title: Expression of the cysteine protease legumain in vascular lesions and functional implications in atherogenesis.
abstract: OBJECTIVE
  The present study was conducted to characterize the expression of the cysteine protease legumain in murine and human atherosclerotic tissues, and to explore the molecular mechanisms by which legumain may contribute to the pathophysiology of atherosclerosis.
  
  
  RESULTS
  Using microarray analysis, legumain mRNA expression was found to increase with development of atherosclerosis in the aorta of aging Apolipoprotein E deficient mice while expression remained at low level and unchanged in arteries of age-matched C57BL/6 control mice. In situ hybridization and immunohistochemical analysis determined that legumain was predominantly expressed by macrophages in the atherosclerotic aorta, in lesions at the aortic sinus and in injured carotid arteries of Apolipoprotein E deficient mice as well as in inflamed areas in advanced human coronary atherosclerotic plaques. In vitro, M-CSF differentiated human primary macrophages were shown to express legumain and the protein could also be detected in the culture media. When tested in migration assays, legumain induced chemotaxis of primary human monocytes and human umbilical vein endothelial cells.
  
  
  CONCLUSIONS
  Legumain is expressed in both murine and human atherosclerotic lesions. The macrophage-specific expression of legumain in vivo and ability of legumain to induce chemotaxis of monocytes and endothelial cells in vitro suggest that legumain may play a functional role in atherogenesis.
authors: Department of Cardiovascular and Metabolic Diseases, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA. vclerin@wyeth.com
authors: Valerie
authors: V
authors: Clerin
authors: Heather H
authors: HH
authors: Shih
authors: Nanhua
authors: N
authors: Deng
authors: Gustave
authors: G
authors: Hebert
authors: Christine
authors: C
authors: Resmini
authors: Kathleen M
authors: KM
authors: Shields
authors: Jeffrey L
authors: JL
authors: Feldman
authors: Aaron
authors: A
authors: Winkler
authors: Leo
authors: L
authors: Albert
authors: Vasu
authors: V
authors: Maganti
authors: Anthony
authors: A
authors: Wong
authors: Janet E
authors: JE
authors: Paulsen
authors: James C
authors: JC
authors: Keith
authors: George P
authors: GP
authors: Vlasuk
authors: Debra D
authors: DD
authors: Pittman
mesh_terms: D000367:Age Factors; D000818:Animals; D001018:Aortic Diseases / Q000201:enzymology* / Q000209:etiology* / Q000503:physiopathology; D001057:Apolipoproteins E / Q000502:physiology; D050197:Atherosclerosis / Q000201:enzymology* / Q000209:etiology* / Q000503:physiopathology; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology; D005260:Female; D006801:Humans; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D000099240:Asparaginyl Endopeptidase
chemical_list: D001057:Apolipoproteins E; D003546:Cysteine Endopeptidases; D012333:RNA, Messenger; D000099240:Asparaginyl Endopeptidase