Medin and transthyretin: a new amyloid double act in the aortic wall and valves.

Background: Cross-seeding and co-assembly of multiple amyloid species are increasingly recognised in various organs and amyloidoses. Medin and wild-type transthyretin (TTR) both form age-related amyloid deposits and have been identified within the aortic wall. Given the emerging role of amyloid in aortic disease, this study investigates the potential colocalisation of TTR and medin in the aorta.

Methods: Medin and TTR levels were measured in thoracic aortic wall samples from 30 patients undergoing surgical replacement for aortic aneurysm. Immunohistochemistry was performed on five aortic wall samples and two excised aortic valves to assess colocalisation patterns. In vitro assays, including Thioflavin T fluorescence and immunogold labelling electron microscopy, evaluated protein co-aggregation and fibril formation. Cellular toxicity assays examined the impact of TTR on medin aggregates.

Results: A positive correlation was observed between medin and TTR levels in the aortic wall. In vitro assays revealed enhanced fibril formation and co-aggregation, with TTR reducing the cellular toxicity of medin aggregates, suggesting altered fibril properties. Immunohistochemistry confirmed colocalisation of medin and TTR in both aortic wall and valve samples.

Conclusions: This study identifies a novel association between medin and TTR, highlighting a potential role for co-aggregation in vascular amyloid deposition.