Amyloid substance within stenotic aortic valves promotes mineralization

Authors: Audet, AudreyCôté, NancyCouture, ChristianBossé, YohanDesprés, Jean-PierrePibarot, PhilippeMathieu, Patrick
Abstract: AIMS: Accumulation of apolipoproteins may play an important role in the pathobiology of calcific aortic valve disease (CAVD). We aimed to explore the hypothesis that apolipoprotein-derived amyloid could play a role in the development of CAVD. METHODS AND RESULTS: In 70 explanted CAVD valves and 15 control non-calcified aortic valves, we assessed the presence of amyloid by using Congo red staining. Immunohistochemistry was performed to document the presence of apolipoprotein AI (Apo-AI). Apoptosis was documented by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) studies performed in control and CAVD valves. Control valves were free of amyloid. Deposition of amyloid was detected in all CAVD valves, and the amount was positively correlated with plasma high-density lipoprotein and Apo-AI levels. Apo-AI within CAVD valves co-localized with intense staining of fibrillar amyloid. In turn, deposition of amyloid co-localized with apoptosis near mineralized areas. Isolation of amyloid fibrils confirmed that Apo-AI is a major component of amyloid deposits in CAVD. In vitro, CAVD-derived amyloid extracts increased apoptosis and mineralization of isolated aortic valvular interstitial cells. CONCLUSION: Apo-AI is a major component of amyloid substance present within CAVD valves. Furthermore, amyloid deposits participate in mineralization in CAVD by promoting apoptosis of valvular interstitial cells.
Document Type: Article de recherche
Issue Date: 1 October 2012
Open Access Date: Restricted access
Document version: VoR
Permalink: http://hdl.handle.net/20.500.11794/7868
This document was published in: Histopathology, Vol. 61 (4), 610-619 (2012)
http://dx.doi.org/10.1111/j.1365-2559.2012.04265.x
Blackwell Scientific
Alternative version: 10.1111/j.1365-2559.2012.04265.x
http://www.ncbi.nlm.nih.gov/pubmed/22642224
Collection:Articles publiés dans des revues avec comité de lecture

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