title: Increased endothelial cell expression of alpha3beta1 integrin in cardiac valvulopathy in the primary (Hughes) and secondary antiphospholipid syndrome.
abstract: The objective of this work was to determine markers of endothelial cell activation in valves from patients with antiphospholipid syndrome (APS) and heart valve involvement, in order to establish a role for endothelial cells in the pathogenesis of the valvular disease. Sixteen valves from ten patients with APS, obtained from autopsies or removed during valve replacement, were studied. Two groups of valves were used as controls. One group included seven normal valves from patients who died from non-cardiac diseases. The other group of valves were obtained from patients with bacterial endocarditis during autopsies or valve replacement operations. Immunoperoxidase and immunofluorescence stainings with antibodies to human immunoglobulins, endothelial cells, alpha3beta1 integrin, collagen IV, laminin and fibronectin were employed. Three histopathological patterns were apparent: normal valves, valves with verrucous endocarditis and valves with fibrocalcific changes. In all the valves with verrucous endocarditis the following findings were observed: (1) increased expression of the alpha3beta1 integrin on the endothelial cells, (2) increased amount of collagen IV, laminin and fibronectin, (3) proliferation of blood vessels and (4) linear subendothelial deposition of immunoglobulins and complement. The valves with fibrocalcific changes were deformed and showed a thick layer of collagen IV, laminin and fibronectin, yet in two valves the indothelial cells showed an expression of the alpha3beta1 integrin. The control valves did not express the integrin and had only a thin subendothelial band of collagen IV. In valves from patients with APS, 1 markers of endothelial cell activation are upregulated while the inflammatory exudate is scant. There is also a prominent deposition of immunoglobulins in the valves from patients with APS, suggesting a possible association between the deposition of the antibodies and the activation of the endothelial cells in APS.
authors.affiliation: Institute of Pathology, Department of Medicine 'B', Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Afek
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
authors.forename: R
authors.initials: R
authors.lastname: Manor
authors.forename: I
authors.initials: I
authors.lastname: Goldberg
authors.forename: L
authors.initials: L
authors.lastname: Ziporen
authors.forename: J
authors.initials: J
authors.lastname: George
authors.forename: S
authors.initials: S
authors.lastname: Polak-Charcon
authors.forename: M C
authors.initials: MC
authors.lastname: Amigo
authors.forename: R
authors.initials: R
authors.lastname: Garcia-Torres
authors.forename: R
authors.initials: R
authors.lastname: Segal
authors.forename: J
authors.initials: J
authors.lastname: Kopolovic
mesh_terms: D000199:Actins / Q000032:analysis / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D017153:Antibodies, Anticardiolipin / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis / Q000096:biosynthesis; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000378:metabolism*; D001485:Basement Membrane / Q000276:immunology / Q000378:metabolism; D003094:Collagen / Q000032:analysis / Q000096:biosynthesis; D004697:Endocarditis, Bacterial / Q000276:immunology / Q000378:metabolism*; D004727:Endothelium / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D005122:Exudates and Transudates; D005260:Female; D005353:Fibronectins / Q000032:analysis / Q000096:biosynthesis; D006349:Heart Valve Diseases / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D039201:Integrin alpha3beta1; D016023:Integrins / Q000032:analysis / Q000096:biosynthesis*; D007797:Laminin / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D017474:Receptors, Laminin / Q000032:analysis / Q000096:biosynthesis; D000097382:CD68 Molecule
chemical_list: D000199:Actins; D017153:Antibodies, Anticardiolipin; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003094:Collagen; D005353:Fibronectins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D039201:Integrin alpha3beta1; D016023:Integrins; D007797:Laminin; D017474:Receptors, Laminin; C067980:CD68 antigen, human; D000097382:CD68 Molecule