Molecular mechanism of mechanical stress-induced cardiac hypertrophy.
Mechanical stress is a major cause of cardiac hypertrophy. Although the mechanisms by which mechanical load induces cardiomyocyte hypertrophy have long been a subject of great interest for cardiologists, the lack of a good in vitro system has hampered the understanding of the biochemical mechanisms. For these past several years, however, an in vitro neonatal cardiocyte culture system has made it possible to examine the biochemical basis for the signal transduction of mechanical stress. Passive stretch of cardiac myocytes cultured on silicone membranes activates phosphorylation cascades of many protein kinases including protein kinase C, Raf-1 kinase and extracellular signal regulated kinases, and induces the expression of specific genes as well as an increase in protein synthesis. During that process, the secretion and production of vasoactive peptides such as angiotensin II and endothelin, are increased and they play critical roles in the induction of these hypertrophic responses. Although the involvement of vasoactive peptides in the development of cardiac hypertrophy is clinically important, the "mechanoreceptor" which receives the mechanical stress and converts it into intracellular biochemical signals remained unknown. We have recently obtained evidence suggesting that ion channels and integrins may be the "mechanoreceptor", the activation of which leads to cardiac hypertrophy.
Komuro
I
I
Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, Japan.
D000818:Animals; D006332:Cardiomegaly / Q000209:etiology*; D006801:Humans; D008465:Mechanoreceptors / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical
D018377:Neurotransmitter Agents; D011494:Protein Kinases