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Aberrant serotonergic activity contributes to vascular pathology in multiple cardiovascular disease states, including hypertension, diabetes, metabolic syndrome and chronic myocardial ischemia. Serotonin also plays a vital role in postoperative vascular dysfunction after cardioplegic arrest with cardiopulmonary bypass (CP\/CPB). Perioperative microvascular dysfunction following CP\/CPB manifests as an increased propensity for vasospasm or vasoplegia, with different effects in different tissue beds (coronary, skeletal muscle, pulmonary and systemic microcirculations). Given the importance of serotonin as a modulator of vasogenic responses, we present a selected narrative survey of the current literature concerning the effects of altered serotonergic activity on vascular dysfunction in the context of CP\/CPB and other cardiometabolic diseases. This review begins with a discussion of normal serotonin biology and signaling pathways, then moves into disease-specific discussions covering five major areas of focus: metabolic syndrome, diabetes, hypertension, myocardial ischemia and CP\/CPB.<\/jats:p>","DOI":"10.3390\/cells15141265","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T10:12:53Z","timestamp":1784023973000},"page":"1265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Serotonin Signaling and Vascular Reactivity in Cardiometabolic Disease and Cardiac Surgery"],"prefix":"10.3390","volume":"15","author":[{"given":"Alexander","family":"Joseph","sequence":"first","affiliation":[{"name":"Rhode Island Hospital, Brown University Health, Warren Alpert Medical School, Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3142-3930","authenticated-orcid":false,"given":"Jared","family":"Hsu","sequence":"additional","affiliation":[{"name":"Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Han","sequence":"additional","affiliation":[{"name":"Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Kant","sequence":"additional","affiliation":[{"name":"Rhode Island Hospital, Brown University Health, Warren Alpert Medical School, Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2205-3229","authenticated-orcid":false,"given":"Lucian","family":"Lozonschi","sequence":"additional","affiliation":[{"name":"Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Sellke","sequence":"additional","affiliation":[{"name":"Rhode Island Hospital, Brown University Health, Warren Alpert Medical School, Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4762-7532","authenticated-orcid":false,"given":"Jun","family":"Feng","sequence":"additional","affiliation":[{"name":"Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/S0021-9258(18)57137-4","article-title":"Serum Vasoconstrictor (Serotonin)","volume":"176","author":"Rapport","year":"1948","journal-title":"J. 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