Exploring thoracic aorta ECM alterations in Marfan syndrome: insights into aorta wall structure

de Souza, Rodrigo Barbosa, Cassiano, Luara Lucena, Barnowski, Philipp, Ventura, Sara, Turato, Walter Miguel, Nascimento, Suelen Cristina Russafa, Mignanelli, Giovanna Lodi, Caldeira, Waldir, da Fonseca Martins, Ana Maria Cristina Rebelo Pinto, de Carvalho Luposeli, Flavio, Laurindo, Francisco Rafael Martins, Reinhardt, Dieter P., Sengle, Gerhard, Koh, Ivan Hong Jun, Meek, Keith M. ORCID: https://orcid.org/0000-0002-9948-7538 and Lewis, Philip N. ORCID: https://orcid.org/0000-0002-3353-0708 2025. Exploring thoracic aorta ECM alterations in Marfan syndrome: insights into aorta wall structure. Scientific Reports 15 (1) , 26665. 10.1038/s41598-025-09665-w

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Schools > Optometry and Vision Sciences
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Nature Research
Date of First Compliant Deposit:	31 July 2025
Date of Acceptance:	30 June 2025
Last Modified:	31 Jul 2025 09:00
URI:	https://orca.cardiff.ac.uk/id/eprint/180174

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