Heart failure is a leading cause of morbidity and mortality in the elderly. During the initial phase of the disease, compensatory mechanisms to stimulate cardiac contractility are activated by catecholamines (neuro-hormones) through a hyperstimulation of B-adrenergic receptors. However, prolonged hyperstimulation becomes detrimental in heart failure leading to disease progression. G-protein coupled receptors are a superfamily of plasma membrane receptors which represent an important target of heart failure drug therapy. Despite the introduction of successful drug classes, such as beta-adrenergic receptor blockers and angiotensin-converting enzyme inhibitors, heart failure still poses an enormous challenge and there is an urgent need to develop innovative treatments counteracting mechanisms involved in heart failure, acting at the G protein coupled receptor level. In this review, we will focus on β1- and β2-adrenergic receptor function and the role of the G protein coupled receptor kinase 2, GRK2, in heart failure management in the elderly. In particular, we will discuss how GRK2 inhibition by βARKct or potential pharmacological inhibitors might represent a new therapeutic target in heart failure.
Age-related and heart failure-related beta-adrenergic receptor dysfunction: New therapeutic strategies for the treatment of cardiovascular diseases
Klara Komici;
2013-01-01
Abstract
Heart failure is a leading cause of morbidity and mortality in the elderly. During the initial phase of the disease, compensatory mechanisms to stimulate cardiac contractility are activated by catecholamines (neuro-hormones) through a hyperstimulation of B-adrenergic receptors. However, prolonged hyperstimulation becomes detrimental in heart failure leading to disease progression. G-protein coupled receptors are a superfamily of plasma membrane receptors which represent an important target of heart failure drug therapy. Despite the introduction of successful drug classes, such as beta-adrenergic receptor blockers and angiotensin-converting enzyme inhibitors, heart failure still poses an enormous challenge and there is an urgent need to develop innovative treatments counteracting mechanisms involved in heart failure, acting at the G protein coupled receptor level. In this review, we will focus on β1- and β2-adrenergic receptor function and the role of the G protein coupled receptor kinase 2, GRK2, in heart failure management in the elderly. In particular, we will discuss how GRK2 inhibition by βARKct or potential pharmacological inhibitors might represent a new therapeutic target in heart failure.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
