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The Molecular Mechanism of Cardiac Hypertrophy and Failure
Author(s) -
YAMAZAKI TSUTOMU,
KOMURO ISSEI,
SHIOJIMA ICHIRO,
YAZAKI YOSHIO
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb09223.x
Subject(s) - mechanism (biology) , cardiac hypertrophy , muscle hypertrophy , heart failure , chemistry , cardiology , medicine , physics , quantum mechanics
A bstract : Mechanical stretch induced by high blood pressure is an initial factor leading to cardiac hypertrophy. In an in vivo study, an angiotensin II (AngII) type 1 receptor antagonist TCV116 reduced left ventricular (LV) weight, LV wall thickness, transverse myocyte diameter, relative amount of V3 myosin heavy chain, and interstitial fibrosis, while treatment with hydralazine did not. In an in vitro study using cultured cardiomyocytes, mechanical stretch activated second messengers such as mitogen‐activated protein (MAP) kinase, followed by increased protein synthesis. Additionally, in the stretch‐conditioned medium AngII and endothelin‐1 concentrations were increased. Furthermore, the Na + /H + exchanger activated by mechanical stretch modulated the hypertrophic responses of cardiomyocytes. The pathways leading to MAP kinase activation differed between cell types. In cardiac fibroblasts AngII activated MAP kinase via Gβγ subunit of Gi, Src, Shc, Grb2, and Ras, whereas Gq and protein kinase C were critical in cardiomyocytes.