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(Circulation Research. 2008;103:89.)
© 2008 American Heart Association, Inc.

Integrative Physiology

Myocardial Induction of Nucleostemin in Response to Postnatal Growth and Pathological Challenge

Sailay Siddiqi, Natalie Gude, Toru Hosoda, John Muraski, Marta Rubio, Gregory Emmanuel, Jenna Fransioli, Serena Vitale, Carola Parolin, Domenico D'Amario, Erik Schaefer, Jan Kajstura, Annarosa Leri, Piero Anversa, Mark A. Sussman

From the San Diego State University Heart Institute and Department of Biology (S.S., N.G., J.M., M.R., G.E., J.F., M.A.S.), San Diego State University, Calif; Departments of Anesthesia and Medicine and Division of Cardiology (T.H., S.V., C.P., D.D'A., J.K., A.L., P.A.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; and Biosource International (E.S.), Hopkinton, Mass.

Correspondence to Mark Sussman SDSU Heart Institute and Department of Biology, San Diego State University, 5500 Campanile Dr, San Diego, CA 92182. E-mail sussman{at}heart.sdsu.edu

Stem cell–specific proteins and regulatory pathways that determine self-renewal and differentiation have become of fundamental importance in understanding regenerative and reparative processes in the myocardium. One such regulatory protein, named nucleostemin, has been studied in the context of stem cells and several cancer cell lines, where expression is associated with proliferation and maintenance of a primitive cellular phenotype. We find nucleostemin is present in young myocardium and is also induced following cardiomyopathic injury. Nucleostemin expression in cardiomyocytes is induced by fibroblast growth factor-2 and accumulates in response to Pim-1 kinase activity. Cardiac stem cells also express nucleostemin that is diminished in response to commitment to a differentiated phenotype. Overexpression of nucleostemin in cultured cardiac stem cells increases proliferation while preserving telomere length, providing a mechanistic basis for potential actions of nucleostemin in promotion of cell survival and proliferation as seen in other cell types.

Key Words: nucleostemin • cardioprotection • cardiomyocytes • stem cells • Pim-1 • telomerase

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