{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:40:59Z","timestamp":1793400059477,"version":"4.5.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Currently, chronic immune rejection of bioprosthetic heart valves (BHVs) is considered among the key players in the development of structural valve degeneration (SVD). However, the relative contribution of leukocyte infiltration and cyclic mechanical loading into the SVD in bioprosthetic mitral valves (BMVs) and bioprosthetic tricuspid valves (BTVs, experiencing lower hemodynamic load due to the right heart\u2019s pressure environment) remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here we performed an investigation of BMVs and BTVs which have been pairwise-excised from 4 patients during the BHV replacement because of BMV failure. The amount of valvular calcification was measured by multislice computed tomography and quantified using Pydicom script. Immune cell infiltration and lipid deposition in sectioned leaflets were evaluated by hematoxylin and eosin and Oil Red O staining, respectively; the semi-quantitative analysis of whole slide images was conducted by QuPath and Fiji software. In addition, we conducted an ultrastructural examination of BHVs by backscattered scanning electron microscopy after epoxy resin embedding (EM-BSEM technique).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>All BMVs had a significant extent of lipid deposition, hemorrhages, and tears, which eventually led to its mechanical incompetence. Strikingly, BMVs had less amount of immune cell infiltration as compared with BTVs. These results indicate that mechanical fatigue prevails over immune cell infiltration in driving the development of SVD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1652294","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T04:12:59Z","timestamp":1756872779000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Structural valve deterioration is primarily caused by cyclic fatigue but not immune rejection"],"prefix":"10.3389","volume":"16","author":[{"given":"Alexander E.","family":"Kostyunin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana V.","family":"Glushkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny A.","family":"Ovcharenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel S.","family":"Onischenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirill Yu.","family":"Klyshnikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana N.","family":"Akentieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo A.","family":"Bogdanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav A.","family":"Koshelev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander N.","family":"Stasev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton A.","family":"Khromov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton G.","family":"Kutikhin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart disease and stroke statistics-2020 update: a report from the American Heart Association","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00570-z","article-title":"Global epidemiology of valvular heart disease","volume":"18","author":"Coffey","year":"2021","journal-title":"Nat Rev Cardiol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e72","DOI":"10.1161\/CIR.0000000000000923","article-title":"ACC\/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology\/American Heart Association Joint Committee on clinical practice guidelines","volume":"143","author":"Otto","year":"2020","journal-title":"Circulation"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx141","article-title":"Mechanical versus bioprosthetic aortic valve replacement","volume":"38","author":"Head","year":"2017","journal-title":"Eur Heart J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.778886","article-title":"Prosthetic heart valves: selection of the optimal prosthesis and long-term management","volume":"119","author":"Pibarot","year":"2009","journal-title":"Circulation."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2147\/PPA.S16420","article-title":"Cardiac crossroads: deciding between mechanical or bioprosthetic heart valve replacement","volume":"17","author":"Tillquist","year":"2011","journal-title":"Patient Prefer Adherence."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx303","article-title":"Standardized definitions of structural deterioration and valve failure in assessing long-term durability of transcatheter and surgical aortic bioprosthetic valves: a consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) endorsed by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)","volume":"38","author":"Capodanno","year":"2017","journal-title":"Eur Heart J"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.030729","article-title":"VIVID (Valve in Valve International Data) Investigators. 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