β3-Adrenoreceptor stimulation protects against myocardial infarction injury via eNOS and nNOS activation.
β3-Adrenoreceptor stimulation protects against myocardial infarction injury via eNOS and nNOS activation.
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β3-肾上腺素受体刺激通过 eNOS 和 nNOS 激活防止心肌梗死损伤
DOI：
10.1371/journal.pone.0098713
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zheng Q
中科院分区：
文献类型：
--
作者：
Niu X;Zhao L;Li X;Xue Y;Wang B;Lv Z;Chen J;Sun D;Zheng Q
一氧化氮合酶(β)3-肾上腺素能受体(AR)及其下游信号转导通路是一种新型的心功能调节剂，甚至是心血管疾病的潜在治疗靶点。然而，β-3-AR对心肌梗死(MI)损伤是否具有心脏保护作用尚不清楚。因此，本研究旨在探讨β-3-AR在心肌损伤中的作用及其机制。结扎左前降支(LAD)建立MI模型。心肌梗死后1d分别给予β3-AR激动剂BRL37344(BRL)或β3-AR抑制剂SR59230A(SR)，剂量为0.1 mg/kg/h。分别用Masson‘s三色染色、超声心动图和原位末端标记法检测瘢痕面积、心功能和心肌细胞凋亡率。Western印迹分析目的蛋白的表达。β3-AR的激活和BRL的应用显著减轻了心肌梗死后的纤维化和减少了瘢痕面积。此外，BRL还能保护心功能，减少心肌梗死所致的心肌细胞凋亡。此外，BRL治疗还改变了内皮型一氧化氮合酶(ENOS)的磷酸化状态，增加了神经元型一氧化氮合酶(NNOS)的表达。这些结果提示，刺激β-3-AR对心功能的恢复有重要作用。此外，eNOS和nNOS的激活可能与β-3-AR的心脏保护作用有关。
β3-adrenergic receptor (AR) and the downstream signaling, nitric oxide synthase (NOS) isoforms, have been emerged as novel modulators of heart function and even potential therapeutic targets for cardiovascular diseases. However, it is not known whether β3-AR plays cardioprotective effects against myocardial infarction (MI) injury. Therefore, the present study was designed to determine the effects of β3-AR on MI injury and to elucidate the underlying mechanism. MI model was constructed by left anterior descending (LAD) artery ligation. Animals were administrated with β3-AR agonist BRL37344 (BRL) or β3-AR inhibitor SR59230A (SR) respectively at 0.1 mg/kg/hour one day after MI operation. The scar area, cardiac function and the apoptosis of myocardial were assessed by Masson's trichrome stain, echocardiography and TUNEL assay respectively. Western blot analysis was performed to elucidate the expressions of target proteins. β3-AR activation with BRL administration significantly attenuated fibrosis and decreased scar area after MI. Moreover, BRL also preserved heart function, and reduced the apoptosis of cardiomyocyte induced by MI. Furthermore, BRL treatment altered the phosphorylation status of endothelial NOS (eNOS) and increased the expression of neuronal NOS (nNOS). These results suggested that β3-AR stimulation has a substantial effect on recovery of heart function. In addition, the activations of both eNOS and nNOS may be associated with the cardiac protective effects of β3-AR.
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影响因子：
20.1
作者：
Calvert JW;Condit ME;Aragón JP;Nicholson CK;Moody BF;Hood RL;Sindler AL;Gundewar S;Seals DR;Barouch LA;Lefer DJ
通讯作者：
Lefer DJ
影响因子：
37.8
作者：
Bendall, JK;Damy, T;Heymes, C
通讯作者：
Heymes, C
影响因子：
15.9
作者：
Gauthier, C;Tavernier, G;LeMarec, H
通讯作者：
LeMarec, H
影响因子：
3.6
作者：
Hoffmann, C;Leitz, MR;Klotz, KN
通讯作者：
Klotz, KN
影响因子：
37.8
作者：
Reiken, S;Wehrens, XHT;Marks, AR
通讯作者：
Marks, AR