Published online before print July 13, 2006, doi: 10.1161/01.RES.0000236754.21499.1c
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Submitted on January 31, 2006
Revised on June 20, 2006
Accepted on June 28, 2006
Akt Promotes Increased Cardiomyocyte Cycling and Expansion of the Cardiac Progenitor Cell Population
Natalie Gude ;
From the San Diego State University Heart Institute, Department of Biology (N.G., J.M., M.R., M.S.), San Diego State University; the New York Medical College, Cardiovascular Research Institute (J.K., P.A.), Valhalla, NY; and Biosource International (E.S.), Hopkinton, Mass.
* To whom correspondence should be addressed. E-mail: sussman{at}heart.sdsu.edu.
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 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.
Key words: PKB/Akt • cardiac stem cell • proliferation • cytokines • postnatal growth
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