| DOI | 10.1073/pnas.2019835118
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| Growth hormone-releasing hormone agonists ameliorate chronic kidney disease-induced heart failure with preserved ejection fraction |
| Rieger A.C.; Bagno L.L.; Salerno A.; Florea V.; Rodriguez J.; Rosado M.; Turner D.; Dulce R.A.; Takeuchi L.M.; Kanashiro-Takeuchi R.M.; Buchwald P.; Wanschel A.C.B.A.; Balkan W.; Schulman I.H.; Schally A.V.; Hare J.M.
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| 发表日期 | 2021
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| ISSN | 00278424
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| 卷号 | 118期号:4 |
| 英文摘要 | Therapies for heart failure with preserved ejection fraction (HFpEF) are lacking. Growth hormone-releasing hormone agonists (GHRH-As) have salutary effects in ischemic and nonischemic heart failure animal models. Accordingly, we hypothesized that GHRH-A treatment ameliorates chronic kidney disease (CKD)-induced HFpEF in a large-animal model. Female Yorkshire pigs (n = 16) underwent 5/6 nephrectomy via renal artery embolization and 12 wk later were randomized to receive daily subcutaneous injections of GHRH-A (MR-409; n = 8; 30 μg/kg) or placebo (n = 8) for 4 to 6 wk. Renal and cardiac structure and function were serially assessed postembolization. Animals with 5/6 nephrectomy exhibited CKD (elevated blood urea nitrogen [BUN] and creatinine) and faithfully recapitulated the hemodynamic features of HFpEF. HFpEF was demonstrated at 12 wk by maintenance of ejection fraction associated with increased left ventricular mass, relative wall thickness, end-diastolic pressure (EDP), end-diastolic pressure/end-diastolic volume (EDP/EDV) ratio, and tau, the time constant of isovolumic diastolic relaxation. After 4 to 6 wk of treatment, the GHRH-A group exhibited normalization of EDP (P = 0.03), reduced EDP/EDV ratio (P = 0.018), and a reduction in myocardial pro-brain natriuretic peptide protein abundance. GHRH-A increased cardiomyocyte [Ca2+] transient amplitude (P = 0.009). Improvement of the diastolic function was also evidenced by increased abundance of titin isoforms and their ratio (P = 0.0022). GHRH-A exerted a beneficial effect on diastolic function in a CKD large-animal model as demonstrated by improving hemodynamic, structural, and molecular characteristics of HFpEF. These findings have important therapeutic implications for the HFpEF syndrome. © 2021 National Academy of Sciences. All rights reserved. |
| 英文关键词 | Cardiorenal syndrome; Chronic kidney disease; Ejection fraction; Heart failure with preserved; Large animal model |
| 语种 | 英语
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| 来源期刊 | Proceedings of the National Academy of Sciences of the United States of America
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| 文献类型 | 期刊论文
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| 条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/180862
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| 作者单位 | Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL 33136, United States; Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, United States; Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, United States; Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, United States; Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, FL 33136, United States; Endocrine, Polypeptide and Cancer Institute, Veteran Affairs Medical Center, Miami, FL 33125, United States
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推荐引用方式
GB/T 7714 |
Rieger A.C.,Bagno L.L.,Salerno A.,et al. Growth hormone-releasing hormone agonists ameliorate chronic kidney disease-induced heart failure with preserved ejection fraction[J],2021,118(4).
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| APA |
Rieger A.C..,Bagno L.L..,Salerno A..,Florea V..,Rodriguez J..,...&Hare J.M..(2021).Growth hormone-releasing hormone agonists ameliorate chronic kidney disease-induced heart failure with preserved ejection fraction.Proceedings of the National Academy of Sciences of the United States of America,118(4).
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| MLA |
Rieger A.C.,et al."Growth hormone-releasing hormone agonists ameliorate chronic kidney disease-induced heart failure with preserved ejection fraction".Proceedings of the National Academy of Sciences of the United States of America 118.4(2021).
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