Increased endothelial cell expression of alpha(3)beta(1) integrin in cardiac valvulopathy in the primary (Hughes) and secondary antiphospholipid syndrome

The objective of this work was to determine markers of endothelial cell act ivation in valves from patients with antiphospholipid syndrome (APS) and he art valve involvement, in order to establish a role for endothelial cells i n the pathogenesis of the valvular disease. Sixteen valves from ten patients with APS, obtained from autopsies or remov ed during valve replacement, were studied. Two groups of valves were used a s controls. One group included seven normal valves from patients who died f rom non-cardiac diseases. The other group of valves were obtained from pati ents with bacterial endocarditis during autopsies or valve replacement oper ations. Immunoperoxidase and immunofluorescence stainings with antibodies t o human immunoglobulins, endothelial cells, alpha(3)beta(1) integrin, colla gen 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 va lves with verrucous endocarditis the following findings were observed. (1) increased expression of the alpha(3)beta(1) integrin on the endothelial cel ls, (2) increased amount of collagen IV, laminin and fibronectin, (3) proli feration of blood vessels and (4) linear subendothelial deposition of immun oglobulins and complement. The valves with fibrocalcific changes were defor med and showed a thick layer of collagen IV, laminin and fibronectin, yet i n two valves the indothelial cells showed an expression of the alpha(2)beta (1) 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,' markers of endothelial cell activation a re upregulated while the inflammatory exudate is scant. There is also a pro minent 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.