Nicotinamide mononucleotide attenuates isoproterenol-induced cardiac fibrosis by regulating oxidative stress and Smad3 acetylation

被引:41
作者
Wu, Keke [1 ]
Li, Biao [1 ]
Lin, Qiuzhen [1 ]
Xu, Wanghan [3 ]
Zuo, Wanyun [1 ]
Li, Jiayi [1 ]
Liu, Na [1 ]
Tu, Tao [1 ]
Zhang, Baojian [1 ,2 ]
Xiao, Yichao [1 ]
Liu, Qiming [1 ]
机构
[1] Cent South Univ, Xiangya Hosp 2, Dept Cardiovasc Med, Changsha, Hunan, Peoples R China
[2] Xinjiang Med Univ, Dept Cardiol, Affiliated Chinese Med Hosp, Urumqi City, Xinjiang Provin, Peoples R China
[3] Cent South Univ, Xiangya Hosp 2, Dept Stomatol, Changsha, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
Cardiac fibrosis; Nicotinamide mononucleotide; Oxidative stress; Acetylation; Smad signaling; HIGH-FAT DIET; MYOCARDIAL FIBROSIS; RENAL FIBROSIS; TGF-BETA; NAD(+); SIRT1; ACTIVATION; HEART; FIBROBLAST; PROTECTS;
D O I
10.1016/j.lfs.2021.119299
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Aims: Cardiac fibrosis is a pathological hallmark of progressive heart diseases currently lacking effective treatment. Nicotinamide mononucleotide (NMN), a member of the vitamin B3 family, is a defined biosynthetic precursor of nicotinamide adenine dinucleotide (NAD(+)). Its beneficial effects on cardiac diseases are known, but its effects on cardiac fibrosis and the underlying mechanism remain unclear. We aimed to elucidate the protective effect of NMN against cardiac fibrosis and its underlying mechanisms of action. Materials and methods: Cardiac fibrosis was induced by isoproterenol (ISO) in mice. NMN was administered by intraperitoneal injection. In vitro, cardiac fibroblasts (CFs) were stimulated by transforming growth factor-beta (TGF-beta) with or without NMN and sirtinol, a SIRT1 inhibitor. Levels of cardiac fibrosis, NAD(+)/SIRT1 alteration, oxidative stress, and Smad3 acetylation were evaluated by real-time polymerase chain reaction, western blots, immunohistochemistry staining, immunoprecipitation, and assay kits. Key findings: ISO treatment induced cardiac dysfunction, fibrosis, and hypertrophy in vivo, whereas NMN alleviated these changes. Additionally, NMN suppressed CFs activation stimulated by TGF-beta in vitro. Mechanistically, NMN restored the NAD(+)/SIRT1 axis and inhibited the oxidative stress and Smad3 acetylation induced by ISO or TGF-beta. However, the protective effects of NMN were partly antagonized by sirtinol in vitro. Significance: NMN could attenuate cardiac fibrosis in vivo and fibroblast activation in vitro by suppressing oxidative stress and Smad3 acetylation in a NAD(+)/SIRT1-dependent manner.
引用
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页数:12
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共 55 条
[41]   Sirt1 acts in association with PPARα to protect the heart from hypertrophy, metabolic dysregulation, and inflammation [J].
Planavila, Ana ;
Iglesias, Roser ;
Giralt, Marta ;
Villarroya, Francesc .
CARDIOVASCULAR RESEARCH, 2011, 90 (02) :276-284
[42]   MOLECULAR CHARACTERIZATION OF ANGIOTENSIN-II-INDUCED HYPERTROPHY OF CARDIAC MYOCYTES AND HYPERPLASIA OF CARDIAC FIBROBLASTS - CRITICAL ROLE OF THE AT(1) RECEPTOR SUBTYPE [J].
SADOSHIMA, J ;
IZUMO, S .
CIRCULATION RESEARCH, 1993, 73 (03) :413-423
[43]   A High-Fat Diet and NAD+ Activate Sirt1 to Rescue Premature Aging in Cockayne Syndrome [J].
Scheibye-Knudsen, Morten ;
Mitchell, Sarah J. ;
Fang, Evandro F. ;
Iyama, Teruaki ;
Ward, Theresa ;
Wang, James ;
Dunn, Christopher A. ;
Singh, Nagendra ;
Veith, Sebastian ;
Hasan-Olive, Md Mahdi ;
Mangerich, Aswin ;
Wilson, Mark A. ;
Mattson, Mark P. ;
Bergersen, Linda H. ;
Cogger, Victoria C. ;
Warren, Alessandra ;
Le Couteur, David G. ;
Moaddel, Ruin ;
Wilson, David M., III ;
Croteau, Deborah L. ;
de Cabo, Rafael ;
Bohr, Vilhelm A. .
CELL METABOLISM, 2014, 20 (05) :840-855
[44]   The DNA binding activities of Smad2 and Smad3 are regulated by coactivator-mediated acetylation [J].
Simonsson, Maria ;
Kanduri, Meena ;
Gronroos, Eva ;
Heldin, Carl-Henrik ;
Ericsson, Johan .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (52) :39870-39880
[45]   Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction [J].
Someya, Shinichi ;
Yu, Wei ;
Hallows, William C. ;
Xu, Jinze ;
Vann, James M. ;
Leeuwenburgh, Christiaan ;
Tanokura, Masaru ;
Denu, John M. ;
Prolla, Tomas A. .
CELL, 2010, 143 (05) :802-812
[46]   Cardiac Fibroblast The Renaissance Cell [J].
Souders, Colby A. ;
Bowers, Stephanie L. K. ;
Baudino, Troy A. .
CIRCULATION RESEARCH, 2009, 105 (12) :1164-1176
[47]   Cardiac fibroblasts are essential for the adaptive response of the murine heart to pressure overload [J].
Takeda, Norifumi ;
Manabe, Ichiro ;
Uchino, Yuichi ;
Eguchi, Kosei ;
Matsumoto, Sahohime ;
Nishimura, Satoshi ;
Shindo, Takayuki ;
Sano, Motoaki ;
Otsu, Kinya ;
Snider, Paige ;
Conway, Simon J. ;
Nagai, Ryozo .
JOURNAL OF CLINICAL INVESTIGATION, 2010, 120 (01) :254-265
[48]   Cardiac Fibrosis The Fibroblast Awakens [J].
Travers, Joshua G. ;
Kamal, Fadia A. ;
Robbins, Jeffrey ;
Yutzey, Katherine E. ;
Blaxall, Burns C. .
CIRCULATION RESEARCH, 2016, 118 (06) :1021-1040
[49]   PARP-1 inhibition protects the diabetic heart through activation of SIRT1-PGC-1α axis [J].
Waldman, Maayan ;
Nudelman, Vadim ;
Shainberg, Asher ;
Abraham, Nader G. ;
Komwoski, Ran ;
Aravot, Dan ;
Arad, Michael ;
Hochhauser, Edith .
EXPERIMENTAL CELL RESEARCH, 2018, 373 (1-2) :112-118
[50]   Imatinib attenuates cardiac fibrosis by inhibiting platelet-derived growth factor receptors activation in isoproterenol induced model [J].
Wang, Le-Xun ;
Yang, Xiao ;
Yue, Yuan ;
Fan, Tian ;
Hou, Jian ;
Chen, Guang-Xian ;
Liang, Meng-Ya ;
Wu, Zhong-Kai .
PLOS ONE, 2017, 12 (06)