Akt promotes increased cardiomyocyte cycling and expansion of the cardiac progenitor cell population

被引:95
作者
Gude, Natalie
Muraski, John
Rubio, Marta
Kajstura, Jan
Schaefer, Erik
Anversa, Piero
Sussman, Mark A.
机构
[1] San Diego State Univ, Heart Inst, San Diego, CA 92182 USA
[2] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA
[3] Cardiovasc Res Inst, New York Med Coll, Valhalla, NY USA
[4] Biosource Int, Hopkinton, MA USA
关键词
PKB/Akt; cardiac stem cell; proliferation; cytokines; postnatal growth;
D O I
10.1161/01.RES.0000236754.21499.1c
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Activation of Akt is associated with enhanced cell cycling and cellular proliferation in nonmyocytes, but this effect of nuclear Akt accumulation has not been explored in the context of the myocardium. Cardiac-specific expression of nuclear-targeted Akt (Akt/nuc) in transgenics prolongs postnatal cell cycling as evidenced by increased numbers of Ki67(+) cardiomyocytes at 2 to 3 weeks after birth. Similarly, nuclear-targeting of Akt promotes expansion of the presumptive cardiac progenitor cell population as assessed by immunolabeling for c-kit in combination with myocyte-specific markers Nkx 2.5 or MEF 2C. Increases in pro-proliferative cytokines, including tumor-necrosis superfamily 8, interleukin-17e, and hepatocyte growth factor, were found in nuclear-targeted Akt myocardial samples. Concurrent signaling mediated by paracrine factors downstream of Akt/nuc expression may be responsible for phenotypic effects of nuclear-targeted Akt in the myocardium, including enhanced cell proliferation and expansion of the stem cell population.
引用
收藏
页码:381 / 388
页数:8
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