ANTI-INFLAMMATORY RESPONSE OF THE ANGIOTENSIN-(1-7) MAS RECEPTOR: DIALOGUE WITH OTHER RECEPTORS

GIRONACCI MM

Congreso; JOINT MEETING SAIC SAI&FAIC SAFIS 2022; 2023

Inflammation has been shown to play an important role in the mechanisms involved in the pathogenesis of hypertension. Different subpopulations of cells involved in innate and adaptive immune responses, such as monocyte/macrophages and dendritic cells on one hand and B and T lymphocytes on the other hand, play roles leading to vascular injury in hypertension. The components of the renin-angiotensin system play an important role in inflammation. While it is well established that angiotensin (Ang) II elicits proinflammatory properties in a range of target organs, Ang-(1-7), a component of this system synthetized mainly by angiotensin-converting enzyme 2 from Ang II, counter-regulates Ang II effects. Ang-(1-7) exerts its actions through Mas receptor (MasR). Activation of ACE2/Ang-(1–7)/MasR axis has been described to display anti-inflammatory actions in several experimental models, including ischemic stroke, atherosclerosis, pulmonary fibrosis, acute lung injury and arthritis. MasR belongs to the G protein-coupled receptors (GPCRs) family. Although GPCRs are able to operate as monomers, there is increasing evidence about the ability of GPCRs to form and function as heterodimers/heteromers that exhibit distinct pharmacological, trafficking and functional properties as compared to their parent monomeric or homodimeric/homomeric GPCRs. Efforts have focused over the past two decades on the identification of GPCR complexes as well as on their signaling properties. In our lab we have been investigating how the anti-inflammatory properties of MasR are influenced by interaction with others GPCRs. GPCRs heteromerization not only brings forth a plethora of drug target combinations, but also gives an opportunity to carefully tweak the structure and function of one or more GPCRs involved in the complex, with the final goal of improving therapeutic strategies.