Impact of serum high mobility group box 1 and soluble receptor for advanced glycation end-products on subclinical atherosclerosis in patients with granulomatosis with polyangiitis.
The objective of this study was to evaluate whether levels of high mobility group box 1 (HMGB1) in granulomatosis with polyangiitis (GPA) patients are associated with carotid atherosclerosis, related to levels of soluble receptor for advanced glycation end-products (sRAGE) and influenced by immunosuppressive or lipid-lowering therapy. Twenty-three GPA patients and 20 controls were evaluated for HMGB1- and sRAGE levels and for carotid atherosclerosis using ultrasound to determine intima-media thickness (IMT). In vitro the effect of atorvastatin on the production of HMGB1 by lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVEC) was assessed. Serum HMGB1 and sRAGE levels did not differ between patients and controls. A negative correlation was found between sRAGE and maximum IMT but HMGB1 and carotid IMT were not related. HMGB1 levels were reduced in GPA patients on statins and prednisolone. In vitro, atorvastatin reduced HMGB1 levels in supernatants of activated HUVEC. In conclusion, carotid IMT is inversely correlated with sRAGE levels but not with HMGB1 levels. Statins and prednisolone are associated with reduced serum HMGB1 levels and atorvastatin decreases HMGB1 release by activated HUVEC in vitro, indicating an additional anti-inflammatory effect of statins.
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Rheumatology Division, Universidade Federal de São Paulo/Escola Paulista de Medicina (Unifesp/EPM), São Paulo-SP, Brazil.
Alexandre W S de
AW
Souza
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Karina
K
de Leeuw
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Mirjan M
MM
van Timmeren
Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Pieter C
PC
Limburg
Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Coen A
CA
Stegeman
Martini Hospital, Groningen, The Netherlands.
Marc
M
Bijl
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Johanna
J
Westra
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Cees G M
CG
Kallenberg
D050197:Atherosclerosis / Q000097:blood* / Q000150:complications* / Q000188:drug therapy; D000069059:Atorvastatin; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000150:complications*; D024243:HMGB1 Protein / Q000097:blood*; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood* / Q000737:chemistry*; D012995:Solubility
D024243:HMGB1 Protein; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D011239:Prednisolone; D000069059:Atorvastatin