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Less than 1% of total body phosphate is found in the circulation and extracellular space, and its regulation involves multiple organ cross talk and hormones to coordinate absorption from the small intestine and excretion by the kidneys. For phosphate to be regulated, it must be sensed. While mostly enigmatic, various phosphate sensors have been elucidated in recent years. Phosphate in the circulation can be buffered, either through regulated exchange between extracellular and cellular spaces or through chelation by circulating proteins (ie, fetuin-A) to form calciprotein particles, which in themselves serve a function for bulk mineral transport and signaling. Either through direct signaling or through mediators like hormones, calciprotein particles, or calcifying extracellular vesicles, phosphate can induce various cardiovascular disease pathologies: most notably, ectopic cardiovascular calcification but also left ventricular hypertrophy, as well as bone and kidney diseases, which then propagate phosphate dysregulation further. Therapies targeting phosphate have mostly focused on intestinal binding, of which appreciation and understanding of paracellular transport has greatly advanced the field. However, pharmacotherapies that target cardiovascular consequences of phosphate directly, such as vascular calcification, are still an area of great unmet medical need.<\/jats:p>","DOI":"10.1161\/atvbaha.123.319198","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T10:00:37Z","timestamp":1704967237000},"page":"584-602","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":58,"title":["Phosphate in Cardiovascular Disease: From New Insights Into Molecular Mechanisms to Clinical Implications"],"prefix":"10.1161","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6431-5077","authenticated-orcid":true,"given":"Mandy E.","family":"Turner","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences (M.E.T., E.A.), Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, 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