The PGC-1 cascade as a therapeutic target for heart failure.

The PGC-1 cascade as a therapeutic target for heart failure.
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DOI:
10.1016/j.yjmcc.2010.09.021
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发表时间:
2011-10
影响因子:
5
通讯作者:
Kelly DP
Kelly DP
中科院分区:
医学2区
文献类型:
--
作者:
Schilling J;Kelly DP

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过氧化物酶体增殖物激活受体γ共激活因子-1(PGC-1)家族与雌激素相关受体(ERRs)一起在调节心肌燃料代谢和心功能相关基因中发挥关键作用。越来越多的证据表明,这种转录调控回路的失调与代谢和功能紊乱有关,这些紊乱预示着常见疾病如高血压和糖尿病引起的心力衰竭。因此,PGC-1/ERR轴是旨在逆转导致心力衰竭的能量代谢紊乱的新疗法的合理候选治疗靶标。本文综述了PGC-1和ERR级联的生物学作用,并总结了这种转录调控回路失调导致心力衰竭的证据。潜在的策略来调节这一目标途径进行审查。
The PPARγ coactivator-1 (PGC-1) family of transcriptional coactivators, together with estrogen related receptors (ERRs), play a key role in regulating genes involved in myocardial fuel metabolism and cardiac function. Increasing evidence implicates dysregulation of this transcriptional regulatory circuit in the metabolic and functional disturbances that presage heart failure due to common diseases such as hypertension and diabetes. Accordingly, the PGC-1/ERR axis is a plausible candidate therapeutic target for novel therapeutics aimed at reversing the energy metabolic disturbances that contribute to heart failure. This review describes the biologic actions of the PGC-1 and ERR cascade and summarizes the evidence that dysregulation of this transcriptional regulatory circuit contributes to heart failure. Potential strategies to modulate this target pathway are reviewed.
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