Department of Cardiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China 210002.
Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China 210002.
Oxid Med Cell Longev. 2021 Sep 15;2021:5546867. doi: 10.1155/2021/5546867. eCollection 2021.
Cardiac hypertrophy is a compensatory response to pressure overload, which eventually leads to heart failure. The current study explored the protective effect of nicotinamide riboside (NR), a NAD booster that may be administered through the diet, on the occurrence of myocardial hypertrophy and revealed details of its underlying mechanism.
Transverse aortic constriction (TAC) surgery was performed to establish a murine model of myocardial hypertrophy. Mice were randomly divided into four groups: sham, TAC, sham+NR, and TAC+NR. NR treatment was given daily by oral gavage. Cardiac structure and function were assessed using small animal echocardiography. Mitochondrial oxidative stress was evaluated by dihydroethidium (DHE) staining, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity. Levels of expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), IL-1, TNF-, and Sirtuin3 were measured by real-time PCR and ELISA. Expression levels of Caspase-1, Caspase-1 pro, cleaved Gasdermin D (GSDMD), NLRP3, ASC, Sirtuin3, ac-MnSOD, and total MnSOD were measured by Western blot.
Reductions in the heart/body mass ratio (HW/BW) and lung/body mass ratio (LW/BW) and in ANP, BNP, and LDH levels were observed in the TAC group on the administration of NR ( < 0.05). Moreover, echocardiography data showed that cardiac dysfunction and structural changes caused by TAC were improved by NR treatment ( < 0.05). NR treatment also reduced levels of the inflammatory cytokines, IL-1 and TNF-, and attenuated activation of NLRP3 inflammasomes induced by TAC. Furthermore, changes in DHE staining, MDA content, and SOD activity indicated that NR treatment alleviated the oxidative stress caused by TAC. Data from ELISA and Western blots revealed elevated myocardial NAD content and Sirtuin3 activity and decreased acetylation of MnSOD after NR treatment, exposing aspects of the underlying signaling pathway.
NR treatment alleviated TAC-induced pathological cardiac hypertrophy and dysfunction. Mechanically, these beneficial effects were attributed to the inhibition of NLRP3 inflammasome activation and myocardial inflammatory response by regulating the NAD-Sirtuin3-MnSOD signaling pathway.
心肌肥厚是压力超负荷的代偿反应，最终会导致心力衰竭。本研究探讨了烟酰胺核糖（NR）的保护作用，NR 是一种 NAD 增强剂，可能通过饮食摄入，它可预防心肌肥厚的发生，并揭示了其潜在机制的细节。
通过横主动脉缩窄（TAC）手术建立心肌肥厚的小鼠模型。将小鼠随机分为 4 组：假手术组、TAC 组、假手术+NR 组和 TAC+NR 组。通过口服灌胃给予 NR 治疗。使用小动物超声心动图评估心脏结构和功能。通过二氢乙啶（DHE）染色、丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性评估线粒体氧化应激。通过实时 PCR 和 ELISA 测量心房利钠肽（ANP）、脑利钠肽（BNP）、IL-1、TNF-和 Sirtuin3 的表达水平。通过 Western blot 测量 Caspase-1、Caspase-1 pro、cleaved Gasdermin D（GSDMD）、NLRP3、ASC、Sirtuin3、ac-MnSOD 和总 MnSOD 的表达水平。
NR 给药可降低 TAC 组的心脏/体重比（HW/BW）和肺/体重比（LW/BW）以及 ANP、BNP 和 LDH 水平（<0.05）。此外，NR 治疗改善了 TAC 引起的心脏功能障碍和结构改变（<0.05）。NR 治疗还降低了炎症细胞因子 IL-1 和 TNF-的水平，并减轻了 TAC 诱导的 NLRP3 炎性小体的激活。此外，DHE 染色、MDA 含量和 SOD 活性的变化表明，NR 治疗减轻了 TAC 引起的氧化应激。ELISA 和 Western blot 的数据显示，NR 治疗后心肌 NAD 含量和 Sirtuin3 活性升高，MnSOD 乙酰化降低，揭示了潜在的信号通路。
NR 治疗减轻了 TAC 诱导的病理性心肌肥厚和功能障碍。从机制上讲，这些有益作用归因于通过调节 NAD-Sirtuin3-MnSOD 信号通路抑制 NLRP3 炎性小体的激活和心肌炎症反应。
