Amyloid substance within stenotic aortic valves promotes mineralization.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Laboratoire d'Études Moléculaires des Valvulopathies (LEMV), Groupe de Recherche en Valvulopathies (GRV), Quebec Heart and Lung Institute/Research Center, Department of Surgery, Québec City, QC, CanadaQuebec Heart and Lung Institute/Research Center, Québec City, QC, Canada, andDepartment of Social and Preventive Medicine, Division of Kinesiology, Laval University, Québec City, QC, Canada.
Audrey
A
Audet
Nancy
N
Côté
Christian
C
Couture
Yohan
Y
Bossé
Jean-Pierre
JP
Després
Philippe
P
Pibarot
Patrick
P
Mathieu
D000368:Aged; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D001021:Aortic Valve / Q000378:metabolism / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000378:metabolism* / Q000473:pathology*; D016632:Apolipoprotein A-I / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D002114:Calcinosis / Q000378:metabolism* / Q000473:pathology*; D003224:Congo Red; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D013194:Staining and Labeling
D000682:Amyloid; D016632:Apolipoprotein A-I; D008074:Lipoproteins; D003224:Congo Red