Astaxanthin attenuated pressure overload-induced cardiac dysfunction and myocardial fibrosis: Partially by activating SIRT1
Astaxanthin attenuated pressure overload-induced cardiac dysfunction and myocardial fibrosis: Partially by activating SIRT1
复制标题
虾青素减轻压力超负荷引起的心脏功能障碍和心肌纤维化：部分通过激活 SIRT1
DOI：
10.1016/j.bbagen.2017.03.007
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发表时间：
2017
影响因子：
3
通讯作者：
Gao Hai Qing
中科院分区：
文献类型：
--
作者：
Zhang Jun;Wang Quan Zhen;Zhao Shao Hua;Ji Xiang;Qiu Jie;Wang Jian;Zhou Yi;Cai Qian;Zhang Jie;Gao Hai Qing
背景心肌纤维化是心功能不全的重要原因。虾青素（AST），类胡萝卜素家族的一员，是一个众所周知的抗氧化剂，但其影响和潜在的机制在心肌fibrosis.MethodsIn体内，心肌纤维化和心功能不全，诱导使用横向主动脉缩窄（TAC）。术后给予AST 12周，体外用转化生长因子β 1（transforming growth factor β 1，TGF-β 1）刺激人心脏成纤维细胞（human cardiac fibroblasts，HCF）。分别用EX-527（6-chloro-2，3，4，9-tetrahydro-1H-carbazole-1-carboxamide）和SIRT 1 siRNA在体内和体外抑制SIRT 1。测定AST对心功能和纤维化的影响。SIRT1的表达和活性进行了测定，以探讨其影响的机制。受体激活的SMADs（R-SMADs），包括SMAD2和SMAD3，在这些过程中发挥了重要作用。AST可抑制TAC手术诱导的磷酸化和乙酰化R-SMADs表达的增加，抑制R-SMADs的转位和转录活性。这些作用伴随着SIRT1表达和活性的增加。抑制SIRT1衰减的乙酰化和转录活性的R-SMADs，但不是他们的磷酸化和translocation.ConclusionsOur数据表明，AST改善心脏功能，并通过减少磷酸化和去乙酰化的R-SMADs减弱纤维化。SIRT 1通过减少R-SMADs的乙酰化而有助于AST的保护功能。一般意义这些数据表明，AST可用作心功能不全和心肌纤维化的预防/治疗剂。
BackgroundMyocardial fibrosis contributes to cardiac dysfunction. Astaxanthin (AST), a member of the carotenoid family, is a well-known antioxidant, but its effect on and underlying mechanisms in myocardial fibrosis are poorly understood.MethodsIn vivo, myocardial fibrosis and cardiac dysfunction were induced using transverse aortic constriction (TAC). AST was administered to mice for 12 weeks post-surgery.In vitro, transforming growth factor β1 (TGF-β1) was used to stimulate human cardiac fibroblasts (HCFs). EX-527 (6-chloro-2, 3, 4, 9-tetrahydro-1H-carbazole-1-carboxamide) and SIRT1 siRNA were used to inhibit SIRT1in vivoandin vitro, respectively. The effects of AST on cardiac function and fibrosis were determined. SIRT1 expression and activity were measured to explore the mechanisms underlying its effects.ResultsAST improved cardiac function and attenuated fibrosis. Receptor activated-SMADs (R-SMADs), including SMAD2 and SMAD3, played important roles in these processes. The TAC surgery-induced increases in the expression of phosphorylated and acetylated R-SMADs were attenuated by treatment with AST, the translocation and transcriptional activity of R-SMADs were also restrained. These effects were accompanied by an increase in the expression and activity of SIRT1. Inhibiting SIRT1 attenuated the acetylation and transcriptional activity of R-SMADs, but not their phosphorylation and translocation.ConclusionsOur data demonstrate that AST improves cardiac function and attenuates fibrosis by decreasing phosphorylation and deacetylation of R-SMADs. SIRT1 contributes to AST’s protective function by reducing acetylation of R-SMADs.General significanceThese data suggest that AST may be useful as a preventive/therapeutic agent for cardiac dysfunction and myocardial fibrosis.