{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:09:40Z","timestamp":1788772180570,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sapienza University","award":["AR1221816C74AE98"],"award-info":[{"award-number":["AR1221816C74AE98"]}]},{"award":["AR1221816C74AE98"],"award-info":[{"award-number":["AR1221816C74AE98"]}],"id":[{"id":"https:\/\/ror.org\/02be6w209","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Takotsubo syndrome (TTS) is an acute and reversible heart failure condition characterized by transitional left ventricular systolic dysfunction without obstructive coronary artery disease. Although sympathetic hyperactivation is considered a key pathogenic mechanism, the contribution of gut-derived endotoxemia and oxidative stress is still unclear. Lipopolysaccharide (LPS), an endotoxin of Gram-negative bacteria, may translocate from the gut into the bloodstream and increase oxidative stress through activation of NADPH oxidase 2 (NOX2), nitric oxide (NO) depletion and endothelial dysfunction. This study aimed to evaluate circulating LPS levels in TTS and investigate their association with NOX2 activation, oxidative stress, and endothelial dysfunction. Twenty consecutive patients with TTS and 20 age- and sex-matched healthy controls were included. Within 48 h of admission, fasting blood samples were collected to assess soluble NOX2-derived peptide (sNOX2-dp), hydrogen peroxide (H2O2), NO metabolites (NOx), LPS, and zonulin. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Compared with controls, TTS patients had significantly higher serum levels of sNOX2-dp, H2O2, LPS, and zonulin, lower NOx and impaired FMD. sNOX2-dp was positively correlated with LPS (Rs = 0.539, p &lt; 0.001) and zonulin (Rs = 0.331, p = 0.037) and inversely correlated with FMD (Rs = \u22120.462, p = 0.003). NOx correlated negatively with H2O2, zonulin and LPS. In multivariable analysis, LPS was the only independent predictor of FMD (\u03b2 = 0.498, SE = 0.126, p = 0.001) and sNOX2-dp (\u03b2 = \u22120.572, SE = 0.034 p &lt; 0.001); FMD (\u03b2 = \u22120.347, SE = 0.455, p = 0.005), H2O2 (\u03b2 = 0.445, SE = 0.155, p &lt; 0.001), and zonulin (\u03b2 = 0.298, SE = 2.309, p = 0.016) emerged as independent predictors of LPS (adjusted R2 = 0.585). TTS is associated with low-grade endotoxemia, NOX2-driven oxidative stress, reduced NO bioavailability, and endothelial dysfunction. The independent association between LPS and NOX2 activation supports a potential gut\u2013vascular axis in TTS pathophysiology.<\/jats:p>","DOI":"10.3390\/antiox15091124","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:07:06Z","timestamp":1788768426000},"page":"1124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low-Grade Endotoxemia Is Associated with NOX2-Mediated Oxidative Stress and Endothelial Dysfunction in Takotsubo Syndrome: A Cross-Sectional Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6542-6235","authenticated-orcid":false,"given":"Lorenzo","family":"Loffredo","sequence":"first","affiliation":[{"name":"Interdisciplinary Department of Well-Being, Health and Environmental Sustainability (BESSA), Sapienza University of Rome, 02100 Rieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9758-8482","authenticated-orcid":false,"given":"Enrico","family":"Maggio","sequence":"additional","affiliation":[{"name":"Department of Medical and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6266-3059","authenticated-orcid":false,"given":"Simona","family":"Bartimoccia","sequence":"additional","affiliation":[{"name":"Department of Medical and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Vito","family":"Cantisani","sequence":"additional","affiliation":[{"name":"Interdisciplinary Department of Well-Being, Health and Environmental Sustainability (BESSA), Sapienza University of Rome, 02100 Rieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Antonio","family":"Angeloni","sequence":"additional","affiliation":[{"name":"Interdisciplinary Department of Well-Being, Health and Environmental Sustainability (BESSA), Sapienza University of Rome, 02100 Rieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Aurora","family":"Paraninfi","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Intensive Cardiac Care Unit, A. Perrino Hospital, 72100 Brindisi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Paolo","family":"Ciacci","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Paolo Colombo Hospital, ASL ROMA 6, 00049 Velletri, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Simona","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Sandro Pertini Hospital, 00157 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4981-3374","authenticated-orcid":false,"given":"Federica","family":"Armeli","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5749-786X","authenticated-orcid":false,"given":"Ilaria Maria","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Surgical Specialty and Anaesthesiology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1190-9733","authenticated-orcid":false,"given":"Mariaelena","family":"Malvasi","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Giancarlo","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Surgical Specialties and Organ Transplantation, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2265-7455","authenticated-orcid":false,"given":"Pasquale","family":"Pignatelli","sequence":"additional","affiliation":[{"name":"Department of Medical and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6216-9595","authenticated-orcid":false,"given":"Roberto","family":"Carnevale","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Francesco","family":"Violi","sequence":"additional","affiliation":[{"name":"Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Francesco","family":"Barill\u00e0","sequence":"additional","affiliation":[{"name":"Health Sciences, UniCamillus-Saint Camillus International University, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4685-0898","authenticated-orcid":false,"given":"Gaetano","family":"Tanzilli","sequence":"additional","affiliation":[{"name":"Department of Medical and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.jjcc.2012.06.015","article-title":"Tako-tsubo cardiomyopathy: Clinical presentation and underlying mechanism","volume":"60","author":"Kurisu","year":"2012","journal-title":"J. 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