Exploring thoracic aorta ECM alterations in Marfan syndrome: insights into aorta wall structure
Abstract Marfan syndrome is a connective tissue disorder caused by FBN1 mutations, leading to aortic wall fragility and increased susceptibility to aneurysm and dissection. This study investigated microstructural and molecular alterations in the thoracic aorta of Fbn1mgΔlpn mice, with a focus on the...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-09665-w |
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| author | Rodrigo Barbosa de Souza Luara Lucena Cassiano Philipp Barnowski Sara Ventura Walter Miguel Turato Suelen Cristina Russafa Nascimento Giovanna Lodi Mignanelli Waldir Caldeira Ana Maria Cristina Rebelo Pinto da Fonseca Martins Flavio de Carvalho Luposeli Francisco Rafael Martins Laurindo Dieter P. Reinhardt Gerhard Sengle Ivan Hong Jun Koh Keith M. Meek Philip N. Lewis |
| author_facet | Rodrigo Barbosa de Souza Luara Lucena Cassiano Philipp Barnowski Sara Ventura Walter Miguel Turato Suelen Cristina Russafa Nascimento Giovanna Lodi Mignanelli Waldir Caldeira Ana Maria Cristina Rebelo Pinto da Fonseca Martins Flavio de Carvalho Luposeli Francisco Rafael Martins Laurindo Dieter P. Reinhardt Gerhard Sengle Ivan Hong Jun Koh Keith M. Meek Philip N. Lewis |
| author_sort | Rodrigo Barbosa de Souza |
| collection | DOAJ |
| description | Abstract Marfan syndrome is a connective tissue disorder caused by FBN1 mutations, leading to aortic wall fragility and increased susceptibility to aneurysm and dissection. This study investigated microstructural and molecular alterations in the thoracic aorta of Fbn1mgΔlpn mice, with a focus on the tunica intima and media. Histological and ultrastructural analyses demonstrated elastic fiber fragmentation and reduced fibrillin-1 expression. In the intima, endothelial cells showed partial detachment and decreased levels of fibrillin-1, perlecan, collagen IV, and α5β1 integrins, suggesting compromised adhesion to the extracellular matrix. Serial block-face scanning electron microscopy revealed discontinuities in the internal elastic lamina. In the media, we observed reduced fibronectin, altered α5β1 integrin distribution, and increased α-smooth muscle actin, indicative of remodeling in elastin–contractile units. Second harmonic generation imaging revealed increased collagen deposition, and thickness in areas of elastic fiber disruption, along with reduced and disorganized type III collagen and increased type I collagen. Echocardiographic evaluation showed aortic root, and ascendant-aorta dilatation, altered blood flow, and diastolic dysfunction. Elastic fiber integrity correlated strongly with fibrillin-1 expression (r = 0.93, p = 0.0003) and aortic blood flow (r = 0.77, p = 0.0064). These results suggest that early alterations in matrix organization and endothelial–matrix interactions may contribute to aortic wall weakening in Fbn1mgΔlpn mice. |
| format | Article |
| id | doaj-art-789daa28b5074671a6ca48e5e292de4e |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-789daa28b5074671a6ca48e5e292de4e2025-08-20T03:43:15ZengNature PortfolioScientific Reports2045-23222025-07-0115111810.1038/s41598-025-09665-wExploring thoracic aorta ECM alterations in Marfan syndrome: insights into aorta wall structureRodrigo Barbosa de Souza0Luara Lucena Cassiano1Philipp Barnowski2Sara Ventura3Walter Miguel Turato4Suelen Cristina Russafa Nascimento5Giovanna Lodi Mignanelli6Waldir Caldeira7Ana Maria Cristina Rebelo Pinto da Fonseca Martins8Flavio de Carvalho Luposeli9Francisco Rafael Martins Laurindo10Dieter P. Reinhardt11Gerhard Sengle12Ivan Hong Jun Koh13Keith M. Meek14Philip N. Lewis15Department of Descriptive and Topographic Anatomy, Faculty of Santa MarcelinaAquaculture Research and Development Center (CPDA), Fishing Institute of São PauloDepartment of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of CologneVascular Biology Laboratory, The Heart Institute, University of Sao Paulo School of MedicineDepartment of Clinical and Toxicological Analysis, University of São PauloLaboratory of Genetics and Molecular Cardiology, The Heart Institute, University of Sao Paulo School of MedicineDepartment of Descriptive and Topographic Anatomy, Faculty of Santa MarcelinaDepartment of Genetics and Evolutionary Biology, University of São PauloDepartment of Animal Sanity, Biologic Institute of São PauloDepartment of Surgery, Federal University of São PauloVascular Biology Laboratory, The Heart Institute, University of Sao Paulo School of MedicineFaculty of Medicine and Health Sciences, McGill UniversityDepartment of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of CologneDepartment of Clinical and Toxicological Analysis, University of São PauloStructural Biophysics Research Group, School of Optometry and Vision Sciences, Cardiff UniversityStructural Biophysics Research Group, School of Optometry and Vision Sciences, Cardiff UniversityAbstract Marfan syndrome is a connective tissue disorder caused by FBN1 mutations, leading to aortic wall fragility and increased susceptibility to aneurysm and dissection. This study investigated microstructural and molecular alterations in the thoracic aorta of Fbn1mgΔlpn mice, with a focus on the tunica intima and media. Histological and ultrastructural analyses demonstrated elastic fiber fragmentation and reduced fibrillin-1 expression. In the intima, endothelial cells showed partial detachment and decreased levels of fibrillin-1, perlecan, collagen IV, and α5β1 integrins, suggesting compromised adhesion to the extracellular matrix. Serial block-face scanning electron microscopy revealed discontinuities in the internal elastic lamina. In the media, we observed reduced fibronectin, altered α5β1 integrin distribution, and increased α-smooth muscle actin, indicative of remodeling in elastin–contractile units. Second harmonic generation imaging revealed increased collagen deposition, and thickness in areas of elastic fiber disruption, along with reduced and disorganized type III collagen and increased type I collagen. Echocardiographic evaluation showed aortic root, and ascendant-aorta dilatation, altered blood flow, and diastolic dysfunction. Elastic fiber integrity correlated strongly with fibrillin-1 expression (r = 0.93, p = 0.0003) and aortic blood flow (r = 0.77, p = 0.0064). These results suggest that early alterations in matrix organization and endothelial–matrix interactions may contribute to aortic wall weakening in Fbn1mgΔlpn mice.https://doi.org/10.1038/s41598-025-09665-wMarfan syndromeAortaExtracellular matrixFibrillin-1AneurysmCollagen |
| spellingShingle | Rodrigo Barbosa de Souza Luara Lucena Cassiano Philipp Barnowski Sara Ventura Walter Miguel Turato Suelen Cristina Russafa Nascimento Giovanna Lodi Mignanelli Waldir Caldeira Ana Maria Cristina Rebelo Pinto da Fonseca Martins Flavio de Carvalho Luposeli Francisco Rafael Martins Laurindo Dieter P. Reinhardt Gerhard Sengle Ivan Hong Jun Koh Keith M. Meek Philip N. Lewis Exploring thoracic aorta ECM alterations in Marfan syndrome: insights into aorta wall structure Scientific Reports Marfan syndrome Aorta Extracellular matrix Fibrillin-1 Aneurysm Collagen |
| title | Exploring thoracic aorta ECM alterations in Marfan syndrome: insights into aorta wall structure |
| title_full | Exploring thoracic aorta ECM alterations in Marfan syndrome: insights into aorta wall structure |
| title_fullStr | Exploring thoracic aorta ECM alterations in Marfan syndrome: insights into aorta wall structure |
| title_full_unstemmed | Exploring thoracic aorta ECM alterations in Marfan syndrome: insights into aorta wall structure |
| title_short | Exploring thoracic aorta ECM alterations in Marfan syndrome: insights into aorta wall structure |
| title_sort | exploring thoracic aorta ecm alterations in marfan syndrome insights into aorta wall structure |
| topic | Marfan syndrome Aorta Extracellular matrix Fibrillin-1 Aneurysm Collagen |
| url | https://doi.org/10.1038/s41598-025-09665-w |
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