Related Experiment Videos
Catecholamines in cardiac hypertrophy
1Albert Einstein College of Medicine, Department of Medicine, Bronx, New York 10461, USA.
Insights
Catecholamines may influence cardiac hypertrophy, but mechanical factors are primary drivers in humans. Research explores alpha- and beta-adrenergic pathways in heart cell growth.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Cellular Biology
Background:
- Catecholamines are implicated in compensatory myocardial hypertrophy.
- The interplay between mechanical forces and catecholamines in cardiac growth is complex.
Purpose of the Study:
- To review the role of catecholamines in cardiac hypertrophy.
- To elucidate the signaling pathways involved in catecholamine-induced myocyte growth.
- To assess the clinical significance of catecholamines in human cardiac hypertrophy.
Main Methods:
- Review of experimental animal studies involving catecholamine infusions and mechanical stimulation.
- Analysis of in vitro studies using isolated myocytes and cell cultures.
- Examination of signaling pathways (Gq, MAP kinase) and transgenic mouse models.
- Evaluation of human observational data on cardiac hypertrophy.
Main Results:
- Chronic catecholamine infusion causes hypertrophy in animals, often confounded by mechanical factors.
- Mechanical activity alone can induce protein synthesis and cell growth in cardiac preparations.
- Alpha- and beta-adrenergic stimulation promote growth in neonatal and adult myocytes via distinct pathways.
- Human studies indicate mechanical factors are dominant in cardiac hypertrophy development and regression.
Conclusions:
- Mechanical factors are the predominant drivers of cardiac hypertrophy in humans.
- The precise quantitative role of catecholamines in human cardiac hypertrophy remains undetermined.
- Catecholamines may contribute to the transition from adaptive to maladaptive cardiac hypertrophy.
Abstract:
There has been intense interest in the roles catecholamines may play in compensatory myocardial hypertrophy. This article reviews the following: (1) chronic infusions of catecholamines in experimental animals result in cardiac hypertrophy, but in many of the studies mechanical factors have played a role; (2) experiments using isolated papillary muscles and isolated hearts, stretched isolated myocytes, and denervated hearts in vivo demonstrate that mechanical activity is sufficient to cause increased protein synthesis and cell growth; (3) in neonatal myocyte cell cultures, alpha-adrenergic agonists are powerful stimulants for protein synthesis and cell growth. Beta-adrenergic stimulation of nonmyocyte myocardial cells causes release of a factor that promotes protein synthesis in neonatal myocytes. Either alpha or beta stimulation, probably through different mechanisms, appears to have growth-promoting effects on isolated adult myocytes in culture; (4) alpha stimulation is transduced through the Gq pathway and its activation of phospholipase C, cleavage of phosphatidylinositol (4,5)-bisphosphate, and then further through the ras/raf, mitogen-activated protein (MAP) kinase system; (5) transgenic mice with upregulation of catecholamine-related systems have not clarified the independent role of either the alpha- or beta-adrenergic pathway; and (6) observations in humans suggest that mechanical factors predominate in the development and regression of cardiac hypertrophy. Humoral mechanisms, including catecholamines, may play a role, but their quantitative importance has not been determined. It is hypothesized that catecholamines may play a role in transition from the adaptive to the maladaptive state.