title: Increased serum cathepsin S in patients with atherosclerosis and diabetes.
abstract: Atherosclerosis and diabetes are closely associated and both involve extensive degradation of the aortic elastin. Increased elastase activity has been detected in diabetic animal aortae. We have demonstrated enhanced elastolytic cathepsin S in human atherosclerotic lesions but insufficient amounts of its endogenous inhibitor cystatin C, suggesting alterations of serum cathepsin S and/or cystatin C in patients with atherosclerosis or diabetes. In this study, we measured levels of both cathepsin S and cystatin C in sera from 240 patients by ELISA. Among these patients, 107 had a diagnosis of atherosclerotic stenosis, 103 were diabetic, and 30 had neither condition. Multiple linear regression analysis demonstrated that significantly higher serum levels of cathepsin S in patients with either atherosclerotic stenosis (p<0.04) or diabetes (p=0.0005) persisted after adjustment for cystatin C level, renal function, smoking, and serum glucose levels (p=0.008, p=0.0005). Furthermore, patients with acute (p=0.009) or previous myocardial infarction (p<0.02) or unstable angina pectoris (p<0.05) had elevated levels of cathepsin S after adjustment for smoking, creatinine, cystatin C, and serum glucose. In contrast, serum cystatin C levels were higher in diabetic patients (p=0.00001), but not in atherosclerotic subjects (p=0.14), than in the non-involved population after adjustment for age, smoking, and renal function. Although the pathophysiology of cathepsin S or cystatin C in atherosclerosis and diabetes requires further investigation, increased serum cathepsin S may serve as a biomarker for both diseases.
authors.affiliation: Department of Molecular and Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Likun
authors.initials: L
authors.lastname: Ma
authors.forename: Jintian
authors.initials: J
authors.lastname: Yang
authors.forename: An
authors.initials: A
authors.lastname: Ren
authors.forename: Zimin
authors.initials: Z
authors.lastname: Sun
authors.forename: Gengxing
authors.initials: G
authors.lastname: Yan
authors.forename: Jiusong
authors.initials: J
authors.lastname: Sun
authors.forename: Huanxian
authors.initials: H
authors.lastname: Fu
authors.forename: Weihua
authors.initials: W
authors.lastname: Xu
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Hu
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shi
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002403:Cathepsins / Q000097:blood*; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D002403:Cathepsins; C028217:cathepsin S