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Signals for cardiac muscle hypertrophy in hypertension
1Veterans Administration Medical Center, Cardiology Section, Charleston, SC 29403.
Insights
Hypertension can cause cardiac hypertrophy, a compensatory increase in heart mass. Understanding the factors influencing this growth is crucial for preventing heart failure.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
Background:
- Hypertension leads to increased arterial pressure and cardiac mass.
- Untreated cardiac hypertrophy can progress to decompensated congestive heart failure.
- Factors initiating and maintaining cardiac hypertrophy are of significant research interest.
Purpose of the Study:
- To investigate the signals that induce and sustain cardiac hypertrophy.
- To understand the dynamic regulation of cardiac structure and function by the loading environment.
- To elucidate cellular signaling pathways involved in hypertrophic cardiac growth.
Main Methods:
- Analysis of hemodynamic, hormonal, and genetic factors influencing cardiac hypertrophy.
- In vitro models to study cellular pathways.
- Examination of protein kinase C activation, cyclic AMP formation, and ion fluxes.
Main Results:
- Cardiac mass changes in parallel with cardiac load, returning to normal when load normalizes.
- Growth-promoting hormones (insulin, thyroxine) play a permissive role.
- Studied pathways (PKC, cAMP, ion fluxes) stimulate protein synthesis necessary for growth.
Conclusions:
- Cardiac structure and function are dynamically regulated by cardiocyte loading.
- Vasoconstriction-promoting hormones and genetic factors modulate adaptive responses.
- Cellular signaling pathways are key to transducing physical stimuli into hypertrophic growth.
Abstract:
Hypertension is associated with a rise in arterial pressure and a compensatory increase in cardiac mass, which if not treated effectively, progresses to decompensated congestive heart failure. This decompensation of an initially compensatory hypertrophy has intensified interest in the factors that initiate and maintain the development of cardiac hypertrophy. The potential signals that induce the development of cardiac hypertrophy are grouped as hemodynamic, growth-promoting hormonal, vasoconstriction-promoting hormonal, and genetic factors. Growth-promoting hormones such as insulin and thyroxine appear to play a permissive, but essential, role in the development and maintenance of cardiac hypertrophy. However, changes in cardiac load, both above and below normal, result in parallel changes in cardiac mass, which will return to normal when a normal load is restored. This adaptive response of the myocardium in direct response to elevated and depressed loads demonstrates that cardiac structure, composition, and function are not fixed postneonatal cardiac properties, but instead are regulated dynamically by the cardiocyte loading environment. This adaptive response is subject to modulation by vasoconstriction-promoting hormones and genetic factors. The current thrust in this research area is to elucidate the cellular signals that transduce the physical stimulus for hypertrophy into biochemical events underlying hypertrophic cardiac growth. To remove complex systemic interactions in vivo from the experimental paradigm, several in vitro models have been used to examine three general, but distinct, cellular pathways involving protein kinase C activation, cyclic AMP formation, and increased ion fluxes. Each pathway demonstrated a stimulatory effect on general protein synthesis, which is necessary for growth in all cells.(ABSTRACT TRUNCATED AT 250 WORDS)