Protein Kinase C Inhibition With Ruboxistaurin Increases Contractility and Reduces Heart Size in a Swine Model of Heart Failure With Reduced Ejection Fraction.
Protein Kinase C Inhibition With Ruboxistaurin Increases Contractility and Reduces Heart Size in a Swine Model of Heart Failure With Reduced Ejection Fraction.
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使用 Ruboxistaurin 抑制蛋白激酶 C 可增加心力衰竭猪模型的收缩性并减小心脏大小，并减少射血分数。
DOI：
10.1016/j.jacbts.2017.06.007
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Houser,StevenR
中科院分区：
文献类型：
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作者：
Sharp3rd,ThomasE;Kubo,Hajime;Berretta,RemusM;Starosta,Timothy;Wallner,Markus;Schena,GianaJ;Hobby,AlexanderR;Yu,Daohai;Trappanese,DanielleM;George,JonC;Molkentin,JefferyD;Houser,StevenR
急性失代偿性心力衰竭患者通常需要正性肌力支持来稳定血流动力学；虽然有效，但它有导致致命性心律失常和/或加剧收缩和能量不足的历史。能够独立于 β-肾上腺素能和蛋白激酶 A 调节信号传导而改善收缩性的新型疗法应该具有治疗益处。这项研究表明，在心肌梗塞后 3 个月使用 ruboxistaurin 进行急性蛋白激酶 C-α/β 抑制，可显着增加收缩力并减少舒张末期/收缩末期容积，从而记录了有益的重构。这些数据表明，ruboxistaurin 代表了心力衰竭患者的一种潜在的新型治疗方法，作为一种温和的正性肌力药或治疗剂，可导致有益的心室重塑。
Inotropic support is often required to stabilize the hemodynamics of patients with acute decompensated heart failure; while efficacious, it has a history of leading to lethal arrhythmias and/or exacerbating contractile and energetic insufficiencies. Novel therapeutics that can improve contractility independent of beta-adrenergic and protein kinase A-regulated signaling, should be therapeutically beneficial. This study demonstrates that acute protein kinase C-α/β inhibition, with ruboxistaurin at 3 months’ post-myocardial infarction, significantly increases contractility and reduces the end-diastolic/end-systolic volumes, documenting beneficial remodeling. These data suggest that ruboxistaurin represents a potential novel therapeutic for heart failure patients, as a moderate inotrope or therapeutic, which leads to beneficial ventricular remodeling.