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Its prevalence is rising due to ageing populations and the increasing incidence of diseases such as chronic kidney disease, obesity, and diabetes that are associated with elevated cardiovascular risk. Despite currently available treatments, there remains a huge burden of cardiovascular disease-associated morbidity for patients and healthcare systems, and newer treatments are needed. The apelin system, comprising the apelin receptor and its two endogenous ligands apelin and elabela, is a broad regulator of physiology that opposes the actions of the renin-angiotensin and vasopressin systems. Activation of the apelin receptor promotes endothelium-dependent vasodilatation and inotropy, lowers blood pressure, and promotes angiogenesis. The apelin system appears to protect against arrhythmias, inhibits thrombosis, and has broad anti-inflammatory and anti-fibrotic actions. It also promotes aqueous diuresis through direct and indirect (central) effects in the kidney. Thus, the apelin system offers therapeutic promise for a range of cardiovascular, kidney, and metabolic diseases. This review will discuss current cardiovascular disease targets of the apelin system and future clinical utility of apelin receptor agonism.<\/jats:p>","DOI":"10.1093\/cvr\/cvad171","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T17:48:55Z","timestamp":1699897735000},"page":"2683-2696","source":"Crossref","is-referenced-by-count":107,"title":["Targeting the apelin system for the treatment of cardiovascular diseases"],"prefix":"10.1093","volume":"119","author":[{"given":"Fiona A","family":"Chapman","sequence":"first","affiliation":[{"name":"BHF\/University of Edinburgh Centre for Cardiovascular Science, Queen\u2019s Medical Research Institute , Edinburgh , UK"},{"name":"Department of Renal Medicine, Royal Infirmary of Edinburgh , Edinburgh , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet J","family":"Maguire","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine and Immunotherapeutics, Addenbrooke\u2019s Centre for Clinical Investigation, University of Cambridge , Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7971-4628","authenticated-orcid":false,"given":"David E","family":"Newby","sequence":"additional","affiliation":[{"name":"BHF\/University of Edinburgh Centre for Cardiovascular Science, Queen\u2019s Medical Research Institute , Edinburgh , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2096-3117","authenticated-orcid":false,"given":"Anthony P","family":"Davenport","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, Royal Infirmary of Edinburgh , Edinburgh , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9128-6603","authenticated-orcid":false,"given":"Neeraj","family":"Dhaun","sequence":"additional","affiliation":[{"name":"BHF\/University of Edinburgh Centre for Cardiovascular Science, Queen\u2019s Medical Research Institute , Edinburgh , UK"},{"name":"Department of Renal Medicine, Royal Infirmary of Edinburgh , Edinburgh , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"key":"2023123018155964800_cvad171-B1","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors, 1990\u20132019: update from the GBD 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"2023123018155964800_cvad171-B2","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0140-6736(05)17741-1","article-title":"Global burden of hypertension: analysis of worldwide data","volume":"365","author":"Kearney","year":"2005","journal-title":"Lancet"},{"key":"2023123018155964800_cvad171-B3","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1097\/01.ASN.0000132474.50966.DA","article-title":"Endothelial dysfunction","volume":"15","author":"Endemann","year":"2004","journal-title":"J Am Soc Nephrol"},{"key":"2023123018155964800_cvad171-B4","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.pharmthera.2014.06.003","article-title":"Endothelial dysfunction in conduit arteries and in microcirculation. 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