Expression of the cysteine protease legumain in vascular lesions and functional implications in atherogenesis
| Autor: | Leo M. Albert, James C. Keith, Kathleen M. Shields, Vasu Maganti, George P. Vlasuk, Jeffrey L. Feldman, Gustave T. Hebert, Debra D. Pittman, Heather H. Shih, Anthony Wong, Janet E. Paulsen, Aaron Winkler, Christine Resmini, Valerie Clerin, Nanhua Deng |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Apolipoprotein E Pathology medicine.medical_specialty Aortic Diseases In situ hybridization Legumain Monocytes Umbilical vein Mice Apolipoproteins E medicine Animals Humans Macrophage RNA Messenger biology Microarray analysis techniques Macrophages Age Factors Endothelial Cells Chemotaxis Atherosclerosis Cysteine protease Mice Inbred C57BL Cysteine Endopeptidases Disease Models Animal biology.protein Cancer research Female Cardiology and Cardiovascular Medicine |
| Zdroj: | Atherosclerosis. 201:53-66 |
| ISSN: | 0021-9150 |
| DOI: | 10.1016/j.atherosclerosis.2008.01.016 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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