The Adrenergic Pathway and Heart Failure
| Autor: | W. J. Koch, J. R. Keys |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Sympathetic nervous system
Sympathetic Nervous System Adrenergic receptor Cardiac Output Low Adrenergic Mice Transgenic Pharmacology Mice Endocrinology GTP-Binding Proteins medicine Animals Humans Mice Knockout G protein-coupled receptor kinase biology Beta adrenergic receptor kinase Heart medicine.disease Cyclic AMP-Dependent Protein Kinases Receptors Adrenergic medicine.anatomical_structure beta-Adrenergic Receptor Kinases Heart failure Genetically Engineered Mouse Hypertension Knockout mouse biology.protein Neuroscience Signal Transduction |
| Zdroj: | Recent Progress in Hormone Research. 59:13-30 |
| ISSN: | 0079-9963 |
| DOI: | 10.1210/rp.59.1.13 |
| Popis: | Heart failure represents the endpoint to many triggering cardiovascular pathologies. However, there are molecular and biochemical features that remain common to the failing heart, despite the varying etiologies. Principal among these is heightened activation of the sympathetic nervous system and associated enhancement of adrenergic signaling pathways via the catecholamines, norepinephrine and epinephrine. During heart failure, several hallmark alterations in the adrenergic system contribute to loss of cardiac function. To specifically study these changes in a physiologically relevant setting, we and others have utilized advances in genetically engineered mouse technology. This chapter will discuss the many transgenic and knockout mouse models that have been developed to study the adrenergic system in the normal and failing heart. These models include genetically manipulated alterations of adrenergic receptors, linked heterotrimeric G proteins, and the regulatory G protein-coupled receptor kinases (GRKs). Among the more-interesting information gained from these models is the finding that inhibition of a particular GRK - GRK2 or beta adrenergic receptor kinase 1 (betaARK1) - is a potential novel therapeutic strategy to improve function in the setting of heart failure. Furthermore, we will discuss recent transgenic research that proposes an important role for hypertension in the development of heart failure. Overall, genetically engineered mouse models pertaining to this critical myocardial signaling system have provided novel insight into heart function under normal conditions and during states of dysfunction and failure. |
| Databáze: | OpenAIRE |
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