PhD Scientific Days 2023

Molecular Sciences - Posters L

Nanoscale structural comparison of fibrillin-1 microfibrils isolated from Marfan and non-Marfan syndrome human aorta

Text of the abstract

Introduction: Fibrillin-1 microfibrils are essential elements of the extracellular matrix serving as a scaffold for the deposition of elastin and endowing connective tissues with tensile strength and elasticity. Mutations in the fibrillin-1 gene (FBN1) are linked to Marfan syndrome (MFS), a systemic connective tissue disorder that, besides other heterogeneous symptoms, usually manifests in life-threatening aortic complications. The aortic involvement may be explained by a dysregulation of microfibrillar function and, conceivably, alterations in the microfibrils’ supramolecular structure.
Aims: To perform a nanoscale structural characterization of fibrillin-1 microfibrils isolated from human aortic samples with different FBN1 gene mutations and to compare them with microfibrillar assemblies purified from non-MFS human aortic samples.
Methods: Aortic wall samples were obtained from patients undergoing specific cardiovascular surgical interventions. Fibrillin-rich microfibrils were extracted by bacterial collagenase digestion and purified by size-exclusion chromatography. Atomic force microscopy was employed to visualize and study the microfibrillar assemblies.
Results: Fibrillin-1 microfibrils displayed a characteristic “beads-on-a-string” appearance. The microfibrillar assemblies were investigated for bead geometry (height, length, and width), interbead region height, and periodicity. MFS fibrillin-1 microfibrils had a slightly higher mean bead height, but the bead length and width, as well as the interbead height, were significantly smaller in the MFS group. The mean periodicity varied around 50–52 nm among samples.
Conclusion: The data suggest an overall thinner and presumably more frail structure for the MFS fibrillin-1 microfibrils, which may play a role in the development of MFS-related aortic symptomatology.
Funding: This research was supported by grants from the Hungarian National Research, Development and Innovation Office (K135360 to M.S.Z.K. and project TKP2021-EGA-23) and the New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund (ÚNKP-22-3-I-SE-49 to C.M.Ș.). Project no. RRF-2.3.1-21-2022-00003 (National Cardiovascular Laboratory) has been implemented with the support provided by the European Union.