapy to Prevent Heart Failure ProgressionSaliha S. Pathan0Aarthi Pugazenthi1Beverly R. E. A. Dixon2Theodore G. Wensel3Todd K. Rosengart4Megumi Mathison5Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USAMichael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USAMichael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USADepartment of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USAMichael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USAMichael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USAThe number of ischemic heart failure (HF) patients is growing dramatically worldwide. However, there are at present no preventive treatments for HF. Our previous study showed that Gata4 overexpression improved cardiac function after myocardial infarction in rat hearts. We also found that Gata4 overexpression significantly increased the expression of a Pnoc gene, an endogenous ligand for the cell membrane receptor ORL1. We hypothesized that the activation of the ORL1 receptor would suppress HF in a rat ischemic heart model. Adult Sprague Dawley rats (8 weeks old, six males and six females) underwent left anterior descending coronary artery ligation. Three weeks later, normal saline or MCOPPB (ORL1 activator, 2.5 mg/kg/day) intraperitoneal injection was started, and continued 5 days a week for 3 months. Echocardiography was performed six times: pre-operative, 3 days after coronary artery ligation, pre-MCOPPB or saline injection, and 1, 2, and 3 months after saline or MCOPPB injection started. Animals were euthanized after 3 months’ follow-up and the hearts were harvested for histological analysis. The ORL1 activator, MCOPPB, significantly improved cardiac function after myocardial infarction in rats (ejection fraction, MCOPPB vs. saline at euthanasia, 67 ± 3% vs. 43 ± 2%, <i>p</i> < 0.001). MCOPPB also decreased fibrosis and induced angiogenesis. Thus, the ORL1 activator, MCOPPB, may be a novel treatment for preventing HF progression.https://www.mdpi.com/2308-3425/11/11/355prevention of ischemic heart failure progressionORL1 receptor activationMCOPPB |
| spellingShingle | Saliha S. Pathan Aarthi Pugazenthi Beverly R. E. A. Dixon Theodore G. Wensel Todd K. Rosengart Megumi Mathison Activation of a GPCR, ORL1 Receptor: A Novel Therapy to Prevent Heart Failure Progression Journal of Cardiovascular Development and Disease prevention of ischemic heart failure progression ORL1 receptor activation MCOPPB |
| title | Activation of a GPCR, ORL1 Receptor: A Novel Therapy to Prevent Heart Failure Progression |
| title_full | Activation of a GPCR, ORL1 Receptor: A Novel Therapy to Prevent Heart Failure Progression |
| title_fullStr | Activation of a GPCR, ORL1 Receptor: A Novel Therapy to Prevent Heart Failure Progression |
| title_full_unstemmed | Activation of a GPCR, ORL1 Receptor: A Novel Therapy to Prevent Heart Failure Progression |
| title_short | Activation of a GPCR, ORL1 Receptor: A Novel Therapy to Prevent Heart Failure Progression |
| title_sort | activation of a gpcr orl1 receptor a novel therapy to prevent heart failure progression |
| topic | prevention of ischemic heart failure progression ORL1 receptor activation MCOPPB |
| url | https://www.mdpi.com/2308-3425/11/11/355 |
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