β-adrenergic signaling in chronic heart failure -: Friend or foe?

In chronic heart failure, a number of compensatory mechanisms are activated in order to maintain circulation and thus supply of the body with Wood and oxygen. One important mechanism is the activation of the sympathetic nervous system, resulting in increased beta-adrenergic signaling. This leads to both adaptive and pathological processes within the cell, including a desensitization of the beta-adrenergic signal transduction cascade, the induction of hypertrophy, apoptosis and necrosis. It is currently a matter of debate whether a desensitization of the beta-adrenergic signal transduction cascade is adaptive or maladaptive. In other words, it is not entirely clear whether in heart failure, decreased beta-adrenergic signaling due to desensitization of the signaling cascade per se is a cause for cardiac dysfunction. In order to elucidate this issue, this review will focus on the consequences of increased beta-adrenergic signaling, investigated by selective overexpression of distinct cascade components in mouse models. Furthermore, the impact of partial and inverse agomism of beta-blockers on beta-adrenergic signaling in human myocardium in vitro as well as in vivo in the clinical situation in patients with heart failure is highlighted. It is discussed whether the fact that not all beta-blockers improve survival in heart failure patients may be due to their respective degree of inverse agonism.