title: Absence of the protease inhibitor cystatin C in inflammatory cells results in larger plaque area in plaque regression of apoE-deficient mice.
abstract: Matrix remodelling plays an important role in regulating plaque stability. Cystatin C, an inhibitor of the elastin-degrading cysteine proteases of the cathepsin family, is believed to be one of the key protease inhibitors in this process. The aim of the present study was to investigate the role of leukocyte-specific cystatin C expression under conditions that favour plaque regression. Apolipoprotein E-deficient mice (apoE-/-) were given a Western-type diet 15 weeks prior transplantation with bone marrow from mice lacking cystatin C (cysC-/-) or cystatin C positive (cysC+/+) mice, in both cases apoE+/+ to create conditions favouring plaque regression. Transplantations were verified with PCR and Western analyses. Transplanted mice showed a 70% decrease in lipid content and reduction in plaque area compared to baseline ApoE-/- mice, demonstrating plaque regression due to apoE expression in macrophages. apoE-/- mice transplanted with cysC-/- bone marrow were then compared to mice transplanted with cysC+/+ bone marrow. Mice receiving cysC-/- bone marrow had a 30% larger plaque area, despite absence of significant differences in plasma cholesterol and lipid contents in plaque. Unexpectedly, mice transplanted with cystatin C-deficient bone marrow cells had increased elastin and collagen content in lesions. These observations suggest that leukocyte-specific expression of cystatin C is actively involved in matrix remodelling associated with plaque regression.
authors.affiliation: Department of Medicine, Section for Experimental Cardiovascular Research, Malmö University Hospital, Lund University, 205 02 Malmö, Sweden. eva.bengtsson@medforsk.mas.lu.se
authors.forename: Eva
authors.initials: E
authors.lastname: Bengtsson
authors.forename: Fong
authors.initials: F
authors.lastname: To
authors.forename: Anders
authors.initials: A
authors.lastname: Grubb
authors.forename: Katarina
authors.initials: K
authors.lastname: Håkansson
authors.forename: Lena
authors.initials: L
authors.lastname: Wittgren
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
authors.forename: Stefan
authors.initials: S
authors.lastname: Jovinge
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001391:Azo Compounds; D016026:Bone Marrow Transplantation; D002784:Cholesterol / Q000097:blood; D003094:Collagen / Q000378:metabolism; D004396:Coloring Agents; D055316:Cystatin C; D015891:Cystatins / Q000235:genetics* / Q000378:metabolism*; D004041:Dietary Fats / Q000494:pharmacology; D004549:Elastin / Q000378:metabolism; D005260:Female; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000378:metabolism / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D001391:Azo Compounds; D004396:Coloring Agents; C525031:Cst3 protein, mouse; D055316:Cystatin C; D015891:Cystatins; D004041:Dietary Fats; D003094:Collagen; D004549:Elastin; D002784:Cholesterol; C011049:oil red O