Ubiquitin-positive foam cells are identified in the aortic and mitral valves with atherosclerotic involvement

Abstract

Aim: Our aim was to determine the roles of the ubiquitin (Ub)-proteasome system (UPS) in valvular diseases by immunohistochemically identifying Ub-positive cells in aortic and mitral valves and determining if Ub+ cells were associated with the severity of valvular diseases. Methods: We evaluated surgically removed aortic and mitral valves from 60 patients (mean age, 64.5 years) for thickening, fibrosis, foam cell infiltration, thrombus, and atheromatous plaques by using grading scores. Ub+ cells were detected immunohistochemically. Results: We found Ub+ cells in 16 (26.7%) of the 60 patients. Eleven (28.2%) of the 39 aortic valves and 5 (23.8%) of the 21 mitral valves were Ub-positive. Ub was found with granular depositions in the cytoplasm of monocyte-derived foam cells that were CD68+. The aortic valvular thickness of the Ub+ group was significantly greater than that of the Ub- group (3.9 ± 1.6mm vs. 3.2 ± 1.6mm, p < 0.05). Foam cells and fibrosis were greater in the Ub+ group (p < 0.05), and calcifications were prominent in aortic valves. There was no difference in the number of apoptotic cells in Ub+ and Ub- groups. Ub+ cells were present in the affected valves and ubiquitinated proteins were accumulated in macrophage-derived foam cells. Conclusions: Ub+ foam cells are present in valves that are vulnerable to valvular disease, and UPS may contribute to the development of atherosclerosis through the inflammatory process.