Cystatin C deficiency in human atherosclerosis and aortic aneurysms

The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves breakdown of the elastic laminae. Elastolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage, but whether endogenous local inhibitors counterbalance these proteases is unknown. We show here that, whereas cystatin C is normally expressed in vascular wall smooth muscle cells (SMCs), this cysteine protease inhibitor is severely reduced in both atherosclerotic and aneurysmal aortic lesions. Furthermore, increased abdominal aortic diameter among 122 patients screened by ultrasonography correlated inversely with serum cystatin C levels. In vitro, cytokine-stimulated vascular SMCs secrete cathepsins, whose elastolytic activity could be blocked when cystatin C secretion was induced by treatment with TGF-beta(1). The findings highlight a potentially important role for imbalance between cysteine proteases and cystatin C in arterial wall remodeling and establish that cystatin C deficiency occurs in vascular disease.

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kardiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cardiac and Cardiovascular Systems hsv//eng
Aorta/pathology
Aortic Aneurysm, Abdominal/metabolism
Arteries/metabolism
Arteriosclerosis/metabolism
Cells, Cultured
Cystatin C
Cystatins/blood
Cysteine Proteinase Inhibitors/blood
Dose-Response Relationship, Drug
Humans
Immunoblotting
Immunohistochemistry
Interferon-gamma/metabolism
Muscle, Smooth/metabolism
Transforming Growth Factor beta/metabolism

Sukhova, Galina K.Brigham and Women's Hospital / Harvard Medical School (author)
Grubb, AndersLund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cystatin C, njursjukdom, amyloidos och antibiotika,Forskargrupper vid Lunds universitet,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Cystatin C, renal disease, amyloidosis and antibiotics,Lund University Research Groups,Skåne University Hospital(Swepub:lu)kkem-agr (author)
Ducharme, AniqueBrigham and Women's Hospital / Harvard Medical School (author)
Rhode, Luis H.Brigham and Women's Hospital / Harvard Medical School (author)
Lee, Richard T.Brigham and Women's Hospital / Harvard Medical School (author)
Ridker, Paul M.Brigham and Women's Hospital / Harvard Medical School (author)
Libby, PeterBrigham and Women's Hospital / Harvard Medical School (author)
Chapman, Harold A.Brigham and Women's Hospital / Harvard Medical School (author)
Brigham and Women's Hospital / Harvard Medical SchoolAvdelningen för klinisk kemi och farmakologi (creator_code:org_t)

By the author/editor: Shi, Guo-Ping; Sukhova, Galina ...; Grubb, Anders; Ducharme, Anique; Rhode, Luis H.; Lee, Richard T.; show more...; Ridker, Paul M.; Libby, Peter; Chapman, Harold ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cardiac and Card ...

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