Protein kinase Cα as a heart failure therapeutic target.
Protein kinase Cα as a heart failure therapeutic target.
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DOI：
10.1016/j.yjmcc.2010.10.004
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发表时间：
2011-10
影响因子：
5
通讯作者：
Molkentin JD
中科院分区：
文献类型：
--
作者：
Liu Q;Molkentin JD
仅在美国，每年就有约500万人遭受心力衰竭的折磨，并导致约30万人死亡。心力衰竭被定义为心脏缺乏对全身需求泵出足够血液的能力，这会导致疲劳、呼吸困难和/或浮肿。寻找新的治疗靶点是当前该领域研究的主要焦点。我们和其他人已经确定了蛋白激酶C(PKC)家族成员在心力衰竭发病机制编程方面的关键作用。更具体地说，过去6-7年出现的机制数据直接表明PKCα，一个传统的PKC家族成员，是心力衰竭倾向的节点调节因子。事实上，小鼠PKCα基因的缺失，或者用药物或显性负性突变体和/或抑制性多肽抑制其在啮齿动物中的表达，都显示出显著的保护作用，从而对抗心力衰竭的发展。这篇综述将权衡所有涉及PKCα作为治疗心力衰竭的新靶点的证据。
Heart failure afflicts ~5 million people and causes ~300,000 deaths a year in the United States alone. Heart failure is defined as a deficiency in the ability of the heart to pump sufficient blood in response to systemic demands, which results in fatigue, dyspnea, and/or edema. Identifying new therapeutic targets is a major focus of current research in the field. We and others have identified critical roles for protein kinase C (PKC) family members in programming aspects of heart failure pathogenesis. More specifically, mechanistic data have emerged over the past 6–7 years that directly implicate PKCα, a conventional PKC family member, as a nodal regulator of heart failure propensity. Indeed, deletion of the PKCα gene in mice, or its inhibition in rodents with drugs or a dominant negative mutant and/or inhibitory peptide, have shown dramatic protective effects that antagonize the development of heart failure. This review will weigh all the evidence implicating PKCα as a novel therapeutic target to consider for the treatment of heart failure.
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影响因子：
20.1
作者：
Hidalgo C;Hudson B;Bogomolovas J;Zhu Y;Anderson B;Greaser M;Labeit S;Granzier H
通讯作者：
Granzier H
影响因子：
4.3
作者：
Koch, WJ
通讯作者：
Koch, WJ
影响因子：
4.3
作者：
Bayer, AL;Heidkamp, MC;Samarel, AM
通讯作者：
Samarel, AM
影响因子：
82.9
作者：
Braz, JC;Gregory, K;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
20.1
作者：
GU, X;BISHOP, SP
通讯作者：
BISHOP, SP