Lack of the Cysteine-Protease Inhibitor Cystatin C Promotes Atherosclerosis in Apolipoprotein E-Deficient Mice.
Author
Summary, in English
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.
Department/s
Publishing year
2005
Language
English
Pages
2151-2156
Publication/Series
Arteriosclerosis, Thrombosis and Vascular Biology
Volume
25
Issue
10
Links
Document type
Journal article
Publisher
Lippincott Williams & Wilkins
Topic
- Cardiac and Cardiovascular Systems
Keywords
- macrophages
- genetically altered mice
- cystatin C
- atherosclerosis
Status
Published
Research group
- Cardiovascular Research - Immunity and Atherosclerosis
ISBN/ISSN/Other
- ISSN: 1524-4636