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Molecular and cellular mechanisms of mechanical stress-induced cardiac hypertrophy
Yunzeng Zou1, Hiroyuki Takano, Hiroshi Akazawa
1Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Inohana, Japan.
Insights
Mechanical stress causes cardiac hypertrophy, a precursor to heart failure. This review focuses on calcineurin
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Congestive heart failure is a significant clinical challenge.
- Cardiac hypertrophy precedes heart failure, necessitating mechanistic understanding.
- Hemodynamic overload (mechanical stress) is a primary driver of cardiac hypertrophy.
Purpose of the Study:
- To elucidate the mechanisms of cardiac hypertrophy induced by mechanical stress.
- To highlight the critical role of calcineurin in this process.
Main Methods:
- Review of existing literature on mechanical stress-induced cardiac hypertrophy.
- Focus on signaling pathways including protein kinases, gene expression, and protein synthesis.
- Emphasis on the involvement of calcineurin and CaMK.
Main Results:
- Mechanical stress triggers hypertrophic responses via phosphorylation cascades, gene expression, and protein synthesis.
- Vasoactive peptides like angiotensin II and endothelin-1 are upregulated and contribute to hypertrophy.
- Ca2+-dependent protein kinase (CaMK) and calcineurin are identified as key molecules in cardiac hypertrophy.
Conclusions:
- Calcineurin plays a crucial role in the development of cardiac hypertrophy.
- Understanding these mechanisms, particularly calcineurin's role, is vital for addressing heart failure.
Abstract:
Congestive heart failure is one of the major issues for cardiologists. Since cardiac hypertrophy deteriorates into heart failure, it is important to elucidate the mechanisms of cardiac hypertrophy. Hemodynamic overload, namely mechanical stress, is a major cause for cardiac hypertrophy. Mechanical stress induces various hypertrophic responses such as activation of phosphorylation cascades of many protein kinases, expression of specific genes and an increase in protein synthesis. During this process, secretion and production of vasoactive peptides such as angiotensin II and endothelin-1, are increased and play critical roles in the induction of these hypertrophic responses. Recently, a Ca2+ dependent protein kinase, CaMK, and a Ca2+ dependent protein phosphatase, calcineurin, have attracted great attention as critical molecules that induce cardiac hypertrophy. In this review, we described the mechanisms by which mechanical stress induces cardiac hypertrophy, especially focusing on the role of calcineurin in the development of cardiac hypertrophy.