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Lack of the Cysteine-Protease Inhibitor Cystatin C Promotes Atherosclerosis in Apolipoprotein E-Deficient Mice.

Bengtsson, Eva LU ; To, Fong LU ; Håkansson, Katarina LU ; Grubb, Anders LU ; Brånén, Lena LU ; Nilsson, Jan LU and Jovinge, Stefan LU (2005) In Arteriosclerosis, Thrombosis and Vascular Biology 25(10). p.2151-2156
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. Methods and 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 mu... (More)
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. Methods and 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 mu m(2) per section versus 662 000 +/- 19 000 mu m(2) 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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
macrophages, genetically altered mice, cystatin C, atherosclerosis
in
Arteriosclerosis, Thrombosis and Vascular Biology
volume
25
issue
10
pages
2151 - 2156
publisher
American Heart Association
external identifiers
  • pmid:16051881
  • wos:000232231500021
  • scopus:26244446954
ISSN
1524-4636
DOI
10.1161/01.ATV.0000179600.34086.7d
language
English
LU publication?
yes
id
376b7c07-9202-42c8-a963-05a88cbb9c71 (old id 143067)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16051881&dopt=Abstract
date added to LUP
2007-07-04 16:25:45
date last changed
2017-09-17 05:07:44
@article{376b7c07-9202-42c8-a963-05a88cbb9c71,
  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. Methods and 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 mu m(2) per section versus 662 000 +/- 19 000 mu m(2) 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.},
  author       = {Bengtsson, Eva and To, Fong and Håkansson, Katarina and Grubb, Anders and Brånén, Lena and Nilsson, Jan and Jovinge, Stefan},
  issn         = {1524-4636},
  keyword      = {macrophages,genetically altered mice,cystatin C,atherosclerosis},
  language     = {eng},
  number       = {10},
  pages        = {2151--2156},
  publisher    = {American Heart Association},
  series       = {Arteriosclerosis, Thrombosis and Vascular Biology},
  title        = {Lack of the Cysteine-Protease Inhibitor Cystatin C Promotes Atherosclerosis in Apolipoprotein E-Deficient Mice.},
  url          = {http://dx.doi.org/10.1161/01.ATV.0000179600.34086.7d},
  volume       = {25},
  year         = {2005},
}