Cystatin C deficiency increases elastic lamina degradation and aortic dilatation in apolipoprotein E-null mice.

Abstract:

:The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves substantial proteolysis of the arterial extracellular matrix. The lysosomal cysteine proteases can exert potent elastolytic and collagenolytic activity. Human atherosclerotic plaques have increased cysteine protease content and decreased levels of the endogenous inhibitor cystatin C, suggesting an imbalance that would favor matrix degradation in the arterial wall. This study tested directly the hypothesis that impaired expression of cystatin C alters arterial structure. Cystatin C-deficient mice (Cyst C-/-) were crossbred with apolipoprotein E-deficient mice (ApoE-/-) to generate cystatin C and apolipoprotein E-double deficient mice (Cyst C-/-ApoE-/-). After 12 weeks on an atherogenic diet, cystatin C deficiency yielded significantly increased tunica media elastic lamina fragmentation, decreased medial size, and increased smooth muscle cell and collagen content in aortic lesions of ApoE-/- mice. Cyst C-/-ApoE-/- mice also showed dilated thoracic and abdominal aortae compared with control ApoE-/- mice, although atheroma lesion size, intimal macrophage accumulation, and lipid core size did not differ between these mice. These findings demonstrate directly the importance of cysteine protease/protease inhibitor balance in dysregulated arterial integrity and remodeling during experimental atherogenesis.

journal_name

Circ Res

journal_title

Circulation research

authors

Sukhova GK,Wang B,Libby P,Pan JH,Zhang Y,Grubb A,Fang K,Chapman HA,Shi GP

doi

10.1161/01.RES.0000155964.34150.F7

subject

Has Abstract

pub_date

2005-02-18 00:00:00

pages

368-75

issue

3

eissn

0009-7330

issn

1524-4571

pii

01.RES.0000155964.34150.F7

journal_volume

96

pub_type

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