Specific PI3K isoform modulation in heart failure: lessons from transgenic mice.
Specific PI3K isoform modulation in heart failure: lessons from transgenic mice.
复制标题
DOI：
10.1007/s11897-011-0059-3
复制
发表时间：
2011-09-01
影响因子：
--
通讯作者：
Hirsch, Emilio
中科院分区：
文献类型：
--
作者：
Ghigo, Alessandra;Morello, Fulvio;Hirsch, Emilio
心脏病理生理在很大程度上依赖于受体介导的信号转导，这种生物过程的药物控制已被证明在预防和治疗多种心脏病方面取得了成功。最近在心脏中受体介导的信号转导事件的研究进展强调了脂质激酶家族的作用，即磷酸肌肽3激酶（PI3Ks）。这些酶参与下游不同受体产生脂质第二信使分子(即磷脂酰肌醇（3,4,5)-三磷酸[PIP(3)]），介导大量对心脏至关重要的生物反应，包括心肌细胞生长、存活、收缩以及心血管炎症。本文通过对小鼠不同PI3K基因突变体的研究，以及在心衰等危重心脏疾病的临床前模型中验证PI3K的药理抑制作用，综述了近年来对PI3K在心脏病理生理中的功能的研究进展。
Cardiac pathophysiology heavily relies on receptor-mediated signal transduction, and pharmacologic control of such biological processes has proven successful in preventing and treating multiple heart diseases. Recent progress in the study of receptor-mediated signal transduction events in the heart highlighted the role of a family of lipid kinases known as phosphoinositide 3-kinases (PI3Ks). These enzymes are involved downstream different receptors in the production of a lipid second messenger molecule (namely phosphatidylinositol (3,4,5)-trisphosphate [PIP(3)]), which mediates a large number of biological responses critical for the heart, including cardiomyocyte growth, survival, and contractility as well as cardiovascular inflammation. This review focuses on the recent advances in the understanding of PI3K function in cardiac pathophysiology obtained by studying mouse mutants for different PI3K genes and by validating the effects of PI3K pharmacologic inhibition in preclinical models of critical cardiac diseases like heart failure.