{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe MAS1 receptor is a critical element of the ACE2/Ang-(1-7)/MAS1 axis that counterbalances the traditional ACE/Ang II/AT1 receptor pathway. Activation of MAS1 by Ang-(1-7) triggers classical G protein–coupled signaling—including Gq/phospholipase C activation, intracellular calcium mobilization, and nitric oxide release—which underlies robust vasodilatory, anti‐inflammatory, antifibrotic, and antiproliferative effects in the cardiovascular system, myocardium, kidneys, pulmonary tissue, and even valve structures. Such signaling has been shown to improve coronary blood flow, alleviate myocardial ischemia–reperfusion injury, inhibit pathologic remodeling processes (as in calcific aortic stenosis and benign prostatic hyperplasia), and enhance endothelial barrier function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond vascular regulation, MAS1 signaling exerts significant control over cell growth, metabolic homeostasis, and malignant behavior. In various cancer models—including those of breast, colon, and hepatocellular origin—Ang-(1-7)/MAS1 activation inhibits tumor proliferation, migration, and invasion by modulating calcium entry and downstream MAPK as well as NF‑κB pathways. In adipose tissue, MAS1 engagement promotes adipogenesis and enhances thermogenic gene expression via PI3K/Akt activation, thereby supporting improved metabolic regulation. These multifaceted actions, combined with interactions with other angiotensin receptors, underscore the therapeutic potential of targeting MAS1 in oncological and metabolic disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMAS1 receptor expression is also dynamically regulated in reproductive tissues, where it contributes to the modulation of steroidogenesis, endometrial function, and overall fertility. In the ovary and endometrium, MAS1 coordinates with other renin–angiotensin system components to regulate cyclic hormonal changes and maintain tissue homeostasis. Conversely, altered MAS1 expression has been associated with reproductive pathologies such as endometriosis, suggesting that its proper function is crucial for both normal reproductive physiology and repair processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "32", "end_ref": "35"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Robson Augusto Souza Santos, Walkyria Oliveira Sampaio, Andreia C Alzamora, et al. 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