Cardiac nuclear high mobility group box 1 prevents the development of cardiac hypertrophy and heart failure.
Cardiac nuclear high mobility group box 1 prevents the development of cardiac hypertrophy and heart failure.
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DOI：
10.1093/cvr/cvt128
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发表时间：
2013-09-01
影响因子：
10.8
通讯作者：
Kubota I
中科院分区：
文献类型：
--
作者：
Funayama A;Shishido T;Netsu S;Narumi T;Kadowaki S;Takahashi H;Miyamoto T;Watanabe T;Woo CH;Abe J;Kuwahara K;Nakao K;Takeishi Y;Kubota I
高迁移率族蛋白1（HMGB 1）是一种丰富的、普遍存在的核DNA结合蛋白，其具有依赖于其细胞位置的多种功能。HMGB 1与DNA结合，促进许多核功能，包括维持基因组稳定性，转录和修复。然而，关于核HMGB 1对心脏肥大和心力衰竭的影响知之甚少。本研究的目的是检查核HMGB 1是否在压力超负荷诱导的心肌肥厚的发展中起作用。通过免疫组织化学分析人类活检样本显示，与正常心脏相比，衰竭心脏的核HMGB 1表达减少。在新生大鼠心肌细胞中，细胞核HMGB 1在内皮素-1（ET-1）和血管紧张素II（Ang II）刺激下均降低，其中细胞核HMGB 1被乙酰化并移位至细胞质。核HMGB 1过表达可减轻ET-1诱导的心肌细胞肥大。在心脏特异性过表达HMGB 1的转基因小鼠（HMGB 1-Tg）和野生型（WT）小鼠中进行胸横主动脉缩窄（TAC）。TAC后HMGB 1-Tg小鼠的心肌肥大减弱，TAC后HMGB 1-Tg小鼠的存活率高于WT小鼠。与WT小鼠相比，HMGB 1-Tg小鼠中胎儿心脏基因的诱导减少。与WT小鼠相比，HMGB 1-Tg小鼠的核HMGB 1表达得以保留，并且在HMGB 1-TG小鼠中减弱TAC后显著减轻DNA损伤。这些结果表明，维持稳定的核HMGB 1水平通过抑制DNA损伤来防止肥大和心力衰竭。
High mobility group box 1 (HMGB1) is an abundant and ubiquitous nuclear DNA-binding protein that has multiple functions dependent on its cellular location. HMGB1 binds to DNA, facilitating numerous nuclear functions including maintenance of genome stability, transcription, and repair. However, little is known about the effects of nuclear HMGB1 on cardiac hypertrophy and heart failure. The aim of this study was to examine whether nuclear HMGB1 plays a role in the development of cardiac hypertrophy induced by pressure overload. Analysis of human biopsy samples by immunohistochemistry showed decreased nuclear HMGB1 expression in failing hearts compared with normal hearts. Nuclear HMGB1 decreased in response to both endothelin-1 (ET-1) and angiotensin II (Ang II) stimulation in neonatal rat cardiomyocytes, where nuclear HMGB1 was acetylated and translocated to the cytoplasm. Overexpression of nuclear HMGB1 attenuated ET-1 induced cardiomyocyte hypertrophy. Thoracic transverse aortic constriction (TAC) was performed in transgenic mice with cardiac-specific overexpression of HMGB1 (HMGB1-Tg) and wild-type (WT) mice. Cardiac hypertrophy after TAC was attenuated in HMGB1-Tg mice and the survival rate after TAC was higher in HMGB1-Tg mice than in WT mice. Induction of foetal cardiac genes was decreased in HMGB1-Tg mice compared with WT mice. Nuclear HMGB1 expression was preserved in HMGB1-Tg mice compared with WT mice and significantly attenuated DNA damage after TAC was attenuated in HMGB1-TG mice. These results suggest that the maintenance of stable nuclear HMGB1 levels prevents hypertrophy and heart failure by inhibiting DNA damage.
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影响因子：
30.8
作者：
Calogero, S;Grassi, F;Bianchi, ME
通讯作者：
Bianchi, ME
影响因子：
11.1
作者：
Andrassy, M.;Volz, H. C.;Korosoglou, G.
通讯作者：
Korosoglou, G.
影响因子：
64.8
作者：
Scaffidi, P;Misteli, T;Bianchi, ME
通讯作者：
Bianchi, ME
影响因子：
5.3
作者：
El Gazzar, Mohamed;Yoza, Barbara K.;McCall, Charles E.
通讯作者：
McCall, Charles E.
影响因子：
6.7
作者：
El Gazzar, M.
通讯作者：
El Gazzar, M.