ABSTRACT
Cystatin C, an endogenous inhibitor of cathepsin proteases has emerged as a biomarker of cardiovascular risk and reduced renal function. Epidemiological studies indicate that serum cystatin C increased in human obesity. Here, we evaluated the contribution of adipose tissue to this elevation, based on our previous observation that cystatin C is produced by in vitro differentiated human adipocytes. We measured serum cystatin C in 237 nonobese (age: 51 +/- 0.8 years; BMI: 22.8 +/- 0.11 kg/m(2)) and 248 obese subjects (age: 50 +/- 0.8 years; BMI: 34.7 +/- 0.29 kg/m(2)). Creatinine-based estimated glomerular filtration rate (eGFR) was calculated to account for renal status. Cystatin C gene expression and secretion were determined on surgical adipose tissue biopsies in a distinct group of subjects. Serum cystatin C is elevated in obese subjects of both genders, independently of reduced eGFR. Cystatin C mRNA is expressed in subcutaneous and omental adipose tissue, at twice higher levels in nonadipose than in adipose cells. Gene expression and cystatin C release by adipose tissue explants increase two- to threefold in obesity. These data confirm elevation of serum cystatin C in human obesity and strongly argue for a contribution of increased production of cystatin C by enlarged adipose tissue. Because cystatin C has the potential to affect adipose tissue and vascular homeostasis through local and/or systemic inhibition of cathepsins, this study adds a new factor to the list of adipose tissue secreted bioactive molecules implicated in obesity and obesity-linked complications.
Subject(s)
Adipose Tissue/metabolism , Cystatin C/blood , Obesity/blood , Case-Control Studies , Cathepsins/antagonists & inhibitors , Cystatin C/genetics , Cystatin C/metabolism , Gene Expression , Humans , Obesity/metabolism , Omentum/metabolism , RNA, Messenger/metabolism , Reference Values , Subcutaneous Fat/metabolismABSTRACT
BACKGROUND: Many studies have demonstrated a gap between guidelines for the prevention of cardiovascular disease (CVD) and their implementation in clinical practice. AIM: The PEGASE education program has been devised with an aim to improve the management of patients at high risk of CVD. METHODS: In a multicentre study carried out from 2001-2004 in France, 96 participating physicians were randomized into a "trained" group, which included 398 "educated" patients, and a "non-trained" group, which included 242 "non-educated" patients. Educated patients received six hospital-based educational sessions, four collective and two individual. Framingham score, smoking, lipid levels, glycaemia, blood pressure, dietary intake and drug compliance, as well as quality of life, were evaluated at baseline (M0) and 6 months (M6). The primary endpoint of the study was the efficacy of the PEGASE program in reducing global CVD risk in high-risk patients. RESULTS: The Framingham score was calculated for 473 patients. The Framingham score improved significantly at M6 vs M0 in the educated group (13.0 +/- 8.21 vs 13.6 +/- 8.48, d = -0.658, p = 0.016), but not in the non-educated group (12.5 +/- 8.19 vs 12.4 +/- 7.81, d = +0.064, p = 0.836); the mean change between the two groups did not reach significance. Quality of life, LDL-c level and diet scores improved in the "educated" group only. CONCLUSIONS: The PEGASE education program improved risk factors for CVD, although global assessment by Framingham score was not significantly different between groups. This program, aimed at meeting needs and expectations of patients and physicians, was easily implemented in all hospital centres.
