Proteolytic Degradation Is a Major Contributor to Bioprosthetic Heart Valve Failure
Background Whereas the risk factors for structural valve degeneration (SVD) of glutaraldehyde‐treated bioprosthetic heart valves (BHVs) are well studied, those responsible for the failure of BHVs fixed with alternative next‐generation chemicals remain largely unknown. This study aimed to investigate...
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| Format: | Article |
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Wiley
2023-01-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.122.028215 |
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| author | Alexander E. Kostyunin Tatiana V. Glushkova Arseniy A. Lobov Evgeny A. Ovcharenko Bozhana R. Zainullina Leo A. Bogdanov Daria K. Shishkova Victoria E. Markova Maksim A. Asanov Rinat A. Mukhamadiyarov Elena A. Velikanova Tatiana N. Akentyeva Maria A. Rezvova Alexander N. Stasev Alexey V. Evtushenko Leonid S. Barbarash Anton G. Kutikhin |
| author_facet | Alexander E. Kostyunin Tatiana V. Glushkova Arseniy A. Lobov Evgeny A. Ovcharenko Bozhana R. Zainullina Leo A. Bogdanov Daria K. Shishkova Victoria E. Markova Maksim A. Asanov Rinat A. Mukhamadiyarov Elena A. Velikanova Tatiana N. Akentyeva Maria A. Rezvova Alexander N. Stasev Alexey V. Evtushenko Leonid S. Barbarash Anton G. Kutikhin |
| author_sort | Alexander E. Kostyunin |
| collection | DOAJ |
| description | Background Whereas the risk factors for structural valve degeneration (SVD) of glutaraldehyde‐treated bioprosthetic heart valves (BHVs) are well studied, those responsible for the failure of BHVs fixed with alternative next‐generation chemicals remain largely unknown. This study aimed to investigate the reasons behind the development of SVD in ethylene glycol diglycidyl ether–treated BHVs. Methods and Results Ten ethylene glycol diglycidyl ether–treated 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‐degrading enzymes and their tissue inhibitors, lipid deposition, and calcification. In contrast with dysfunctional AVs, failing BHVs suffered from complement‐driven 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‐derived MMP‐8 and plasma‐derived MMP‐9), 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‐9 was mostly expressed in the disorganized prosthetic extracellular matrix, suggesting plasma‐derived proteases as the primary culprit of SVD in ethylene glycol diglycidyl ether–treated BHVs. Hence, hemodynamic stress and progressive accumulation of proteases led to the extracellular matrix degeneration and dystrophic calcification, ultimately resulting in SVD. Conclusions Neutrophil‐ and plasma‐derived proteases are responsible for the loss of BHV mechanical competence and need to be thwarted to prevent SVD. |
| first_indexed | 2024-04-10T09:59:27Z |
| format | Article |
| id | doaj.art-ed68d24de8844d5994cf0c6ce895ff9f |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-10T09:59:27Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-ed68d24de8844d5994cf0c6ce895ff9f2023-02-16T10:55:33ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802023-01-0112110.1161/JAHA.122.028215Proteolytic Degradation Is a Major Contributor to Bioprosthetic Heart Valve FailureAlexander E. Kostyunin0Tatiana V. Glushkova1Arseniy A. Lobov2Evgeny A. Ovcharenko3Bozhana R. Zainullina4Leo A. Bogdanov5Daria K. Shishkova6Victoria E. Markova7Maksim A. Asanov8Rinat A. Mukhamadiyarov9Elena A. Velikanova10Tatiana N. Akentyeva11Maria A. Rezvova12Alexander N. Stasev13Alexey V. Evtushenko14Leonid S. Barbarash15Anton G. Kutikhin16Department of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationDepartment of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationDepartment of Regenerative Biomedicine Research Institute of Cytology St. Petersburg Russian FederationDepartment of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationCentre for Molecular and Cell Technologies St. Petersburg State University Research Park St. Petersburg State University, Universitetskaya Embankment St. Petersburg Russian FederationDepartment of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationDepartment of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationDepartment of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationDepartment of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationDepartment of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationDepartment of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationDepartment of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationDepartment of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationDepartment of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationDepartment of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationDepartment of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationDepartment of Experimental Medicine Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo Russian FederationBackground Whereas the risk factors for structural valve degeneration (SVD) of glutaraldehyde‐treated bioprosthetic heart valves (BHVs) are well studied, those responsible for the failure of BHVs fixed with alternative next‐generation chemicals remain largely unknown. This study aimed to investigate the reasons behind the development of SVD in ethylene glycol diglycidyl ether–treated BHVs. Methods and Results Ten ethylene glycol diglycidyl ether–treated 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‐degrading enzymes and their tissue inhibitors, lipid deposition, and calcification. In contrast with dysfunctional AVs, failing BHVs suffered from complement‐driven 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‐derived MMP‐8 and plasma‐derived MMP‐9), 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‐9 was mostly expressed in the disorganized prosthetic extracellular matrix, suggesting plasma‐derived proteases as the primary culprit of SVD in ethylene glycol diglycidyl ether–treated BHVs. Hence, hemodynamic stress and progressive accumulation of proteases led to the extracellular matrix degeneration and dystrophic calcification, ultimately resulting in SVD. Conclusions Neutrophil‐ and plasma‐derived proteases are responsible for the loss of BHV mechanical competence and need to be thwarted to prevent SVD.https://www.ahajournals.org/doi/10.1161/JAHA.122.028215bacterial invasionbioprosthetic heart valvesmatrix metalloproteinasesneutrophil infiltrationstructural valve degeneration |
| spellingShingle | Alexander E. Kostyunin Tatiana V. Glushkova Arseniy A. Lobov Evgeny A. Ovcharenko Bozhana R. Zainullina Leo A. Bogdanov Daria K. Shishkova Victoria E. Markova Maksim A. Asanov Rinat A. Mukhamadiyarov Elena A. Velikanova Tatiana N. Akentyeva Maria A. Rezvova Alexander N. Stasev Alexey V. Evtushenko Leonid S. Barbarash Anton G. Kutikhin Proteolytic Degradation Is a Major Contributor to Bioprosthetic Heart Valve Failure Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease bacterial invasion bioprosthetic heart valves matrix metalloproteinases neutrophil infiltration structural valve degeneration |
| title | Proteolytic Degradation Is a Major Contributor to Bioprosthetic Heart Valve Failure |
| title_full | Proteolytic Degradation Is a Major Contributor to Bioprosthetic Heart Valve Failure |
| title_fullStr | Proteolytic Degradation Is a Major Contributor to Bioprosthetic Heart Valve Failure |
| title_full_unstemmed | Proteolytic Degradation Is a Major Contributor to Bioprosthetic Heart Valve Failure |
| title_short | Proteolytic Degradation Is a Major Contributor to Bioprosthetic Heart Valve Failure |
| title_sort | proteolytic degradation is a major contributor to bioprosthetic heart valve failure |
| topic | bacterial invasion bioprosthetic heart valves matrix metalloproteinases neutrophil infiltration structural valve degeneration |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.122.028215 |
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