{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T03:18:48Z","timestamp":1789269528007,"version":"build-2803163510"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,1,3]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Whereas the risk factors for structural valve degeneration (SVD) of glutaraldehyde\u2010treated bioprosthetic heart valves (BHVs) are well studied, those responsible for the failure of BHVs fixed with alternative next\u2010generation chemicals remain largely unknown. This study aimed to investigate the reasons behind the development of SVD in ethylene glycol diglycidyl ether\u2013treated BHVs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Ten ethylene glycol diglycidyl ether\u2013treated BHVs excised because of SVD, and 5 calcified aortic valves (AVs) replaced with BHVs because of calcific AV disease were collected and their proteomic profile was deciphered. Then, BHVs and AVs were interrogated for immune cell infiltration, microbial contamination, distribution of matrix\u2010degrading enzymes and their tissue inhibitors, lipid deposition, and calcification. In contrast with dysfunctional AVs, failing BHVs suffered from complement\u2010driven neutrophil invasion, excessive proteolysis, unwanted coagulation, and lipid deposition. Neutrophil infiltration was triggered by an asymptomatic bacterial colonization of the prosthetic tissue. Neutrophil elastase, myeloblastin\/proteinase 3, cathepsin G, and matrix metalloproteinases (MMPs; neutrophil\u2010derived MMP\u20108 and plasma\u2010derived MMP\u20109), were significantly overexpressed, while tissue inhibitors of metalloproteinases 1\/2 were downregulated in the BHVs as compared with AVs, together indicative of unbalanced proteolysis in the failing BHVs. As opposed to other proteases, MMP\u20109 was mostly expressed in the disorganized prosthetic extracellular matrix, suggesting plasma\u2010derived proteases as the primary culprit of SVD in ethylene glycol diglycidyl ether\u2013treated BHVs. Hence, hemodynamic stress and progressive accumulation of proteases led to the extracellular matrix degeneration and dystrophic calcification, ultimately resulting in SVD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Neutrophil\u2010 and plasma\u2010derived proteases are responsible for the loss of BHV mechanical competence and need to be thwarted to prevent SVD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.028215","type":"journal-article","created":{"date-parts":[[2022,12,24]],"date-time":"2022-12-24T10:35:49Z","timestamp":1671878149000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Proteolytic Degradation Is a Major Contributor to Bioprosthetic Heart Valve 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