Relationship between serum vascular cell adhesion molecule-1 and endothelin-1 levels with organ involvement and disease activity in systemic lupus erythematosus patients
Restricted accessResearch articleFirst published online October, 2018
Relationship between serum vascular cell adhesion molecule-1 and endothelin-1 levels with organ involvement and disease activity in systemic lupus erythematosus patients
Endothelial dysfunction plays an important role in pathogenesis of systemic lupus erythematosus (SLE). Considering the importance of serum soluble vascular cell adhesion molecule-1 as the most abundant of the circulating adhesion molecules increased as a result of endothelial dysfunction and the role of endothelin-1 in pathophysiology of SLE, this study aimed to evaluate serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels in SLE patients compared to healthy subjects.
Methods
In this cross-sectional study, 60 SLE patients according to the Systemic Lupus International Collaborating Clinics classification criteria for SLE and 40 age and sex-matched healthy controls were included. In patients, clinical examination was performed and SLE disease activity index was assessed. Serum endothelin-1 and soluble vascular cell adhesion molecule-1 levels were measured using ELISA kits.
Results
The mean ± standard deviation age of patients and controls was 31.91 ± 7.66 and 33.20 ± 10.08 years, respectively. Compared to healthy controls, serum soluble vascular cell adhesion molecule-1 (1023.8 ± 352.96 vs. 866.06 ± 109.91) and endothelin-1 (77.83 ± 16.27 vs. 54.45 ± 12.01) was significantly higher in SLE patients (P = 0.003 and P < 0.001, respectively). The most common organs involved in patients were skin, joint and kidney. There were no significant differences in serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels according to organ involvement, activity of disease and the conventional serum markers of disease activity (P > 0.05). There was no significant correlation between disease activity, organ involvement and negative or positivity of autoantibodies as well as serum complement with endothelin-1 and vascular cell adhesion molecule-1 levels (P > 0.05).
Conclusions
Although our study revealed higher serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels in SLE patients compared to healthy controls, there were no significant correlations between their serum levels with organ involvement and disease activity.
MinamiYHirabayashiYNagataCIshiiTHarigaeHSasakiT. Intakes of vitamin B6 and dietary fiber and clinical course of systemic lupus erythematosus: a prospective study of Japanese female patients. J Epidemiol2011, pp. 21246–254.
2.
Enrique GómezFKaufer-HorwitzMMancera-ChávezGEMedical Nutrition Therapy for Rheumatic Disease. In: MahanLKRaymondJL (eds). Krause's Food and The Nutrition Care Process, 14th ed. Philadelphia, PA: Saunders, 2016, pp. 790–812.
3.
HalbergP. Survival and causes of death in patients with systemic lupus erythematosus. Clin Rheumatol1991; 10: 367–368.
4.
AsanumaYOeserAShintaniAKet al.Premature coronary-artery atherosclerosis in systemic lupus erythematosus. N Engl J Med2003; 349: 2407–2415.
5.
El-MagadmiMBodillHAhmadYet al.Systemic lupus erythematosus: an independent risk factor for endothelial dysfunction in women. Circulation2004; 110: 399–404.
6.
UrowitzMBBookmanAAKoehlerBEGordonDASmytheHAOgryzloMA. The bimodal mortality pattern of systemic lupus erythematosus. Am J Med1976; 60: 221–225.
7.
PoberJSSessaWC. Evolving functions of endothelial cells in inflammation. Nat Rev Immunol2007; 7: 803–815.
BevilacquaMPStengelinSGimbroneMAJrSeedB. Endothelial leukozyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science1989; 243: 1160–1165.
10.
SeronDCameronJSHaskardDO. Expression of VCAM-1 in normal and diseased kidney. Nephrol Dial Transplant1991; 6: 917–922.
11.
ClarkEAGrabsteinKHShuGL. Cultured human follicular dendritic cells. Growth characteristics and interactions with B lymphocytes. J Immmunol1992; 148: 3327–3335.
12.
WilkinsonLSEdwardsJCPostonRNHaskardDO. Expression of vascular cell adhesion molecule-1 in normal and inflamed synovium. Lab Investig1993; 68: 82–88.
13.
YamaneKIhnHKuboM. Increased serum levels of souble vascular cell adhesion molecule 1 and E-selectin in patients with localized scleroderma. J Am Acad Dermatol2000; 42: 64–69.
14.
KaplanskiGCacoubPFarnarierCet al.Increased soluble vascular cell adhesion molecule 1 concentrations in patients with primary or systemic lupus erythematosus-related antiphospholipid syndrome: correlations with the severity of thrombosis. Arthritis Rheum2000; 43: 55–64.
15.
BecvárRStorkJPesákováVet al.Clinical correlations of potential activity markers in systemic sclerosis. Ann NY Acad Sci2005; 1051: 404–412.
16.
Navarro-HernándezREOregon-RomeroEVázquez-Del MercadoMRangel-VillalobosHPalafox-SánchezCAMuñoz-ValleJF. Expression of ICAM1 and VCAM1 serum levels in rheumatoid arthritis clinical activity. Association with genetic polymorphisms. Dis Markers2009; 26: 119–126.
17.
GruschwitzMSHornsteinOPvon Den DrieschP. Correlation of soluble adhesion molecules in the peripheral blood of scleroderma patients with their in situ expression and with disease activity. Arthritis Rheum1995; 38: 184–189.
18.
JulkunenHSaijonmaaOGrönhagen-RiskaCTeppoAMFyhrquistF. Raised plasma concentrations of endothelin-1 in systemic lupus erythematosus. Ann Rheum Dis1991; 50: 526–527.
19.
TamLSLiEKTomlinsonB. Premature atherosclerosis in systemic lupus erythematosus: pathogenesis and therapeutic considerations. Hong Kong J Nephrol2006; 8: 48–54.
20.
GoldieRGKnottPGCarrMJHayDWHenryPJ. The endothelins in the pulmonary system. Pulm Pharmacol1996; 9: 69–93.
21.
ShiwenXLeaskAAbrahamDJFonsecaC. Endothelin receptor selectivity: evidence from in vitro and pre-clinical models of scleroderma. Eur J Clin Invest2009; 39(Suppl. 2): 19–26.
22.
Kuryliszyn-MoskalAKlimiukPACiolkiewiczMSierakowskiS. Clinical significance of selected endothelial activation markers in patients with systemic lupus erythematosus. J Rheumatol2008; 35: 1307–1313.
23.
TanEMCohenASFriesJFet al.The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum1982; 25: 1271–1277.
DieudeMSenecalJLRaymondY. Induction of endothelial cell apoptosis by heat-shock protein 60-reactive antibodies from anti-endothelial cell autoantibody-positive systemic lupus erythematosus patients. Arthritis Rheum2004; 50: 3221–3231.
32.
CarvalhoDSavageCOIsenbergDPearsonJD. IgG antiendothelial cell autoantibodies from patients with systemic lupus erythematosus or systemic vasculitis stimulate the release of two endothelial cell-derived mediators, which enhance adhesion molecule expression and leukocyte adhesion in an autocrine manner. Arthritis Rheum1999; 42: 631–640.
33.
KondoATakahashiKMizunoTet al.The level of IgA antibodies to endothelial cells correlates with histological evidence of disease activity in patients with lupus nephritis. PLoS One2016; 11: e0163085.
34.
AndersonTJ. Assessment and treatment of endothelial dysfunction in humans. J Am Coll Cardiol1999; 34: 631–638.
SodergrenAKarpKBomanKet al.Atherosclerosis in early rheumatoid arthritis: very early endothelial activation and rapid progression of intima media thickness. Arthritis Res Ther2010; 12: R158.
37.
TousoulisDAntoniadesCStefanadisC. Assessing inflammatory status in cardiovascular disease. Heart2007; 93: 1001–1007.
38.
GearingAJNewmanW. Circulating adhesion molecules in disease. Immunol Today1993; 14: 506–512.
HajialiloMNoorabadiPTahsini TekantapehSMalek MahdaviA. Endothelin‐1, α‐Klotho, 25(OH) Vit D levels and severity of disease in scleroderma patients. Rheumatol Int2017; 37: 1651–1657.
41.
JanssenBALuqmaniRAGordonCet al.Correlation of blood levels of soluble vascular cell adhesion molecule-1 with disease activity in systemic lupus erythematosus and vasculitis. Br J Rheumatol1994; 33: 1112–1116.
42.
SpronkPEBootsmaHHuitemaMGLimburgPCKallenbergCG. Levels of soluble VCAM-1, soluble ICAM-1, and soluble E-selectin during disease exacerbations in patients with systemic lupus erythematosus (SLE); a long term prospective study. Clin Exp Immunol1994; 97: 439–444.
43.
HorakPScudlaVHermanovoZet al.Clinical utility of selected disease activity markers in patients with systemic lupus erythematosus. Clin Rheumatol2001; 20: 337–344.
44.
HoCYWongCKLiEKTamLSLamCW. Elevated plasma concentrations of nitric oxide, soluble thrombomodulin and soluble vascular cell adhesion molecule-1 in patients with systemic lupus erythematosus. Rheumatology (Oxford)2003; 42: 117–122.
45.
IkedaYFujimotoTAmenoMShiikiHDohiK. Relationship between lupus nephritis activity and the serum level of soluble VCAM-1. Lupus1998; 7: 347–354.
46.
LewisMJVyseSShieldsAMet al.Improved monitoring of clinical response in systemic lupus erythematosus by longitudinal trend in soluble vascular cell adhesion molecule-1. Arthritis Res Ther2016; 18: 1–11.
47.
KlimiukPAFiedorczykMSierakowskiSChwieckoJ. Soluble cell adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) in patients with early rheumatoid arthritis. Scand J Rheumatol2007; 36: 345–350.
48.
MatsudaJTsukamotoMGohchiKSaitohNMiyajimaYKazamaM. Effect of total-body cold exposure on plasma concentrations of von Willebrand factor, endothelin-1 and thrombomodulin in systemic lupus erythematosus patients with or without Raynaud's phenomenon. Acta Haematol1992; 88: 189–193.
49.
YoshioTMasuyamaJMimoriATakedaAMinotaSKanoS. Endothelin-1 release from cultured endothelial cells induced by sera from patients with systemic lupus erythematosus. Ann Rheum Dis1995; 54: 361–365.
50.
TydenHLoodCGullstrandBet al.Endothelial dysfunction is associated with activation of the type I interferon system and platelets in patients with systemic lupus erythematosus. RMD Open2017; 3: 1–8.
51.
Franchi Santos LFStadtloberNPCosta Dall'Aqua1LGScavuzziBMGuimarãesPMFlauzinoT. Increased adhesion molecule levels in systemic lupus erythematosus: relationships with severity of illness, autoimmunity, metabolic syndrome and cortisol levels. Lupus2018; 27: 380–388.
52.
MoladYMiroshnikESulkesJPitlikSWeinbergerAMonseliseY. Urinary soluble VCAM-1 in systemic lupus erythematosus: a clinical marker for monitoring disease activity and damage. Clin Exp Rheumatol2002; 20: 403–406.
53.
KianiANWuTFangHet al.Urinary vascular cell adhesion molecule, but not neutrophil gelatinase-associated lipocalin, is associated with lupus nephritis. J Rheumatol2012; 39: 1231–1237.
54.
SinghSWuTXieCet al.Urine VCAM-1 as a marker of renal pathology activity index in lupus nephritis. Arthritis Res Ther2012; 14: R164.
55.
LewisMJVyseSShieldsAMet al.Improved monitoring of clinical response in systemic lupus erythematosus by longitudinal trend in soluble vascular cell adhesion molecule-1. Arthritis Res Ther2016; 18: 5.
56.
Kuryliszyn-MoskalACiolkiewiczMKlimiukPASierakowskiS. Clinical significance of nailfold capillaroscopy in systemic lupus erythematosus: correlation with endothelial cell activation markers and disease activity. Scand J Rheumatol2009; 38: 38–45.
57.
BertsiasGCerveraRBoumpasDT. Systemic lupus erythematosus: pathogenesis and clinical features. EULAR textbook on rheumatic diseases, London: BMJ, 2012, pp. 476–505.
58.
HejaziEZWerthVP. Cutaneous lupus erythematosus: an update on pathogenesis, diagnosis and treatment. Am J Clin Dermatol2016; 17: 135–146.
59.
MikdashiJA. Altered functional neuronal activity in neuropsychiatric lupus: a systematic review of the fMRI investigations. Semin Arthritis Rheum2016; 45: 455–462.
60.
LalwaniPSouzaGKBBLimaDSNPassosLFBoechatALLimaES. Serum thiols as a biomarker of disease activity in lupus nephritis. PLoS One2015; 10: 1–12.
61.
DhaunNLilitkarntakulPMacintyreIMet al.Urinary endothelin-1 in chronic kidney disease and as a marker of disease activity in lupus nephritis. Am J Physiol Renal Physiol2009; 296: F1477–F1483.
