CAJ | 학술논문

在全世界范围内，心血管疾病的发病率和死亡率一直都是排在首位的。从心脏信号转导这一新兴领域寻找新疗法的可能性促使人们在过去几十年中对心肌重塑开展了广泛深入研究。本综述将对一种丝氨酸/苏氨酸蛋白激酶p21活化激酶1（Pak1）在心脏方面，特别是其心脏保护作用的研究进展作一回顾。我们提出一种 Pak1信号转导模型，揭示其特异性影响心脏细胞进程的机制；进而从抗心肌肥厚，抗缺血性损伤以及在生理条件、β-肾上腺素能和肥厚性应激条件下维持心室钙稳态和电生理稳定性的角度探讨它的心脏保护作用。此外，还将通过天然存在的鞘氨醇及其类似物 FTY720，以及旨在减少 Pak1自抑制而设计的生物活性肽的研究实例来讨论 Pak1激活作为心血管疾病新型疗法以及开展药物研发的可能性。
재전세계범위내，심혈관질병적발병솔화사망솔일직도시배재수위적。종심장신호전도저일신흥영역심조신요법적가능성촉사인문재과거궤십년중대심기중소개전료엄범심입연구。본종술장대일충사안산/소안산단백격매p21활화격매1（Pak1）재심장방면，특별시기심장보호작용적연구진전작일회고。아문제출일충 Pak1신호전도모형，게시기특이성영향심장세포진정적궤제；진이종항심기비후，항결혈성손상이급재생리조건、β-신상선소능화비후성응격조건하유지심실개은태화전생리은정성적각도탐토타적심장보호작용。차외，환장통과천연존재적초안순급기유사물 FTY720，이급지재감소 Pak1자억제이설계적생물활성태적연구실례래토론 Pak1격활작위심혈관질병신형요법이급개전약물연발적가능성。
CardiovascuIar disease is the number one cause for morbidity and mortaIity worIdwide. Possi-biIities for new therapies in the emerging fieId of cardiac signaIIing prompted extensive research on myocardiaI re-modeIIing over the past decades. In this review,we as-sembIe an overview of the recent findings on the muIti-functionaI enzyme,p21-activated kinase 1( Pak1),a member of a serine/ threonine protein kinase famiIy in the heart,particuIarIy its cardiac protective effects. We pres-ent a modeI for Pak1 signaIing that provides a mecha-nism for specificaIIy affecting cardiac ceIIuIar processes. We discuss its cardiac protective effects such as anti-hy-pertrophy,anti-ischaemic injury and roIe in maintaining ventricuIar Ca2+ homeostasis and eIectrophysioIogicaI stabiIity under physioIogicaI, β-adrenergic and hyper-trophic stress conditions.We aIso discuss the potentiaIs of Pak1 activation by naturaIIy occurring sphingosine and its anaIogues FTY720,and bioactive peptides designed to diminish Pak1 auto-inhibition as noveI thera-peutics for major cardiovascuIar diseases.