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Notable successes include the treatment of pulmonary hypertension with endothelin receptor antagonists, and the treatment of heart failure and chronic kidney disease with SGLT-2 inhibitors. With distinct and complementary mechanisms, in this review, we explore the logic of combination therapy for a number of diseases which have endothelial dysfunction at their heart.<\/jats:p>","DOI":"10.1042\/cs20240605","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T06:07:55Z","timestamp":1717567675000},"page":"687-697","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Targeting the endothelium by combining endothelin-1 antagonism and SGLT-2 inhibition: better together?"],"prefix":"10.1042","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2978-1886","authenticated-orcid":false,"given":"Phil","family":"Ambery","sequence":"first","affiliation":[{"name":"1Clinical Late Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter\u00a0J.","family":"Greasley","sequence":"additional","affiliation":[{"name":"2Early Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert\u00a0I.","family":"Menzies","sequence":"additional","affiliation":[{"name":"3Bioscience Renal, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Brynne","sequence":"additional","affiliation":[{"name":"4Information Practice Late Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spoorthy","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"5Department of Clinical Pharmacology and Therapeutics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB20QQ, U.K."},{"name":"6Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Oscarsson","sequence":"additional","affiliation":[{"name":"1Clinical Late Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2096-3117","authenticated-orcid":false,"given":"Anthony\u00a0P.","family":"Davenport","sequence":"additional","affiliation":[{"name":"6Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke\u2019s Hospital, Cambridge, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"key":"2024061011355839400_B1","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1161\/HYPERTENSIONAHA.119.12105","article-title":"Endothelin: 30 years from discovery to therapy","volume":"74","author":"Barton","year":"2019","journal-title":"Hypertension"},{"key":"2024061011355839400_B2","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1111\/j.1476-5381.2012.02194.x","article-title":"Aldosterone affects blood flow and vascular tone regulated by endothelium-derived NO: therapeutic implications","volume":"168","author":"Toda","year":"2013","journal-title":"Br. 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