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. METHODS AND 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.
OBJECTIVE: The present study was conducted to characterize the expression of the cysteine protease legumain in murine and humanatherosclerotic tissues, and to explore the molecular mechanisms by which legumain may contribute to the pathophysiology of atherosclerosis. METHODS AND 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 humancoronary 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 humanatherosclerotic 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: Marcin Poreba; Rigmor Solberg; Wioletta Rut; Ngoc Nguyen Lunde; Paulina Kasperkiewicz; Scott J Snipas; Marko Mihelic; Dusan Turk; Boris Turk; Guy S Salvesen; Marcin Drag Journal: Cell Chem Biol Date: 2016-07-28 Impact factor: 8.116
Authors: Kathleen M Eyster; Susan E Appt; Connie J Mark-Kappeler; Abha Chalpe; Thomas C Register; Thomas B Clarkson Journal: Menopause Date: 2011-10 Impact factor: 2.953
Authors: Laura E Edgington; Martijn Verdoes; Alberto Ortega; Nimali P Withana; Jiyoun Lee; Salahuddin Syed; Michael H Bachmann; Galia Blum; Matthew Bogyo Journal: J Am Chem Soc Date: 2012-12-18 Impact factor: 15.419