## 2 Effects of Nicotinamide Riboside on Several Organs and Systems
### Nicotinamide Riboside and the Cardiovascular System  
Dietary supplementation by NAD\({}^{+}\) precursors (e.g., NR) appears to have a useful impact in many areas of cardiovascular diseases (CVDs). Here, the goal is to improve overall cardiometabolic health by increasing OXPHOS capacity and mitophagy, removing mitochondrial deoxyribonucleic acid (mtDNA) mutations, and for cardioprotective effects in ischemia-reperfusion (I-R) injury, arrhythmias, heart failure (HF), myocardial infarction (MI), and high blood pressure [73; 74; 75; 76]. For example, in an experimental model of cafeteria (CAF) diet-induced obesity (DIO), oral administration of 400 mg/kg of NR combined with CR (\(-62\%\) kcal) for 28 days decreased the weight of obese male Wistar rats, their visceral and subcutaneous adiposity, their triglyceride (TG)/high-density lipoprotein (HDL) ratio, and their heart size. Also, insulin resistance and antioxidant capacity (glutathione peroxidase (GPx) and CAT enzymatic markers of cardiac OXS) were improved by NRS [77]. In a mouse model, NR treatment for 30 days led to the NAD\({}^{+}\)/NADH ratio balancing, lowering acetylation level, improving MT function and HF with preserved ejection fraction (EF) phenotypes [78]. In a murine model of myocardial hypertrophy induced by transverse aortic constriction (TAC) surgery, NR dietary supplementation reduced levels of inflammatory cytokines (IL-1\(\beta\), TNF-\(\alpha\)), mitigated the NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, the elevation of myocardial NAD\({}^{+}\) level, and the improving of cardiac dysfunctions and morpho-functional changes (myocardial hypertrophy). The research led to the observation that the NAD\({}^{+}\)/SIRT3/manganese superoxide dismutase (MnSOD) signaling pathway was also regulated by NRS [79]. Moreover, in mice, NR administration inhibited TAC-induced endothelial-to-mesenchymal transition of endothelial cells (ECs) and promoted MT unfolded protein response leading to improvement in prohibiting proteins' expression and to the decrease in cardiac fibrosis (CF) progression [80]. Recent clinical trials highlighted the cardioprotective role of oral NRS (usually 1 g twice daily, a well-tolerated dose) for ischemic heart disease patients diagnosed with atrial fibrillation (AF) [81], HF patients with MT dysfunction and peripheral blood mononuclear cells (PBMCs) inflammatory activation [82], or clinically stable HF patients with reduced EF [83]. In murine models, boosting NAD\({}^{+}\) levels using dietary NRS appeared to reduce the development of aortic aneurysms and sudden death by aortic ruptures. Acute aortic aneurysms and lethal ruptures were induced by angiotensin II (Ang II) administration to apolipoprotein E (ApoE)-deficient mice fed throughout the entire experiment with a Western diet (WD). Fatal aortic ruptures caused by atherosclerosis and hypertension are reported to be prevented by boosting MT respiration [84]. Additional studies in this space have accumulated. Thus, NRK2 is reported to limit dilated cardiomyopathyopathy (DCM) in mice with chronic pressure overload (PO). In addition, Ang II-induced cardiomyocyte death is reported to be mitigated by NRK2 overexpression [85]. NR administration preserves cardiac function in a mouse model of DCM and TAC-induced cardiac hypertrophy, alleviating HF development by stabilizing NAD\({}^{+}\) levels in the myocardial tissue. NA adenine dinucleotide, methylnicotinamide (MeNAM), and \(N^{1}\)-methyl-4-pyridone-5-carboxamide represent the three biomarkers with increased myocardial levels due to NRS [86]. In murine models, NR was i.v. administered to assess its ability to mitigate doxorubicin (DOX)-induced cardiomyopathy. OXS, autolysosomes accumulation and autophagic flux blockade because of DOX cardiotoxicity were all prevented by NR via NAD\({}^{+}\)/SIRT1 signaling pathway [87; 88]. For the specific pathogen-free male Wistar rats, the protective effect exhibited significant levels through the preventive use of NR [89]. NR also attenuated cardiac and I-R injury.