Accumulation of oxidized LDL in human semilunar valves correlates with coronary atherosclerosis

Objective: Recent data indicate that oxidized low-density lipoprotein (ox-LDL) has several proatherogenic effects, e.g. induction of macrophage chemoattractants, adhesion molecules, cytokines, type-1 plasminogen activator inhibitor and platelet-derived growth factor A-chain by smooth muscle cells. Therefore, ox-LDL has been utilized as a marker of oxidative modification of proteins in atherosclerosis. Because heart valves consist of smooth muscle cells, fibroblasts and endothelial cells, and because valvular disease and coronary atherosclerosis could result from similar biological processes, we investigated ox-LDL accumulation in isolated aortic and pulmonary valves and coronary arteries from patients with angiographically proven coronary heart disease (CHD, n=19), patients with idiopathic congestive heart failure (IDCM=idiopathic dilated cardiomyopathy, n=20), and transplant donors. Methods: Masson-Goldner staining and immunohistochemistry utilizing anti ox-LDL and CD68 were performed on paraffin sections of freshly isolated semilunar valves. Data were analyzed by digital image planimetry and by visual scoring of staining intensity. Results: Ox-LDL immunoreactivity was identified in the vascular aspect of the attachment line, in the deep valve stroma, and in the ventricular and vascular endothelium of the semilunar valves, colocalizing with macrophages. Valvular ox-LDL area was significantly increased in CHD-patients (P<0.03) and IDCM-patients (P<0.04) compared with controls. More ox-LDL was accumulating in the pulmonary valves than in the aortic valves (P=0.04) as assessed by area and staining intensity. Valvular ox-LDL area in pulmonary valve and aortic valve was significantly correlated with ox-LDL accumulation in the intimal layer (P<0.001) and medial layer (P<0.001) of coronary arteries from the same patients. Conclusion: The data suggest that the biological process lending to ox-LDL accumulation in coronary atherosclerosis also involves heart valves. Therefore, accumulation of the oxidative stress marker ox-LDL in heart valves illustrates atherosclerosis as an additional mechanism accelerating valvular degeneration in these patients. (C) 2000 Elsevier Science B.V. All rights reserved.