Anti-β1AR antibodies in dilated cardiomyopathy: Are these a new class of receptor agonists?

Abstract

See article by Tutor et al. [9] (pages 51−60) in this issue. Under physiological conditions, the β1-adrenergic receptor (β1AR) is the predominant βAR responsible for inotropic, chronotropic and lusitropic responses in the myocardium via the classical Gs/adenylyl cyclase/PKA pathway (reviewed in [1–3]). However, during the development of heart failure, sustained β1AR signalling may also lead to a number of adverse effects including cardiomyocyte hypertrophy and eventually apoptosis. It has become clear in recent years that alterations in the ERK and other MAP kinase signalling cascades play critical and complicated roles in the development of cardiac hypertrophy and the progression towards heart failure [4]. It is also clear that β-adrenergic receptors are key regulators of MAP kinase signalling, especially in the context of heart disease [5]. In a series of interesting papers, Martin Lohse and his colleagues have demonstrated a causal role in disease progression for autoimmune anti-β1AR antibodies found in patients with dilated cardiomyopathy (DCM, [6–8]). In an article in this issue of Cardiovascular Research , Tutor et al. [9] demonstrate a novel link between all of these observations by showing that anti-β1AR antibodies from several patients with DCM, but not control sera from healthy donors or sera from DCM patients that do not produce anti-β1AR, can activate the ERK signalling pathway in a manner distinct from receptor ligands. Their study has significant implications for basic receptor … *Tel.: +1 514 398 1398; fax: +1 514 398 6690. terence.hebert{at}mcgill.ca