Lack of the Cysteine-Protease Inhibitor Cystatin C Promotes Atherosclerosis in Apolipoprotein E-Deficient Mice.
(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:
https://lup.lub.lu.se/record/143067
- author
- Bengtsson, Eva LU ; To, Fong LU ; Håkansson, Katarina LU ; Grubb, Anders LU ; Brånén, Lena LU ; Nilsson, Jan LU and Jovinge, Stefan LU
- organization
- publishing date
- 2005
- 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
- Lippincott Williams & Wilkins
- external identifiers
-
- pmid:16051881
- wos:000232231500021
- scopus:26244446954
- ISSN
- 1524-4636
- DOI
- 10.1161/01.ATV.0000179600.34086.7d
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Hematopoietic Stem Cell Laboratory (013022012), Division of Clinical Chemistry and Pharmacology (013250300), Experimental Cardiovascular Research Unit (013242110)
- 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
- 2016-04-01 12:19:24
- date last changed
- 2023-02-21 05:46:23
@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}}, keywords = {{macrophages; genetically altered mice; cystatin C; atherosclerosis}}, language = {{eng}}, number = {{10}}, pages = {{2151--2156}}, publisher = {{Lippincott Williams & Wilkins}}, 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}}, doi = {{10.1161/01.ATV.0000179600.34086.7d}}, volume = {{25}}, year = {{2005}}, }