p38α Mitogen-Activated Protein Kinase Plays a Critical Role in Cardiomyocyte Survival but Not in Cardiac Hypertrophic Growth in Response to Pressure Overload

• DOI: 10.1128/mcb.24.24.10611-10620.2004
• Publication Date: 2004-11-30T21:13:33Z
• Authors: Kazuhiko Nishida; Osamu Yamaguchi; Shinichi Hirotani; Shungo Hikoso; Yoshiharu Higuchi; Tetsuya Watanabe; Toshihiro Takeda; Soh Osuka; Takashi Morita; Gen Kondoh; Yoshihiro Uno; Kazunori Kashiwase; Masayuki Taniike; Atsuko Nakai; Yasushi Matsumura; Jun-ichi Miyazaki; Tatsuhiko Sudo; Kenichi Hongo; Yoichiro Kusakari; Satoshi Kurihara; Kenneth R. Chien; Junji Takeda; Masatsugu Hori; Kinya Otsu
• Keywords: Pressure overload; Cardiac Fibrosis

The molecular mechanism for the transition from cardiac hypertrophy, an adaptive response to biomechanical stress, heart failure is poorly understood. mitogen-activated protein kinase p38alpha a key component of stress pathways in various types cells. In this study, we attempted explore vivo physiological functions hearts. First, generated mice with floxed alleles and crossbred them expressing Cre recombinase under control alpha-myosin heavy-chain promoter obtain cardiac-specific knockout mice. These were born normally, developed adulthood, fertile, exhibited normal life span, displayed global structure function. pressure overload left ventricle, they significant levels as seen controls, but also dysfunction dilatation. This abnormal was accompanied by massive fibrosis appearance apoptotic cardiomyocytes. results demonstrate that plays critical role cardiomyocyte survival pathway overload, while hypertrophic growth unaffected despite its dramatic down-regulation.