Nicotinamide Riboside Alleviates Cardiac Dysfunction and Remodeling in Pressure Overload Cardiac Hypertrophy.
Nicotinamide Riboside Alleviates Cardiac Dysfunction and Remodeling in Pressure Overload Cardiac Hypertrophy.
复制标题
烟酰胺核苷可减轻压力超负荷心脏肥大中的心脏功能障碍和重塑
DOI：
10.1155/2021/5546867
复制
发表时间：
2021
影响因子：
--
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Ma S;Feng J;Lin X;Liu J;Tang Y;Nie S;Gong J;Wang L
心脏肥厚是对压力过载的代偿反应，最终导致心力衰竭。本研究探讨了NAD+促进剂烟酰胺核苷（nicotinamide riboside， NR）对心肌肥厚发生的保护作用，并揭示了其潜在机制的细节。方法采用主动脉横缩术（TAC）建立大鼠心肌肥大模型。小鼠随机分为4组：sham、TAC、sham+NR、TAC+NR。每日口服灌胃给予NR治疗。采用小动物超声心动图评估心脏结构和功能。采用双氢乙啶（DHE）染色、丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性评价线粒体氧化应激。采用实时荧光定量PCR和酶联免疫吸附法检测大鼠心房钠肽（ANP）、脑钠肽（BNP）、IL-1β、TNF-α、Sirtuin3的表达水平。Western blot检测Caspase-1、Caspase-1 pro、cleaved Gasdermin D （GSDMD）、NLRP3、ASC、Sirtuin3、ac-MnSOD、总MnSOD的表达水平。结果TAC组大鼠心/体质量比（HW/BW）、肺/体质量比（LW/BW）及ANP、BNP、LDH水平均明显降低（P < 0.05）。此外，超声心动图数据显示，NR治疗可改善TAC引起的心功能障碍和结构改变（P < 0.05）。NR治疗还降低了炎症因子、IL-1β和TNF-α的水平，并减弱了TAC诱导的NLRP3炎症小体的活化。此外，DHE染色、MDA含量和SOD活性的变化表明NR处理减轻了TAC引起的氧化应激。ELISA和Western blots数据显示，NR处理后心肌NAD+含量和Sirtuin3活性升高，MnSOD乙酰化降低，揭示了潜在信号通路的各个方面。结论NR治疗可减轻tac诱导的病理性心肌肥厚和功能障碍。机械上，这些有益作用归因于通过调节NAD+-Sirtuin3-MnSOD信号通路抑制NLRP3炎性体激活和心肌炎症反应。
Background 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. Methods 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-1β, TNF-α, 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. Results 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 (P < 0.05). Moreover, echocardiography data showed that cardiac dysfunction and structural changes caused by TAC were improved by NR treatment (P < 0.05). NR treatment also reduced levels of the inflammatory cytokines, IL-1β and TNF-α, 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. Conclusion 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.
登录
查看更多内容
影响因子：
37.8
作者：
Diguet N;Trammell SAJ;Tannous C;Deloux R;Piquereau J;Mougenot N;Gouge A;Gressette M;Manoury B;Blanc J;Breton M;Decaux JF;Lavery GG;Baczkó I;Zoll J;Garnier A;Li Z;Brenner C;Mericskay M
通讯作者：
Mericskay M
影响因子：
24
作者：
Sano S;Oshima K;Wang Y;MacLauchlan S;Katanasaka Y;Sano M;Zuriaga MA;Yoshiyama M;Goukassian D;Cooper MA;Fuster JJ;Walsh K
通讯作者：
Walsh K
白介素-1和炎性体作为心血管疾病的治疗靶标。
影响因子：
20.1
作者：
Abbate A;Toldo S;Marchetti C;Kron J;Van Tassell BW;Dinarello CA
通讯作者：
Dinarello CA
白藜芦醇激活SIRT1通过糖尿病心肌病小鼠的线粒体调节来减轻心脏功能障碍。
影响因子：
--
作者：
Ma S;Feng J;Zhang R;Chen J;Han D;Li X;Yang B;Li X;Fan M;Li C;Tian Z;Wang Y;Cao F
通讯作者：
Cao F
LKB1IP 通过靶向 PTEN/Akt 信号通路促进病理性心脏肥大。
影响因子：
5.3
作者：
Tian M;Jiang X;Li X;Yang J;Zhang C;Zhang W
通讯作者：
Zhang W