{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe NPPA gene encodes the precursor of atrial natriuretic peptide (ANP), a key hormone in cardiovascular homeostasis. ANP is released from the heart in response to increased wall stress and acts on the kidney and vasculature to promote natriuresis, diuresis, and vasodilation, thereby lowering blood pressure and counteracting cardiac hypertrophy. Furthermore, common genetic variants at the NPPA (and the related NPPA‐NPPB) locus have been linked to increased circulating ANP levels, which in turn are associated with a favorable cardiometabolic profile, reduced risks of hypertension, stroke, and adverse remodeling of the myocardium. These observations highlight the role of NPPA in the regulation of salt–water balance, vascular tone, and cardiac structure and function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its well‐established physiological actions, genetic alterations and regulatory mechanisms affecting NPPA expression play an important role in disease susceptibility. Studies in families with early onset atrial fibrillation have identified frameshift mutations in NPPA that result in chimeric or extended ANP peptides with altered receptor interactions and proteolytic clearance. Investigations into the endogenous processing of pro‐ANP by cardiac serine proteases (such as corin) have demonstrated that precise proteolytic maturation is crucial for generating active ANP. Moreover, NPPA gene polymorphisms—including variants that affect microRNA binding and promoter methylation as well as genetic predisposition to conotruncal defects and even gastroschisis—underscore the importance of both genetic and epigenetic factors in modulating NPPA expression and peptide stability, thereby influencing arrhythmogenic risk and cardiac electrical properties."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "29"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its cardiovascular actions, ANP derived from NPPA is increasingly recognized for its roles in metabolic regulation, immunomodulation, and potential therapeutic applications. ANP has been shown to stimulate lipolysis and contribute to lipid mobilization during exercise, and its actions extend to improving insulin sensitivity and counteracting obesity‐related metabolic disturbances. In vascular and immune cells, ANP exerts anti‐inflammatory effects by modulating cytokine production and adhesion molecule expression, thereby promoting endothelial cell survival and shifting immune responses toward a reparative phenotype. Recent studies also point to innovative strategies using designer ANP analogues with enhanced and sustained biological actions for treating conditions such as heart failure, while associations with altered anxiety levels and endothelial permeability further expand the spectrum of NPPA‐related functions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "30", "end_ref": "44"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "David L Vesely "}, {"type": "b", "children": [{"type": "t", "text": "Atrial natriuretic peptide prohormone gene expression: hormones and diseases that upregulate its expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "IUBMB Life (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15216540212336"}], "href": "https://doi.org/10.1080/15216540212336"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12102171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12102171"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Peter Razeghi, Martin E Young, Jun Ying, et al. 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