Transcriptomic profiling of calcified aortic valves in clonal hematopoiesis of indeterminate potential carriers
Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the presence of clones of mutated blood cells without overt blood diseases. In the last few years, it has emerged that CHIP is associated with atherosclerosis and coronary calcification and that it is an independent...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-24130-8 |
| _version_ | 1811190396600975360 |
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| author | Francesco Vieceli Dalla Sega Domenico Palumbo Francesca Fortini Ylenia D’Agostino Paolo Cimaglia Luisa Marracino Paolo Severi Oriana Strianese Roberta Tarallo Giovanni Nassa Giorgio Giurato Giovanni Pecoraro Serena Caglioni Elisa Mikus Alberto Albertini Gianluca Campo Roberto Ferrari Paola Rizzo Alessandro Weisz Francesca Rizzo |
| author_facet | Francesco Vieceli Dalla Sega Domenico Palumbo Francesca Fortini Ylenia D’Agostino Paolo Cimaglia Luisa Marracino Paolo Severi Oriana Strianese Roberta Tarallo Giovanni Nassa Giorgio Giurato Giovanni Pecoraro Serena Caglioni Elisa Mikus Alberto Albertini Gianluca Campo Roberto Ferrari Paola Rizzo Alessandro Weisz Francesca Rizzo |
| author_sort | Francesco Vieceli Dalla Sega |
| collection | DOAJ |
| description | Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the presence of clones of mutated blood cells without overt blood diseases. In the last few years, it has emerged that CHIP is associated with atherosclerosis and coronary calcification and that it is an independent determinant of cardiovascular mortality. Recently, CHIP has been found to occur frequently in patients with calcific aortic valve disease (CAVD) and it is associated with a poor prognosis after valve replacement. We assessed the frequency of CHIP by DNA sequencing in the blood cells of 168 CAVD patients undergoing surgical aortic valve replacement or transcatheter aortic valve implantation and investigated the effect of CHIP on 12 months survival. To investigate the pathological process of CAVD in CHIP carriers, we compared by RNA-Seq the aortic valve transcriptome of patients with or without CHIP and non-calcific controls. Transcriptomics data were validated by immunohistochemistry on formalin-embedded aortic valve samples. We confirm that CHIP is common in CAVD patients and that its presence is associated with higher mortality following valve replacement. Additionally, we show, for the first time, that CHIP is often accompanied by a broad cellular and humoral immune response in the explanted aortic valve. Our results suggest that an excessive inflammatory response in CHIP patients may be related to the onset and/or progression of CAVD and point to B cells as possible new effectors of CHIP-induced inflammation. |
| first_indexed | 2024-04-11T14:50:42Z |
| format | Article |
| id | doaj.art-722cfcecf3b54ee19ad268ce2c3f8664 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T14:50:42Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-722cfcecf3b54ee19ad268ce2c3f86642022-12-22T04:17:28ZengNature PortfolioScientific Reports2045-23222022-11-0112111710.1038/s41598-022-24130-8Transcriptomic profiling of calcified aortic valves in clonal hematopoiesis of indeterminate potential carriersFrancesco Vieceli Dalla Sega0Domenico Palumbo1Francesca Fortini2Ylenia D’Agostino3Paolo Cimaglia4Luisa Marracino5Paolo Severi6Oriana Strianese7Roberta Tarallo8Giovanni Nassa9Giorgio Giurato10Giovanni Pecoraro11Serena Caglioni12Elisa Mikus13Alberto Albertini14Gianluca Campo15Roberto Ferrari16Paola Rizzo17Alessandro Weisz18Francesca Rizzo19Maria Cecilia Hospital, GVM Care and ResearchDepartment of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of SalernoMaria Cecilia Hospital, GVM Care and ResearchDepartment of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of SalernoMaria Cecilia Hospital, GVM Care and ResearchDepartment of Translational Medicine, Laboratory for Technologies of Advanced Therapies (LTTA), University of FerraraDepartment of Translational Medicine, Laboratory for Technologies of Advanced Therapies (LTTA), University of FerraraClinical Research and Innovation, Clinica Montevergine S.P.A.Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of SalernoDepartment of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of SalernoDepartment of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of SalernoDepartment of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of SalernoCardiology Unit, Azienda Ospedaliero-Universitaria di Ferrara, University of FerraraMaria Cecilia Hospital, GVM Care and ResearchMaria Cecilia Hospital, GVM Care and ResearchCardiology Unit, Azienda Ospedaliero-Universitaria di Ferrara, University of FerraraMaria Cecilia Hospital, GVM Care and ResearchMaria Cecilia Hospital, GVM Care and ResearchDepartment of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of SalernoDepartment of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of SalernoAbstract Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the presence of clones of mutated blood cells without overt blood diseases. In the last few years, it has emerged that CHIP is associated with atherosclerosis and coronary calcification and that it is an independent determinant of cardiovascular mortality. Recently, CHIP has been found to occur frequently in patients with calcific aortic valve disease (CAVD) and it is associated with a poor prognosis after valve replacement. We assessed the frequency of CHIP by DNA sequencing in the blood cells of 168 CAVD patients undergoing surgical aortic valve replacement or transcatheter aortic valve implantation and investigated the effect of CHIP on 12 months survival. To investigate the pathological process of CAVD in CHIP carriers, we compared by RNA-Seq the aortic valve transcriptome of patients with or without CHIP and non-calcific controls. Transcriptomics data were validated by immunohistochemistry on formalin-embedded aortic valve samples. We confirm that CHIP is common in CAVD patients and that its presence is associated with higher mortality following valve replacement. Additionally, we show, for the first time, that CHIP is often accompanied by a broad cellular and humoral immune response in the explanted aortic valve. Our results suggest that an excessive inflammatory response in CHIP patients may be related to the onset and/or progression of CAVD and point to B cells as possible new effectors of CHIP-induced inflammation.https://doi.org/10.1038/s41598-022-24130-8 |
| spellingShingle | Francesco Vieceli Dalla Sega Domenico Palumbo Francesca Fortini Ylenia D’Agostino Paolo Cimaglia Luisa Marracino Paolo Severi Oriana Strianese Roberta Tarallo Giovanni Nassa Giorgio Giurato Giovanni Pecoraro Serena Caglioni Elisa Mikus Alberto Albertini Gianluca Campo Roberto Ferrari Paola Rizzo Alessandro Weisz Francesca Rizzo Transcriptomic profiling of calcified aortic valves in clonal hematopoiesis of indeterminate potential carriers Scientific Reports |
| title | Transcriptomic profiling of calcified aortic valves in clonal hematopoiesis of indeterminate potential carriers |
| title_full | Transcriptomic profiling of calcified aortic valves in clonal hematopoiesis of indeterminate potential carriers |
| title_fullStr | Transcriptomic profiling of calcified aortic valves in clonal hematopoiesis of indeterminate potential carriers |
| title_full_unstemmed | Transcriptomic profiling of calcified aortic valves in clonal hematopoiesis of indeterminate potential carriers |
| title_short | Transcriptomic profiling of calcified aortic valves in clonal hematopoiesis of indeterminate potential carriers |
| title_sort | transcriptomic profiling of calcified aortic valves in clonal hematopoiesis of indeterminate potential carriers |
| url | https://doi.org/10.1038/s41598-022-24130-8 |
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