Matsui Takashi, Nagoshi Tomohisa, Rosenzweig Anthony
Program in Cardiovascular Gene Therapy, CVRC and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Room 2600, Boston, MA 02129, USA.
Cell Cycle. 2003 May-Jun;2(3):220-3.
In many systems, activation of the "protein and lipid kinase" phosphoinositide 3-kinase (PI 3-kinase) and its downstream serine-threonine kinase effector, Akt (or Protein Kinase B), provide a potent stimulus for cell proliferation, growth, and survival. In the heart, constrained by the limited proliferative capacity of cardiomyocytes, this pathway plays a key role in regulating cardiomyocyte growth and survival, with little effect on proliferation. Simultaneously, PI 3-kinase and Akt are important modulators of metabolic substrate utilization and cardiomyocyte function. Thus, the convergent signaling pathways controlling so many clinically important phenotypes of the cardiomyocyte suggest it holds promise as a therapeutic target in a variety of cardiac diseases. However, the similar role of PI 3-kinase/Akt signaling in neoplasia suggests the difficulty of activating this pathway in the heart without invoking adverse consequences elsewhere. Here we review evidence regarding the role of PI 3-kinase/Akt in controlling cardiomyocyte growth and survival, and discuss the implications for therapeutic strategies.
在许多系统中，“蛋白质和脂质激酶”磷酸肌醇3激酶（PI 3激酶）及其下游的丝氨酸 - 苏氨酸激酶效应器Akt（或蛋白激酶B）的激活，为细胞增殖、生长和存活提供了强大的刺激。在心脏中，由于心肌细胞增殖能力有限，该信号通路在调节心肌细胞生长和存活中起关键作用，对增殖影响较小。同时，PI 3激酶和Akt是代谢底物利用和心肌细胞功能的重要调节因子。因此，控制心肌细胞如此多临床重要表型的汇聚信号通路表明，它有望成为多种心脏疾病的治疗靶点。然而，PI 3激酶/Akt信号在肿瘤形成中的类似作用表明，在心脏中激活该信号通路而不引发其他不良后果存在困难。在此，我们综述了关于PI 3激酶/Akt在控制心肌细胞生长和存活中作用的证据，并讨论其对治疗策略的影响。
