Cyclin A2 mediates cardiomyocyte mitosis in the postmitotic myocardium

被引:160
作者
Chaudhry, HW
Dashoush, NH
Tang, HY
Zhang, L
Wang, XY
Wu, EX
Wolgemuth, DJ
机构
[1] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA
[2] Columbia Univ Coll Phys & Surg, Dept Radiol, New York, NY 10032 USA
[3] Columbia Univ Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA
[4] Columbia Univ Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY 10032 USA
[5] Columbia Univ Coll Phys & Surg, Ctr Reprod Sci, New York, NY 10032 USA
[6] Columbia Univ Coll Phys & Surg, Inst Human Nutr, New York, NY 10032 USA
关键词
D O I
10.1074/jbc.M404975200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cell cycle withdrawal limits proliferation of adult mammalian cardiomyocytes. Therefore, the concept of stimulating myocyte mitotic divisions has dramatic implications for cardiomyocyte regeneration and hence, cardiovascular disease. Previous reports describing manipulation of cell cycle proteins have not shown induction of cardiomyocyte mitosis after birth. We now report that cyclin A2, normally silenced in the postnatal heart, induces cardiac enlargement because of cardiomyocyte hyperplasia when constitutively expressed from embryonic day 8 into adulthood. Cardiomyocyte hyperplasia during adulthood was coupled with an increase in cardiomyoctye mitosis, noted in transgenic hearts at all time points examined, particularly during postnatal development. Several stages of mitosis were observed within cardiomyocytes and correlated with the nuclear localization of cyclin A2. Magnetic resonance analysis confirmed cardiac enlargement. These results reveal a previously unrecognized critical role for cyclin A2 in mediating cardiomyocyte mitosis, a role that may significantly impact upon clinical treatment of damaged myocardium.
引用
收藏
页码:35858 / 35866
页数:9
相关论文
共 43 条
  • [31] INHIBITORS OF MAMMALIAN G(1) CYCLIN-DEPENDENT KINASES
    SHERR, CJ
    ROBERTS, JM
    [J]. GENES & DEVELOPMENT, 1995, 9 (10) : 1149 - 1163
  • [32] SIMPSON PC, 1989, ANNU REV PHYSIOL, V51, P189, DOI 10.1146/annurev.physiol.51.1.189
  • [33] Cardiac MRI of the normal and hypertrophied mouse heart
    Slawson, SE
    Roman, BB
    Williams, DS
    Koretsky, AP
    [J]. MAGNETIC RESONANCE IN MEDICINE, 1998, 39 (06) : 980 - 987
  • [34] Soonpaa MH, 1996, AM J PHYSIOL-HEART C, V271, pH2183
  • [35] Cyclin D1 overexpression promotes cardiomyocyte DNA synthesis and multinucleation in transgenic mice
    Soonpaa, MH
    Koh, GY
    Pajak, L
    Jing, SL
    Wang, H
    Franklin, MT
    Kim, KK
    Field, LJ
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (11) : 2644 - 2654
  • [36] Survey of studies examining mammalian cardiomyocyte DNA synthesis
    Soonpaa, MH
    Field, LJ
    [J]. CIRCULATION RESEARCH, 1998, 83 (01) : 15 - 26
  • [37] ACIDIC AND BASIC FIBROBLAST GROWTH-FACTORS IN ADULT-RAT HEART MYOCYTES - LOCALIZATION, REGULATION IN CULTURE, AND EFFECTS ON DNA-SYNTHESIS
    SPEIR, E
    TANNER, V
    GONZALEZ, AM
    FARRIS, J
    BAIRD, A
    CASSCELLS, W
    [J]. CIRCULATION RESEARCH, 1992, 71 (02) : 251 - 259
  • [38] SUBRAMANIAM A, 1991, J BIOL CHEM, V266, P24613
  • [39] Tang HY, 2000, ANN NY ACAD SCI, V904, P32
  • [40] Wei L, 2002, DEVELOPMENT, V129, P1705