Endothelial injury is closely related to osteopontin and TNF receptor-mediated inflammation in end-stage renal disease. (September 2019)

• Record Type: Journal Article
• Authors: Batko, Krzysztof; Krzanowski, Marcin; Gajda, Mariusz; Dumnicka, Paulina; Fedak, Danuta; Woziwodzka, Karolina; Sułowicz, Władysław; Kuźniewski, Marek; Litwin, Jan A.; Krzanowska, Katarzyna
• Is Part Of: Cytokine. Volume 121(2019)
• Publication Date: 2019-09
• Subjects: Thrombomodulin -- TNF receptors -- Osteopontin -- Inflammation -- Vascular remodelling -- End-stage renal disease; AVF arteriovenous fistula -- CKD chronic kidney disease -- CV cardiovascular -- Ca calcium -- EPC endothelial progenitor cells -- ESRD end stage renal disease -- FGF 23 fibroblast growth factor -- HD hemodialysis -- HGF hepatocyte growth factor -- IL interleukin -- hs CRP high sensitive C-reactive protein -- iPTH intact parathormone -- MAC medial artery calcification -- OC osteocalcin -- ON osteonectin -- OPG osteoprotegerin -- OPN osteopontin -- Pi phosphate -- PTX3 pentraxin 3 -- SMC smooth muscle cells -- sTM soluble thrombomodulin -- TNFR2 soluble tumor necrosis factor receptor type 2 -- RAC radial artery calcification TGF, β -transforming growth factor-β -- sVEGFR2 vascular endothelial growth factor receptor type 2 -- SDF1α stromal cell-derived factor 1α; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2019.05.016
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: sTM is a multifunctional molecule released following endothelial injury. sTM may be closely related to TNF-mediated inflammation in ESRD. OPN independently predicts sTM concentrations and may be involved in associated tissue remodeling and mineralization processes. sTM correlates with progression of MAC. sTM does not correlate with age and other traditional CV risk factors. Abstract: Background: Endothelial dysfunction, inflammation and active mineralization are key processes involved in cardiovascular burden in end stage renal disease (ESRD). Serum (soluble) thrombomodulin (sTM) is an established marker of endothelial injury. Patients: 80 patients in ESRD were recruited consecutively. Baseline distribution of sex, age, main comorbidities and Framingham score was similar. A biochemical panel including sTM, intact PTH (iPTH), interleukin-6 (IL-6), pentraxin 3 (PTX3), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteonectin (ON), soluble tumor necrosis factor receptor type 2 (TNFR2), transforming growth factor-β (TGF-β), hepatocyte growth factor (HGF), vascular endothelial growth factor receptor type 2 (sVEGFR2) and stromal cell-derived factor 1α (SDF1α) was investigated in each patient. Samples obtained while establishing haemodialysis (HD) access were stained for radial artery calcifications (RACs) with Alizarin red and examined histologically. Results: After adjustment for HD status, sTM showed a significant positive correlation with serum creatinine, TNFR2, OPN, HGF, SDF1α, sVEGFR2, Pi, iPTH, FGF-23, OPG, OC and ON. In forward stepwise multiple regression, serum creatinine, TNFR2, and OPN were identified as significant, independent predictors of sTM. Grades 1–3 of RACs correlated with sTM (R = 0.50, p = 0.017), while grade 3 RACs were significantly associated with higher sTM (p = 0.02) than less advanced lesions. Conclusion: Among novel renal and cardiovascular biomarkers, OPN and TNFR2 are closely related to sTM. This may link endothelial damage, vascular remodeling and inflammation. Progression of RAC parallels a presumed compensatory rise in sTM, reflecting endothelial injury. sTM has an intricate role in endothelial function and potential clinical and prognostic applications.