CD38 promotes angiotensin II-induced cardiac hypertrophy.
CD38 promotes angiotensin II-induced cardiac hypertrophy.
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CD38促进血管紧张素II诱导的心脏肥大
DOI：
10.1111/jcmm.13076
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发表时间：
2017-08
影响因子：
5.3
通讯作者：
Xin HB
中科院分区：
文献类型：
--
作者：
Guan XH;Hong X;Zhao N;Liu XH;Xiao YF;Chen TT;Deng LB;Wang XL;Wang JB;Ji GJ;Fu M;Deng KY;Xin HB
心脏肥大是心力衰竭临床过程中的早期标志，并受到多种信号通路的调节。最近，我们观察到来自 CD38 敲除小鼠的小鼠胚胎成纤维细胞对氧化应激（例如 H2O2 诱导的损伤和缺氧/复氧诱导的损伤）具有显着的抵抗力。此外，我们还发现CD38敲除小鼠通过激活SIRT1/FOXOs介导的抗氧化应激途径保护心脏免受缺血再灌注损伤。然而，CD38 在心脏肥大中的作用尚未探讨。在这里，我们研究了 CD38 在血管紧张素 II (Ang-II) 诱导的心脏肥大中的作用和机制。通过微型渗透泵输注 Ang-II 14 天后，CD38 敲除小鼠和野生型小鼠均产生了类似的高血压。然而，与 CD38 敲除小鼠相比，野生型小鼠的心脏肥大和纤维化要严重得多。一致地，RNAi诱导的CD38敲除降低了Ang-II刺激的H9c2细胞中心房钠尿因子（ANF）和脑钠尿肽（BNP）的基因表达以及活性氧的产生。此外，在CD38敲低的H9c2细胞中SIRT3的表达升高，其中SIRT3可能进一步激活FOXO3抗氧化途径。 CD38敲低的H9c2细胞中Ang-II诱导的细胞内Ca2+释放显着减少，这可能与NFATc4核转位减少和ERK/AKT磷酸化抑制有关。我们得出结论，CD38可能通过抑制SIRT3表达和激活Ca2+-NFAT信号通路在心脏肥大中发挥重要作用。因此，CD38可能是治疗心脏肥大的新靶点。
Cardiac hypertrophy is an early hallmark during the clinical course of heart failure and regulated by various signalling pathways. Recently, we observed that mouse embryonic fibroblasts from CD38 knockout mice were significantly resistant to oxidative stress such as H2O2‐induced injury and hypoxia/reoxygenation‐induced injury. In addition, we also found that CD38 knockout mice protected heart from ischaemia reperfusion injury through activating SIRT1/FOXOs‐mediated antioxidative stress pathway. However, the role of CD38 in cardiac hypertrophy is not explored. Here, we investigated the roles and mechanisms of CD38 in angiotensin II (Ang‐II)‐induced cardiac hypertrophy. Following 14 days of Ang‐II infusion with osmotic mini‐pumps, a comparable hypertension was generated in both of CD38 knockout and wild‐type mice. However, the cardiac hypertrophy and fibrosis were much more severe in wild‐type mice compared with CD38 knockout mice. Consistently, RNAi‐induced knockdown of CD38 decreased the gene expressions of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) and reactive oxygen species generation in Ang‐II‐stimulated H9c2 cells. In addition, the expression of SIRT3 was elevated in CD38 knockdown H9c2 cells, in which SIRT3 may further activate the FOXO3 antioxidant pathway. The intracellular Ca2+ release induced by Ang‐II markedly decreased in CD38 knockdown H9c2 cells, which might be associated with the decrease of nuclear translocation of NFATc4 and inhibition of ERK/AKT phosphorylation. We concluded that CD38 plays an essential role in cardiac hypertrophy probably via inhibition of SIRT3 expression and activation of Ca2+‐NFAT signalling pathway. Thus, CD38 may be a novel target for treating cardiac hypertrophy.
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DOI：
10.1152/ajprenal.00372.2004
发表时间：
2005-04-01
影响因子：
4.2
作者：
Fellner, SK;Arendshorst, WJ
通讯作者：
Arendshorst, WJ
影响因子：
7.8
作者：
Haq, S;Choukroun, G;Kang, Z B;Ranu, H;Matsui, T;Rosenzweig, A;Molkentin, J D;Alessandrini, A;Woodgett, J;Hajjar, R;Michael, A;Force, T
通讯作者：
Force, T
影响因子：
3.7
作者：
Gul R;Park DR;Shawl AI;Im SY;Nam TS;Lee SH;Ko JK;Jang KY;Kim D;Kim UH
通讯作者：
Kim UH
CD38 缺乏通过激活 SIRT1/FOXO 介导的抗氧化应激途径保护心脏免受缺血/再灌注损伤。
影响因子：
--
作者：
Guan XH;Liu XH;Hong X;Zhao N;Xiao YF;Wang LF;Tang L;Jiang K;Qian YS;Deng KY;Ji G;Fu M;Xin HB
通讯作者：
Xin HB
影响因子：
4.8
作者：
Chandrasekar, B;Mummidi, S;Nemer, M
通讯作者：
Nemer, M