RESUMO
The renin-angiotensin (Ang) system (RAS) is a complex hormonal system present locally in several tissues such as cardiovascular organs. RAS deregulation through overactivation of the classical arm [Ang-converting enzyme (ACE)/Ang-II/Ang type 1 receptor (AT1R)] has been linked to the development of cardiovascular diseases and activation of endoplasmic reticulum (ER) stress pathways. The ER stress is a condition that, if unresolved, might lead to heart failure, atherosclerosis, hypertension, and endothelial dysfunction. Accumulated evidence has shown that the RAS modulates the UPR activation. Several studies reported increased ER stress markers in response to Ang-II treatment, in both in vivo and in vitro models. Evidence has also pointed that targeting the RAS classical arm through RAS blockers, gene silencing or genetic models leads to lower levels of ER stress markers. Few studies demonstrated protective effects of the counter-regulatory arm (ACE-2/Ang-(1-7)/Mas receptor) over ER stress. However, the crosstalk mechanisms between the arms of the RAS and ER stress remain unclear. In this review, we sought to explore the classical arm of the RAS as a key mechanism in UPR activation and to suggest a possible protective role of the counter-regulatory arm in mitigating ER stress.