Bioprosthetic Valve Deterioration: Accumulation of Circulating Proteins and Macrophages in the Valve Interstitium.

Histologic evaluations revealed excessive accumulations of macrophages and absence of fibroblastic interstitial cells in explanted bioprosthetic valves. Comprehensive gene and protein expression analysis and histology unveiled an accumulation of fibrinogen and plasminogen, an activator of infiltrated macrophages, from degenerated valve surfaces in the interstitial spaces. These pathologies were completely reproduced in a goat model replaced with an autologous pericardium-derived aortic valve. Further preclinical animal experiments using goats demonstrated that preventing infiltration of macrophages and circulating proteins by increasing collagen density and leaflet strength is an effective treatment option.
Competing Interests: This work was supported by Grants-in-Aid for Scientific Research (18K16396 to Dr Namiguchi, 16K10631, and 19H03740 to Dr Izutani, 19K17603 to Dr Hamaguchi, and 19K08585 and 16K109503 to Dr Aono) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; the Takeda Science Foundation (grants 2016 and 2020 to Dr Sakaue); the Public Trust Cardiovascular Research Foundation (grant 2017 to Dr Sakaue); the SENSHIN Medical Research Foundation (grant 2016 to Drs Aono and 2020 to Dr Sakaue); and the MSD Life Science Foundation, Public Interest Incorporated Foundation (grant 2016 to Dr Aono). Dr Nakayama is an employee of Biotube. There are no financial relationships between Dr Nakayama and the other coauthors, and experimental materials and funding used in this study were not provided by industry. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(© 2023 The Authors.)