{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Androgen‐dependent tissue factor pathway inhibitor regulating protein (ADTRP) is a multi‐span transmembrane protein that plays diverse roles in vascular homeostasis, lipid metabolism, and cell survival. Its expression in endothelial cells is up‐regulated by androgen via direct binding of the androgen receptor to a half androgen response element within its promoter, thereby enhancing tissue factor pathway inhibitor (TFPI) mRNA levels and anticoagulant activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition to modulating TFPI and thus contributing to the protection of the endothelium from thrombotic events, ADTRP functions as an atypical transmembrane threonine hydrolase that specifically hydrolyzes bioactive fatty acid esters of hydroxy fatty acids (FAHFAs), suggesting an important role in bioactive lipid metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n ADTRP has further been implicated in the regulation of endothelial cell function by modulating intracellular signaling cascades. For example, ADTRP positively regulates the expression of PIK3R3, thereby activating the AKT pathway, which in turn up‐regulates the expression of MIA3/TANGO1 – a process that is critical for maintaining vascular integrity and mitigating atherosclerotic events"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ">."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, mechanistic studies have revealed that ADTRP can control TFPI expression at the transcriptional level via a POU1F1‑dependent pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its direct roles in coagulation and lipid hydrolysis, ADTRP is involved in processes that regulate vascular development and stability. Reduced ADTRP expression is linked to vascular malformations, increased endothelial permeability, and aberrant inflammatory responses that contribute to the risk of coronary artery disease (CAD) and myocardial infarction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": " Furthermore, recent findings indicate that oxidized low‐density lipoprotein (ox‐LDL) can induce ADTRP expression, and that ADTRP participates in a positive regulatory loop with LDL receptors (LDLR, CD36, LOX‐1) via NF‑κB and AKT pathways, reinforcing its protective role against atherosclerosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, comprehensive reviews emphasize ADTRP’s multifaceted functions – as an androgen‐responsive regulator of coagulation, as an enzyme mediating bioactive lipid catabolism, and as a modulator of signaling cascades that influence endothelial proliferation, migration, and apoptosis – all of which underpin its emerging role in the pathogenesis of atherosclerosis, CAD, obesity, and metabolic disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Cristina Lupu, Hua Zhu, Narcis I Popescu, et al. 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