Genetic and phenotypic targeting of β-adrenergic signaling in heart failure
Genetic and phenotypic targeting of β-adrenergic signaling in heart failure
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DOI：
10.1023/b:mcbi.0000041843.64809.48
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发表时间：
2004-08-01
影响因子：
4.3
通讯作者：
Koch, WJ
中科院分区：
文献类型：
--
作者：
Koch, WJ
心力衰竭是全世界住院的主要原因。尽管疾病管理取得了进展，但过去几十年来心力衰竭的预后并未取得重大改善。心力衰竭本身代表了几种疾病的最终共同终点，包括高血压和冠状动脉疾病。在分子水平上，某些生化特征对于衰竭的心肌来说仍然是常见的。其中包括β-肾上腺素能受体（β-AR）信号级联的改变。转基因和基因治疗技术的最新进展提出了通过对 β-AR 信号传导进行基因操作来治疗心力衰竭的新治疗策略，包括靶向抑制 β-AR 激酶（βARK1 或 GRK2）。在这篇综述中，我们将讨论伴随心力衰竭的β-AR信号传导变化以及相应的治疗策略。然后，我们将回顾来自转基因小鼠工作的证据，这些证据支持在衰竭的心脏中使用 β-AR 操作，以及最近针对逆转或预防心力衰竭的基因治疗的体内应用。
Heart failure is a leading cause of hospitalization worldwide. No major significant improvements in prognosis have been achieved for heart failure over the last several decades despite advances in disease management. Heart failure itself represents a final common endpoint for several disease entities, including hypertension and coronary artery disease. On a molecular level, certain biochemical features remain common to failing myocardium. Among these are alterations in the beta-adrenergic receptor (beta-AR) signaling cascade. Recent advances in transgenic and gene therapy techniques have presented novel therapeutic strategies for management of heart failure via genetic manipulation of beta-AR signaling including the targeted inhibition of the beta-AR kinase (betaARK1 or GRK2). In this review, we will discuss the beta-AR signaling changes that accompany heart failure as well as corresponding therapeutic strategies. We will then review the evidence from transgenic mouse work supporting the use of beta-AR manipulation in the failing heart and more recent in vivo applications of gene therapy directed at reversing or preventing heart failure.