Altered heart cytokine profile and action potential modulation in cardiomyocytes from Mas-deficient mice

Coutinho, Danielle Carvalho Oliveira; Joviano-Santos, Julliane V.; Santos-Miranda, Artur; Martins-Júnior, Paulo Antônio; Da Silva, Analina; Santos, Robson Augusto Souza; Ferreira, Anderson José

Altered heart cytokine profile and action potential modulation in cardiomyocytes from Mas-deficient mice

2022

The renin-angiotensin system (RAS) is a key hormonal system. In recent years, the functional analysis of the novel axis of the RAS (ACE2/Ang-(1–7)/Mas receptor) revealed that its activation can become protective against several pathologies, including cardiovascular diseases. Mas knockout mice (Mas-KO) represent an important tool for new investigations. Indeed, extensive biological research has focused on investigating the functional implications of Mas receptor deletion. However, although the Mas receptor was identified in neonatal cardiomyocytes and also in adult ventricular myocytes, only few reports have explored the Ang-(1–7)/Mas signaling directly in cardiomyocytes to date. This study investigated the implication of Mas receptor knockout to the cytokine profile, energy metabolism, and electrical properties of mice-isolated cardiomyocytes. Here, we demonstrated that Mas-KO mice have modulation in some cytokines, such as G-CSF, IL-6, IL-10, and VEGF in the left ventricle. This model also presents increased mitochondrial number in cardiomyocytes and a reduction in the myocyte diameter. Finally, Mas-KO cardiomyocytes have altered action potential modulation after diazoxide challenge. Such electrical finding was different from the data showed for the TGR(A1-7)3292 (TGR) model, which overexpresses Ang-(1–7) in the plasma by 4.5, used by us as a control. Collectively, our findings exemplify the importance of understanding the ACE2/Ang-(1–7)/Mas pathway in cardiomyocytes and heart tissue. The Mas-KO mice model can be considered an important tool for new RAS investigations.

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