Biochemical and histological evidence of deteriorated bioprosthetic valve leaflets: the accumulation of fibrinogen and plasminogen

Tomohisa Sakaue, Hirotomo Nakaoka, Fumiaki Shikata, Jun Aono, Mie Kurata, Teruyoshi Uetani, Mika Hamaguchi, Ai Kojima, Shunji Uchita, Takumi Yasugi, Haruhiko Higashi, Jun Suzuki (+4 others)
2018 Biology Open  
Calcification of bioprosthetic valves (BVs) implanted in aortic position can result in gradual deterioration and necessitate aortic valve replacement. The molecular mechanism of calcium deposition on BV leaflets has been investigated, but remains to be fully elucidated. The present study aimed to identify explanted bioprosthetic valve (eBV)specific proteins using a proteomics approach and to unveil their biochemical and histological involvements in calcium deposition on BV leaflets.
more » ... aflets. Calcification, fibrosis, and glycosylation of the valves were histologically assessed using Von Kossa, Masson's Trichrome and Alcian Blue staining, as well as immunostaining. Protein expression in the explanted biological valves was analysed using proteomics and western blotting. In a histological evaluation, αSMApositive myofibroblasts were not observed in eBV, whereas severe fibrosis occurred around calcified areas. SDS-PAGE revealed three major bands with considerably increased intensity in BV leaflets that were identified as plasminogen and fibrinogen gamma chain (100 kDa), and fibrinogen beta chain (50 and 37 kDa) by mass analysis. Immunohistochemistry showed that fibrinogen β-chain was distributed throughout the valve tissue. On the contrary, plasminogen was strongly stained in CD68-positive macrophages, as evidenced by immunofluorescence. The results suggest that two important blood coagulation-related proteins, plasminogen and fibrinogen, might affect the progression of BV degeneration.
doi:10.1242/bio.034009 pmid:30089611 fatcat:xq7hvaqdpradzjfu2z6fvzmgtq