title: Lack of the cysteine protease inhibitor cystatin C promotes atherosclerosis in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  Degradation of extracellular matrix plays an important role in growth and destabilization of atherosclerotic plaques. Cystatin C, inhibitor of the collagen- and elastin-degrading cysteine proteases of the cathepsin family, is produced by virtually all cell types. It is present in the normal artery wall but severely reduced in human atherosclerotic lesions.
  
  
  RESULTS
  To determine the functional role of cystatin C in atherosclerosis, we crossed cystatin C-deficient (cysC(-/-)) mice with apolipoprotein E-deficient (apoE(-/-)) mice. After 25 weeks of atherogenic diet, mice lacking apoE and cystatin C (cysC(-/-) apoE(-/-)) had larger subvalvular plaques compared with cysC(+/+) apoE(-/-) mice (766,000+/-20,000 microm2 per section versus 662,000+/-19,000 microm2 per section; P=0.001), suggesting an atheroprotective role of cystatin C. The plaques from cysC(-/-) apoE(-/-) mice were characterized by increased total macrophage content. To determine which cellular source is important for the antiatherosclerotic effect of cystatin C, we performed bone marrow transplantations. ApoE(-/-) mice were transplanted with either cysC(-/-) apoE(-/-) or cysC(+/+) apoE(-/-) bone marrow. No significant differences in plaque area, macrophage, collagen, or lipid content of subvalvular lesions between the 2 groups were detected.
  
  
  CONCLUSIONS
  The result suggests that the protective role of cystatin C in atherosclerosis is dependent primarily on its expression in nonhematopoietic cell types.
authors.affiliation: Department of Clinical Sciences, Malmö University Hospital, Lund University, Sweden. eva.bengtsson@med.lu.se
authors.forename: Eva
authors.initials: E
authors.lastname: Bengtsson
authors.forename: Fong
authors.initials: F
authors.lastname: To
authors.forename: Katarina
authors.initials: K
authors.lastname: Håkansson
authors.forename: Anders
authors.initials: A
authors.lastname: Grubb
authors.forename: Lena
authors.initials: L
authors.lastname: Brånén
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
authors.forename: Stefan
authors.initials: S
authors.lastname: Jovinge
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002784:Cholesterol / Q000097:blood; D003094:Collagen / Q000378:metabolism; D055316:Cystatin C; D015891:Cystatins / Q000235:genetics* / Q000378:metabolism*; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D001057:Apolipoproteins E; C525030:CST3 protein, human; C525031:Cst3 protein, mouse; D055316:Cystatin C; D015891:Cystatins; D003094:Collagen; D002784:Cholesterol