Altered Expression of ADAMs ( A D isintegrin A nd M etalloproteinase) in Fibrillating Human Atria

Abstract

Background — ADAMs ( A D isintegrin A nd M etalloproteinase) are ectoproteases that have recently been reported to be expressed in cardiac tissue. Although they are known to regulate cell-cell and cell-matrix interactions, their pathophysiological role in various cardiac diseases is unclear. The purpose of the present study was to determine whether structural remodeling of the atria during atrial fibrillation (AF) is associated with altered ADAM expression. Methods and Results — Atrial tissue samples of 30 patients undergoing open-heart surgery were examined. Fifteen patients had persistent AF (≥6 months), and the remaining 15 patients had no history of AF. ADAM9, ADAM10, and ADAM15 expression was analyzed quantitatively at the mRNA and protein levels. ADAM expression was localized by immunohistochemistry. ADAM expression was correlated with amounts of integrins β 1 and β 3 . The amount of ADAM10 protein more than doubled during AF (82±15 versus 36±8 U; P <0.01). Amounts of ADAM15 protein (102±12 versus 40±6 U; P <0.01) and mRNA (24.0±5.6 versus 10.5±2.5 U; P <0.05) increased significantly during AF compared with sinus rhythm. ADAM9 protein was not detected in any sample. ADAM/integrin ratios showed an increase of 4- to 6-fold ( P <0.05) in patients with AF who had significantly dilated atria (4.94±0.6 versus 4.3±0.7 cm; P <0.05). ADAM/integrin ratios correlated with atrial diameter. Conclusions — AF is associated with an increase in the expression of ADAM10 and ADAM15. Enhanced ADAM-dependent disintegrin and metalloproteinase activity may be a molecular mechanism that contributes to the dilation of fibrillating human atria.