A new tale of p21 activated protein kinase in the heart:pathophysiology to drug discovery / 中国药理学与毒理学杂志

ABSTRACT

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.