The novel adipocytokine visfatin exerts direct cardioprotective effects.
The novel adipocytokine visfatin exerts direct cardioprotective effects.
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DOI：
10.1111/j.1582-4934.2008.00332.x
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发表时间：
2008-08
影响因子：
5.3
通讯作者：
Hausenloy DJ
中科院分区：
文献类型：
--
作者：
Lim SY;Davidson SM;Paramanathan AJ;Smith CC;Yellon DM;Hausenloy DJ
Visfatin 是一种脂肪细胞因子，能够模拟胰岛素的降血糖作用，并激活促生存激酶磷脂酰肌醇-3-OH 激酶 (PI3K)-蛋白激酶 B (Akt) 和丝裂原激活蛋白激酶激酶 1 和 2 (MEK1/2)-细胞外信号调节激酶 1 和 2（Erk 1/2）。实验研究表明，这些激酶的激活通过抑制线粒体通透性转换孔 (mPTP) 提供心脏保护作用。内脂素是否能够通过这些机制发挥直接的心脏保护作用尚不清楚，也是当前研究的主题。对麻醉的 C57BL/6 雄性小鼠进行原位 30 分钟。局部心肌缺血120分钟。再灌注。心肌再灌注时静脉推注内脂素 (5 × 10−6μmol) 可将对照心脏中的心肌梗死面积从 46.1 ± 4.1% 减少至 27.3 ± 4.0%（n≥ 6/组，P < 0.05），这一作用被 PI3K 抑制剂、渥曼青霉素和 MEK1/2 阻断 抑制剂 U0126（分别为 48.8 ± 5.5% 和 45.9 ± 8.4%，而内脂素为 27.3 ± 4.0%；n≥ 6/组，P < 0.05）。小鼠心室心肌细胞经受 30 分钟。缺氧后30分钟。复氧时，复氧时给予内脂素 (100 ng/ml)，可将细胞死亡率从对照的 65.2 ± 4.6% 降低至 49.2 ± 3.7%（n > 200 个细胞/组，P < 0.05），该效果被渥曼青霉素和 U0126 消除（68.1 ± 5.2% 和 59.7 ±分别为 6.2%；n > 200 细胞/组，P > 0.05）。最后，用内脂素 (100 ng/ml) 处理小鼠心室心肌细胞，将氧化应激诱导的 mPTP 开放时间从 81.2 ± 4 秒延迟。控制在120±7秒。 (n > 20 个细胞/组，P < 0.05) 以 PI3K 和 MEK1/2 依赖性方式。我们报道，在原位小鼠心脏和分离的小鼠心肌细胞的心肌再灌注时施用脂肪细胞因子内脂素能够减少心肌损伤。该机制似乎涉及 PI3K 和 MEK1/2 途径以及 mPTP。
Visfatin is an adipocytokine capable of mimicking the glucose-lowering effects of insulin and activating the pro-survival kinases phosphatidylinositol-3-OH kinase (PI3K)-protein kinase B (Akt) and mitogen-activated protein kinase kinase 1 and 2 (MEK1/2)-extracellular signal-regulated kinase 1 and 2 (Erk 1/2). Experimental studies have demonstrated that the activation of these kinases confers cardioprotection through the inhibition of the mitochondrial permeability transition pore (mPTP). Whether visfatin is capable of exerting direct cardioprotective effects through these mechanisms is unknown and is the subject of the current study. Anaesthetized C57BL/6 male mice were subjected to in situ 30 min. of regional myocardial ischaemia and 120 min. of reperfusion. The administration of an intravenous bolus of visfatin (5 × 10−6μmol) at the time of myocardial reperfusion reduced the myocardial infarct size from 46.1 ± 4.1% in control hearts to 27.3 ± 4.0% (n≥ 6/group, P < 0.05), an effect that was blocked by the PI3K inhibitor, wortmannin, and the MEK1/2 inhibitor, U0126 (48.8 ± 5.5% and 45.9 ± 8.4%, respectively, versus 27.3 ± 4.0% with visfatin; n≥ 6/group, P < 0.05). In murine ventricular cardiomyocytes subjected to 30 min. of hypoxia followed by 30 min. of reoxygenation, visfatin (100 ng/ml), administered at the time of reoxygenation, reduced the cell death from 65.2 ± 4.6% in control to 49.2 ± 3.7%(n > 200 cells/group, P < 0.05), an effect that was abrogated by wortmannin and U0126 (68.1 ± 5.2% and 59.7 ± 6.2%, respectively; n > 200 cells/group, P > 0.05). Finally, the treatment of murine ventricular cardiomyocytes with visfatin (100 ng/ml) delayed the opening of the mPTP induced by oxidative stress from 81.2 ± 4 sec. in control to 120 ± 7 sec. (n > 20 cells/group, P < 0.05) in a PI3K- and MEK1/2-dependent manner. We report that the adipocytokine, visfatin, is capable of reducing myocardial injury when administered at the time of myocardial reperfusion in both the in situ murine heart and the isolated murine cardiomyocytes. The mechanism appears to involve the PI3K and MEK1/2 pathways and the mPTP.
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影响因子：
16.2
作者：
Isomaa, B;Almgren, P;Groop, L
通讯作者：
Groop, L
影响因子：
10.8
作者：
Lim, Shiang Y.;Davidson, Sean M.;Hausenloy, Derek J.;Yellon, Derek M.
通讯作者：
Yellon, Derek M.
影响因子：
5.8
作者：
Chen, MP;Chung, FM;Lee, YJ
通讯作者：
Lee, YJ
DOI：
10.1152/ajplung.00266.2006
发表时间：
2006-12-01
影响因子：
4.9
作者：
Garcia, Joe G. N.;Vinasco, Liliana Moreno
通讯作者：
Vinasco, Liliana Moreno
影响因子：
3.5
作者：
Ognjanovic, S;Bao, S;Bryant-Greenwood, GD
通讯作者：
Bryant-Greenwood, GD