生物谷报道：心脏疾病的机理研究一直是人们研究的焦点。最新研究发现磷脂酶4D3是其中的关键性因子之一。它的缺陷，能直接促进心力衰竭和心律失常。其机制是因为它可以促进cAMP降解，从而使RyR2通道活性下降。因此临床在应用磷脂酶抑制剂类药物时要考虑它对心脏的影响。在此前Nature一篇报道也从另一个方面揭示了其重要作用：Nature：与mAKAP相关的心脏疾病信号调控环路被揭示
Contraction of the heart increases in response to sympathetic nervous system activation during the “fight or flight” stress response. This induction is mediated by cAMP-dependent protein kinase (PKA), which activates the ryanodine receptor (RyR2) channel to release more calcium and increase heart muscle contraction. Here, Lehnart et al. show that the phosphodiesterase PDE4D3, which degrades cAMP, is critical to prevent excessive activation of the RyR2 channel. PDE4D3 deficiency in mice causes cardiomyopathy and cardiac arrhythmias due to PKA-hyperphosphorylated, leaky RyR2 channels. These data raise concerns that patients treated with PDE4 inhibitors may be prone to cardiac dysfunction and arrhythmias.
原文来源：
S.E. Lehnart, X.H.T. Wehrens, S. Reiken, S. Warrier, A.E. Belevych, R.D. Harvey, W. Richter, S.-L.C. Jin, M. Conti, and A.R. Marks Phosphodiesterase 4D Deficiency in the Ryanodine-Receptor Complex Promotes Heart Failure and Arrhythmias Cell, Vol 123, 25-35, 7 October 2005
