title: [Molecular mechanism of cardiac hypertrophy and dysfunction].
abstract: We examined the signal transduction pathway for the development of cardiac hypertrophy induced by high blood pressure. The activities of Raf-1 kinase (Raf-1), mitogen-activated protein kinase kinase (MAPKK), MAP kinases (MAPKs) and 90-kDa ribosomal S6 kinase (p90rsk) was examined by passively stretching neonatal rat cardiomyocytes in vitro. Mechanical stretch activated these protein kinases transiently and sequentially: the maximal activation of Raf-1, MAPKK, MAPKs and p90rsk was observed at 2 minutes, 5 minutes, 8 minutes and 10 approximately 30 minutes, respectively. Both angiotensin II (AngII) and endothelin-1 (ET-1) were constitutively secreted from cultured cardiomyocytes, and a significant increase in the concentration was recognized in the culture medium of cardiomyocytes within 10 minutes after stretch. ET-1 mRNA levels were also increased in cardiomyocytes at 30 minutes after stretch. Moreover, ET-1 and AngII synergistically activated Raf-1 and MAPKs in cultured cardiomyocytes. In conclusion, mechanical stretch stimulates secretion and production of AngII and ET-1 in cultured cardiomyocytes, and both vasoconstrictive peptides may play an important role in mechanical stress (high blood pressure)-induced cardiac hypertrophy.
authors.affiliation: Health Service Center, University of Tokyo.
authors.forename: T
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000209:etiology*; D019332:Endothelin-1 / Q000502:physiology; D006333:Heart Failure / Q000209:etiology*; D006801:Humans; D006973:Hypertension / Q000150:complications*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013314:Stress, Mechanical
chemical_list: D019332:Endothelin-1; D000804:Angiotensin II; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases