Identification of tissue factor in experimental aortic valve sclerosis.
BACKGROUND
Aortic valve sclerosis (AVS) shares epidemiological and histological similarities with atherosclerosis. Tissue factor (TF), the main initiator of blood coagulation, is present in atherosclerotic plaques and contributes to their thrombogenicity. We aimed to analyze valvular TF expression in addition to other components of atherosclerosis in two models of AVS.


METHODS
Forty-five rabbits were randomly assigned to receive either normal chow (Ctrl, n=15), or 1% cholesterol-enriched chow alone (Hyperchol, n=15) or associated with vitamin D(2) (VitD, n=15), for 12 weeks. Aortic valve (AV) performance, leaflet structure, cellular and lipid infiltration, and TF expression were assessed using Doppler, histology, and immunohistochemistry, respectively, and TF activity was evaluated in AV leaflets.


RESULTS
Hyperchol and VitD animals developed abnormal leaflet thickening, with a significant alteration of AV performance in VitD animals. Leaflet thickening was related to the development of fatty plaque neolesions on the aortic side of the leaflets, displaying extracellular matrix disorganization, lipid and cellular infiltration, and calcification in VitD animals. TF was found on the leaflet aortic side in Ctrl animals and was identified in AVS lesions in both Hyperchol and VitD animals. TF immunostaining area and valvular activity increased significantly across the three groups.


CONCLUSIONS
Experimental AVS lesions that are present on the aortic side of leaflets display numerous characteristics of vascular atherosclerosis, including TF expression. Identification of TF associated with other components of the atherosclerotic process in AVS lesions strengthens the link between atherosclerosis and AVS.
Marechaux
Sylvestre
S
INSERM ERI, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille II, France.
Corseaux
Delphine
D
Vincentelli
Andre
A
Richardson
Marjorie
M
Ung
Alexandre
A
Susen
Sophie
S
Zawadzki
Christophe
C
Beregi
Jean-Paul
JP
Ezekowitz
Michael D
MD
Jude
Brigitte
B
Le Tourneau
Thierry
T
D000818:Animals; D001021:Aortic Valve / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001024:Aortic Valve Stenosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D004872:Ergocalciferols / Q000008:administration & dosage; D006439:Hemodynamics; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D011817:Rabbits; D012598:Sclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D013925:Thromboplastin / Q000378:metabolism*
D002791:Cholesterol, Dietary; D004872:Ergocalciferols; D013925:Thromboplastin