In search of new therapeutic targets and strategies for heart failure: recent advances in basic science.
In search of new therapeutic targets and strategies for heart failure: recent advances in basic science.
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DOI：
10.1016/s0140-6736(11)60894-5
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发表时间：
2011-08-20
期刊：
影响因子：
168.9
通讯作者：
Mann, Douglas L.
中科院分区：
文献类型：
--
作者：
Shah, Ajay M.;Mann, Douglas L.
尽管最近的治疗取得了进展，但慢性心力衰竭继续给医疗带来巨大的负担。最终导致慢性心力衰竭的关键病理生理过程是心脏重构，以应对慢性疾病应激。在这里，我们回顾了在复杂的重塑过程中发挥作用的分子和细胞机制的最新进展，重点介绍了可能适合作为治疗操作靶点的关键分子和途径。这些途径包括那些调节心肌细胞肥大、钙稳态、能量和细胞存活的途径，以及发生在心肌细胞外的过程--例如，在心肌血管和细胞外基质中。我们还讨论了目前理解中的主要差距，对迄今已使用的靶向发现的传统方法进行了批判性审查，并考虑了可能加速临床相关发现的新的研究途径。
Chronic heart failure continues to impose a substantial health-care burden, despite recent treatment advances. The key pathophysiological process that ultimately leads to chronic heart failure is cardiac remodelling in response to chronic disease stresses. Here, we review recent advances in our understanding of molecular and cellular mechanisms that play a part in the complex remodelling process, with a focus on key molecules and pathways that might be suitable targets for therapeutic manipulation. Such pathways include those that regulate cardiac myocyte hypertrophy, calcium homoeostasis, energetics, and cell survival, and processes that take place outside the cardiac myocyte—eg, in the myocardial vasculature and extracellular matrix. We also discuss major gaps in our current understanding, take a critical look at conventional approaches to target discovery that have been used to date, and consider new investigational avenues that might accelerate clinically relevant discovery.