Proteoglycan/glycosaminoglycan and collagen content in the arterial wall of patients with end-stage renal disease: new indicators of vascular disease.

Abstract

The prevalence of cardiovascular (CV) comorbidity in patients with chronic kidney disease (CKD) is high, particularly in end‑stage renal disease (ESRD). There is an ongoing search for novel biomarkers of CV disease in this population. We aimed to investigate the associations of matrix proteoglycans (PGs) and glycosaminoglycans (GAGs), collagen, and arterial calcifications with selected serum and plasma markers of endothelial dysfunction, inflammation, oxidative stress, and bone turnover in patients with ESRD. We enrolled 47 adult patients (32 men) with stage 5 CKD. The following parameters were investigated: fibrinogen, soluble thrombomodulin (sTM), plasminogen activator inhibitor 1 (PAI‑1), stromal cell‑derived factor 1α (SDF‑1α), calcium (Ca), phosphate (Pi), intact parathormone, interleukin 6, high‑sensitivity C‑reactive protein (hs‑CRP), ferric reducing ability of plasma, 2,2‑diphenyl‑1‑picrylhydrazyl scavenging, ferric reducing ability of ascorbate in plasma, fetuin‑A, fibroblast growth factor 23, osteopontin, osteoprotegerin, osteocalcin, transforming growth factor β (TGF‑β), hepatocyte growth factor, secreted protein acidic and rich in cysteine, as well as matrix metalloproteinase 2. Radial artery specimens were stained with alizarin red for calcifications, alcian blue for PGs and GAGs, and sirius red for collagen. We observed positive correlations between PG and GAG, collagen, and calcification staining. The most intense (grade 3) alcian blue staining was significantly correlated with diabetes as well as higher levels of Ca × Pi product, hs‑CRP, fibrinogen, SDF‑1α, PAI‑1, and sTM. However, PAI‑1 was the only significant predictor of grade 3 alcian blue staining in a multiple logistic regression model adjusted for hemodialysis, Ca× Pi product, and hs‑CRP levels. Coagulation disorders and endothelial dysfunction are the hallmarks of ESRD. The levels of SDF‑1α, PAI‑1, sTM, and fibrinogen may be novel predictors of early vascular wall alterations and may serve as CV risk markers.