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Cardiac myocyte p38α kinase regulates angiogenesis via myocyte-endothelial cell cross-talk during stress-induced remodeling in the heart.
Rose, Beth A; Yokota, Tomohiro; Chintalgattu, Vishnu; Ren, Shuxun; Iruela-Arispe, Luisa; Khakoo, Aarif Y; Minamisawa, Susumu; Wang, Yibin.
Afiliación
  • Rose BA; Departments of Anesthesiology, Physiology, and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, California 90095.
  • Yokota T; Departments of Anesthesiology, Physiology, and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, California 90095; Department of Life Science and Medical Bioscience, Waseda University, 3-4-1 Okubo, Shinjuku-ku, 169-8555, Japan.
  • Chintalgattu V; Amgen, Inc., Metabolic Disorders, South San Francisco, California 94080.
  • Ren S; Departments of Anesthesiology, Physiology, and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, California 90095.
  • Iruela-Arispe L; Department of Molecular, Cellular, and Developmental Biology, Molecular Biology Institute, School of Life Sciences, University of California, Los Angeles, California 90095.
  • Khakoo AY; Amgen, Inc., Metabolic Disorders, South San Francisco, California 94080.
  • Minamisawa S; Department of Life Science and Medical Bioscience, Waseda University, 3-4-1 Okubo, Shinjuku-ku, 169-8555, Japan; Department of Cell Physiology, Jikei University, 25-8, Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan.
  • Wang Y; Departments of Anesthesiology, Physiology, and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, California 90095. Electronic address: yibinwang@mednet.ucla.edu.
J Biol Chem ; 292(31): 12787-12800, 2017 08 04.
Article en En | MEDLINE | ID: mdl-28637870
Stress-induced p38 mitogen-activated protein kinase (MAPK) activity is implicated in pathological remodeling in the heart. For example, constitutive p38 MAPK activation in cardiomyocytes induces pathological features, including myocyte hypertrophy, apoptosis, contractile dysfunction, and fetal gene expression. However, the physiological function of cardiomyocyte p38 MAPK activity in beneficial compensatory vascular remodeling is unclear. This report investigated the functional role and the underlying mechanisms of cardiomyocyte p38 MAPK activity in cardiac remodeling induced by chronic stress. Using both in vitro and in vivo model systems, we found that p38 MAPK activity is required for hypoxia-induced pro-angiogenic activity from cardiomyocytes and that p38 MAPK activation in cardiomyocyte is sufficient to promote paracrine signaling-mediated, pro-angiogenic activity. We further demonstrate that VEGF is a paracrine factor responsible for the p38 MAPK-mediated pro-angiogenic activity from cardiomyocytes and that p38 MAPK pathway activation is sufficient for inducing VEGF secretion from cardiomyocytes in an Sp1-dependent manner. More significantly, cardiomyocyte-specific inactivation of p38α in mouse heart impaired compensatory angiogenesis after pressure overload and promoted early onset of heart failure. In summary, p38αMAPK has a critical role in the cross-talk between cardiomyocytes and vasculature by regulating stress-induced VEGF expression and secretion in cardiomyocytes. We conclude that as part of a stress-induced signaling pathway, p38 MAPK activity significantly contributes to both pathological and compensatory remodeling in the heart.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Endotelio Vascular / Isquemia Miocárdica / Miocitos Cardíacos / Proteína Quinasa 14 Activada por Mitógenos / Revascularización Miocárdica Tipo de estudio: Prognostic_studies Idioma: En Revista: J Biol Chem Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Endotelio Vascular / Isquemia Miocárdica / Miocitos Cardíacos / Proteína Quinasa 14 Activada por Mitógenos / Revascularización Miocárdica Tipo de estudio: Prognostic_studies Idioma: En Revista: J Biol Chem Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos