Nicotinamide Riboside the new promising drug for Myocardial Infarction Management

الموضوعات

طب

الملخص

Nicotinamide Adenine Dinucleotide (NAD) is a vital cofactor for fuel oxidation and oxidative phosphorylation. The cellular levels of NAD are critical regulators of metabolism and bioenergetics that link cellular energy status to a wide variety of processes which regulate cell survival. In the context of myocardial infarction (MI), NAD homeostasis is altered, and cellular hypertrophy occurs in response to increased burden of stress and needs. Nicotinamide-Riboside-Kinase2 (NMRK2) is an enzyme involved in NAD salvage pathway. Based on preliminary evidence, NMRK2 which requires an exogenous B3 vitamin (Nicotinamide Riboside (NR)) supplementation to synthesize NAD, is highly upregulated following MI. 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. MI was induced by the left anterior descending coronary artery ligation in 2-3 months old male mice. Mice were treated with NR (1 µmole/g of body weight) or vehicle (PBS) and sacrificed on day 4 and day 7 following MI. Western Blot preliminary analysis showed that following MI, SIRT3 expression level, which is important for mitochondrial biogenesis, was decreased and PARP1 expression, which depletes myocardial NAD when over activated, was increased following MI. NR supplementation was able to bring the expression level of those NAD consuming enzymes back to normal and preventing their detrimental effects on the heart. Metabolically, NAD levels were significantly increased in the MI group treated with NR, when compared to controls, confirming the upregulation of NMRK2. Furthermore, NR treatment decreased the expression of inflammatory markers (IL-1β and IL-4). Histological preliminary findings revealed a significant drop in fibrosis 4 days following NR treatment when compared to non-treated MI group (11% vs. 18%, p<0.05). Additionally, left ventricular cardiomyocytes cross-sectional area at the level of the pericardium and the myocardium decreased 4 days following NR injection which reflects an inhibition of cardiomyocytes hypertrophy in the non-infarcted area. In conclusion, our preliminary data show that NR treatment could improve cardiac remodeling at the molecular, metabolic and histological levels post-MI. Additional experiments are currently underway to strengthen our findings and to further elaborate on the impact of NR treatment on cardiac remodeling and function.

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التعريف والنوع

رقم الوثيقة

0b6ee333-5284-470f-b522-84823e87671e

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل ماجيستير

نوع الملف

pdf text

أسماء الملفات

797328_1.pdf

بيانات النشر

ألقاب المؤلفين

[{"name_ar":"Fouad Zouein","title_ar":"اشراف","title_en":"Supervision"},{"name_ar":"Sara Adnan Alkassas","title_ar":"اعداد","title_en":"Preparation"}]

اللغة

English

المصدر والدورية

اسم المصدر

Nicotinamide Riboside the new promising drug for Myocardial Infarction Management

المحتوى والصفحات

عدد الصفحات

0

إشراف وإعداد

الإشراف

Fouad Zouein

الإعداد

Sara Adnan Alkassas

الاقتباسات الببليوغرافية