Ubiquitin-positive foam cells are identified in the aortic and mitral valves with atherosclerotic involvement.
OBJECTIVE
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. U+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.
Yamada
Tsutomu
T
Department of Pathology, Nihon University School of Medicine, Tokyo, Japan. tyamada@med.nihon-u.ac.jp
Satoh
Suetaka
S
Sueyoshi
Sumihisa
S
Mitsumata
Masako
M
Matsumoto
Taro
T
Ueno
Takahiro
T
Uehara
Kenji
K
Mizutani
Tomohiko
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000737:chemistry / Q000473:pathology*; D017209:Apoptosis; D050197:Atherosclerosis / Q000473:pathology*; D002114:Calcinosis; D005260:Female; D005355:Fibrosis; D005487:Foam Cells / Q000737:chemistry* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000737:chemistry / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex; D012720:Severity of Illness Index; D025801:Ubiquitin / Q000032:analysis*; D057149:Ubiquitinated Proteins / Q000032:analysis
D025801:Ubiquitin; D057149:Ubiquitinated Proteins; D046988:Proteasome Endopeptidase Complex