on July 28, 2005
Published online before print July 28, 2005, doi: 10.1161/01.ATV.0000179600.34086.7d
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on April 11, 2005
Accepted on June 27, 2005
Lack of the Cysteine-Protease Inhibitor Cystatin C Promotes Atherosclerosis in Apolipoprotein E-Deficient Mice
Eva Bengtsson *;
From the Department of Clinical Sciences (E.B., F.T., L.B., J.N., S.J.), Malmö University Hospital, Sweden; the Department of Clinical Chemistry (A.G., K.H.) and the Department of Cardiology (S.J.), Coronary Program, Heart and Lung Division, Lund University Hospital, and Lund Strategic Research Center for Stem Cell Biology and Cell Therapy (S.J.), Lund University, Sweden.
* To whom correspondence should be addressed. E-mail: eva.bengtsson{at}med.lu.se.
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 µm2 per section versus 662 000±19 000 µm2 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.
Key words: atherosclerosis • genetically altered mice • macrophages • cystatin C
This article has been cited by other articles:
 |
|
 |
|
  N. Taglieri, W. Koenig, and J. C. Kaski Cystatin C and Cardiovascular Risk Clin. Chem., November 1, 2009; 55(11): 1932 - 1943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Yetkin and J. Waltenberger Cathepsin Enzymes and Cystatin C: Do They Play a Role in Positive Arterial Remodeling? Stroke, February 1, 2009; 40(2): e26 - e27. [Full Text] [PDF]
|
|
|
|
|
|
H. Kataoka Response to Letter by Yetkin and Waltenberger Stroke, February 1, 2009; 40(2): e28 - e28. [Full Text] [PDF]
|
|
|
|
|
|
T. Aoki, H. Kataoka, R. Ishibashi, K. Nozaki, and N. Hashimoto Cathepsin B, K, and S Are Expressed in Cerebral Aneurysms and Promote the Progression of Cerebral Aneurysms Stroke, September 1, 2008; 39(9): 2603 - 2610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. M. Lutgens, K. B. J. M. Cleutjens, M. J. A. P. Daemen, and S. Heeneman Cathepsin cysteine proteases in cardiovascular disease FASEB J, October 1, 2007; 21(12): 3029 - 3041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Novinec, R. N. Grass, W. J. Stark, V. Turk, A. Baici, and B. Lenarcic Interaction between Human Cathepsins K, L, and S and Elastins: MECHANISM OF ELASTINOLYSIS AND INHIBITION BY MACROMOLECULAR INHIBITORS J. Biol. Chem., March 16, 2007; 282(11): 7893 - 7902. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. W. Cheng, K. Obata, M. Kuzuya, H. Izawa, K. Nakamura, E. Asai, T. Nagasaka, M. Saka, T. Kimata, A. Noda, et al. Elastolytic Cathepsin Induction/Activation System Exists in Myocardium and Is Upregulated in Hypertensive Heart Failure Hypertension, November 1, 2006; 48(5): 979 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. O. Platt, R. F. Ankeny, and H. Jo Laminar Shear Stress Inhibits Cathepsin L Activity in Endothelial Cells Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1784 - 1790. [Abstract] [Full Text] [PDF]
|
|