Cardiomyocyte α2-adrenergic receptor signaling counteracts intracellular Ca2+ overload and angiotensin-induced cardiac hypertrophy, representing a potential therapeutic target for heart failure.
Abstract—Aberrations in mechanisms of cardiac adaptation to catecholamine overflow can result in maladaptive cardiac hypertrophy and heart failure. Currently available heart failure therapies fall short of expectations, warranting their refinement via a paradigm shift from treatment of secondary factors of heart failure (neurohormonal activation, renal dysfunction, etc.) to direct heart targeting with the goal of improving the cardiac structure and function. We have detected expression of α2-adrenergic receptor (α2-AR) isoforms not only in adult cardiomyocytes, but also in the embryonic heart throughout its development from embryonic stem cells. In addition to known suppression of the sympathoadrenal system activity, α2-ARs play protective and adaptive roles in cardiomyocytes. This review analyzes cardiomyocyte α2-AR signaling, which counteracts intracellular Ca2+ overload and angiotensin-induced cardiac hypertrophy. We suppose that in heart failure-linked desensitization of these receptors, cardiac-specific cell- or gene-based therapies aimed at repairing or amplifying α2-AR signaling could offer prospects for a prevention of cardiac hypertrophy and heart failure.
Pimenov et al. (Sun,) conducted a review in Cardiac Hypertrophy and Heart Failure. α2-adrenergic receptor (α2-AR) targeted therapies was evaluated. Cardiomyocyte α2-adrenergic receptor signaling counteracts intracellular Ca2+ overload and angiotensin-induced cardiac hypertrophy, representing a potential therapeutic target for heart failure.