An overview of alamadine/MrgD signaling and its role in cardiomyocytes

Abstract

The renin-angiotensin system (RAS) is a classical hormonal system involved in a myriad of cardiovascular functions. This system is composed of many different peptides that act in the heart through different receptors. One of the most important of these peptides is Angiotensin II, which in pathological conditions triggers a set of actions that lead to heart failure. On the other hand, another RAS peptide, Angiotensin-(1-7) is well known to develop powerful therapeutic effects in many forms of cardiac diseases. In the last decade, two new components of RAS were described, the heptapeptide Alamandine and its receptor, the Mas-related G protein-coupled receptor member D (MrgD). Since then, great effort was made to characterize their physiological and pathological function in the heart. In this review, we summarize the latest insights about the actions of Alamandine/MrgD axis in the heart, with particular emphasis in the cardiomyocyte. More specifically, we focused on their anti-hypertrophic and contractility effects, and the related molecular events activated in the cardiomyocyte.

Alternative Renin-Angiotensin System

“…An atypical signaling of peptide ligands (neuropeptide FF and angiotensin fragments including Ang-[1-7]) through Mas (G-protein-independent signaling) was reported in a study focusing Ca2 + influx in MAS -transfected HEK293 cells. 85 Future studies are needed to clarify the results of these in vitro studies which were not supported by other findings using other cell types 86–88 or even similar cells. 75,89 Despite these discrepancies, most studies support a direct activation of Mas by Ang-(1-7), but the distinct response of a specific cell on Ang-(1-7) stimulation may depend on its expression of additional peptide receptors besides Mas.…”