Abstract P2001: Nicotinamide Riboside the New Promising Drug of Myocardial Infarction Management
| العنوان: | Abstract P2001: Nicotinamide Riboside the New Promising Drug of Myocardial Infarction Management |
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| المؤلفون: | Rana Ghali, Abdo Jurjus, Mathias Mericskay, Nada J Habeichi, Fouad A. Zouein, Marwan M. Refaat, Cynthia Tannous |
| المصدر: | Hypertension. 74 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Drug, biology, business.industry, media_common.quotation_subject, Metabolism, Pharmacology, medicine.disease, Cofactor, chemistry.chemical_compound, chemistry, Fibrosis, Nicotinamide riboside, Internal Medicine, biology.protein, Medicine, NAD+ kinase, Myocardial infarction, business, media_common, Cause of death |
| الوصف: | Introduction: Myocardial infarction (MI) is the major cause of death worldwide. Nicotinamide-Adenine-Dinucleotide (NAD) is emerging as a metabolic target being a major coenzyme in mitochondrial oxidation and oxidative phosphorylation and a substrate of Sirtuins and PARPs, critical enzymes for cardiac remodeling. Altered NAD homeostasis is reported in several models of heart failure including MI with a striking upregulation of Nicotinamide-Riboside-Kinase2 (NMRK2) and a decrease of NAD levels. NMRK2 requires Nicotinamide Riboside (NR) as a substrate to produce NAD. In this study, we hypothesized that stimulating NMRK2 pathway by NR supplementation will upregulate NAD synthesis and subsequently improve metabolic state and cardiac function post-MI. Methods: MI was induced by the left anterior descending coronary artery ligation in 2-3 months old male mice. Echocardiography was performed at baseline, day 1, and day 4 following MI. At sacrifice, cardiac genes expression was evaluated by RT-qPCR and myocardial NAD levels were determined using a colorimetric assay. Histologically, Masson-Trichrome was performed on cardiac sections to assess cardiac fibrosis. Results: RT-qPCR analysis showed a 60 fold increase of Nmrk2 expression levels (P&it0.01) 4 days following MI. This upregulation was highlighted by the boost of NAD levels (708.81±79.83 pmoles/g of tissue in the MI-NR group vs 394.12 ±84.04 pmoles/g of tissue in the control group (p&it0.05)). Following MI, mitochondrial SIRT3 expression dropped by 40% and NR restored those levels which are critical for mitochondrial biogenesis. NR treatment markedly decreased the expression of PARP1 (1.22±0.34 in MI-NR group vs 2.69±0.45 in MI group (p&it0.05)), a well-known consumer of NAD. Histologically, fibrosis levels significantly dropped 4 days following NR treatment when compared to non-treated MI group (11±2,72 u.a vs 18±1,98 u.a, p&it0.05). Conclusion: NR treatment improves myocardial metabolic impairment, but not myocardial function, as early as 4 days following MI when compared to relative control groups. Additional experiments are underway to reveal the impact of NR treatment on cardiac remodeling and function at 7 days post-MI. |
| تدمد: | 1524-4563 0194-911X |
| DOI: | 10.1161/hyp.74.suppl_1.p2001 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::7beec53fb7156b01caac7315aa74d28d https://doi.org/10.1161/hyp.74.suppl_1.p2001 |
| رقم الانضمام: | edsair.doi...........7beec53fb7156b01caac7315aa74d28d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244563 0194911X |
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| DOI: | 10.1161/hyp.74.suppl_1.p2001 |