β-adrenergic pathways in human heart failure

Abstract

β-adrenergic receptor activation plays an important role in the progression of human heart failure and the treatment of patients with β-blockers has greatly improved the outcome of the disease. However, heart failure still is one of the leading causes of death in various countries and there is an imperative need for additional targets for the treatment of the disease. Recent studies by various groups have analyzed the downstream signaling pathways activated in response to β-adrenergic stimulation that have the potential to become important targets for future treatments of heart failure. This review focuses on the significance of these pathways in the pathophysiology of heart failure in response to β-adrenergic stimulation. More specifically the roles of PDE3, phosphorylation of phospholamban, and CaMKII activation are extensively discussed.

Keywords::

• β-adrenergic
• CaMKII
• cAMP
• fetal gene program
• PDE3
• phospholamban
• PKA PP1
• receptors