| Objective. To evaluate the clinical significance of serum level of hypoxia inducible factor-1α（HIF-1α）, vascular endothelial growth factor(VEGF), angiopoietin-1(Ang-1) and angiopoietin-2（Ang-2）inpatients with rheumatoid arthritis.Methods. The serum were collected from21healthy persons,24osteoarthritis patients and82rheumatoid arthritis patients. RA patients fulfilled the2009diagnostic criteria of the ACR/EULAR. Wedefined active and inactive group according to RA disease active score, while early active RA and lateactive RA group were defined on the basis of course of disease. There were28early active patients,32lateactive patients and22inactive patients with rheumatoid arthritis. Serum levels of HIF-1α, VEGF, Ang-1and Ang-2were measured with ELISA. We recorded CRP, ESR, anti-CCP antibody, tender jointcount(TJC), swollen joint count(SJC), and the28-joint Disease Activity Score(DAS28).At the same time29RA patients were examined with ultrasound, including bilateral shoulder, elbow, wrist,metacarpophalangeal(MCP), proximal interphalangeal(PIP) of the hands, and knee. Synovial hypertrophy(US joint count SH, US index SH), synovial fluid(US joint count SF, US index SF), resistance index andpower doppler signal（US joint PD,TSS）were scored at78synovial sites. The correlation wereanalyzed. We also detected the serum levels of HIF-1α, VEGF, Ang-1and Ang-2in25patients withactive RA after3month regular treatment. In addition we detected the synovial fluid levels of HIF-1α,VEGF, Ang-1and Ang-2, which included6RA patients and3disease controls(OA).Results.(1)The serum level of HIF-1α（0.52±0.13）ng/ml,VEGF（1284.71±271.71）pg/ml,Ang-1（0.55±0.25）ng/ml in patients with rheumatoid arthritis were higher than osteoarthritis patients（0.40±0.16）ng/ml,（934.40±80.28）pg/ml,（0.32±0.16）ng/mlandnormalcontrols（0.27±0.14）ng/ml,（564.68±115.30）pg/ml,（0.24±0.21）ng/ml, and the serum level of Ang-2（1.36±2.40）ng/mlwas higher than normal controls（0.52±0.32）ng/ml. The serum level of HIF-1α （0.97±0.23）ng/ml and VEGF（1354.54±194.44）pg/ml in early active patients was higher than late active patients（0.35±0.23）ng/ml,（1096.28±477.19）pg/mlandinactivepatients（0.25±0.17）ng/ml,（862.40±90.676）pg/ml.andVEGFinlateactivepatientswaswashigherthaninactivepatients.Theserum level of Ang-1in early active patients, late active patients and inactive patients with rheumatoidarthritis had no statistical significance.The serum level of Ang-2in inactive patients （2.05±1.95）ng/ml was significantly higher than late active patients（0.91±0.82）ng/ml.The serum level of HIF-1α, VEGFand Ang-1of before treatment were a little higher than of after treatment, but it had no statisticalsignificance. The serum level of Ang-2of after treatment was significantly higher than before.(2)Theserum level of HIF-1α was positive correlation with US joint SH, US index SH, US joint PD, but did notcorrelate with US joint SF, US index SF,TSS, RI. The serum level of VEGF was positive correlation withUS joint SH, US index SH, US joint PD, TSS, and was negative correlation with RI.The serum level ofAng-1was positive correlation with US joint SH, US joint PD and TSS, and was negative correlation withRI.The serum level of Ang-2did not correlate with US joint SH, US index SH, US joint SF, US index SF,US joint PD, US joint SF, US index SF. TSS and RI.(3)The serum level of HIF-1α did not correlate withCRP, ESR, anti-CCP antibody, TJC, SJC, DAS28;The serum level of VEGF had no correlation withCRP, ESR, anti-CCP antibody, TJC, SJC, DAS28;The serum level of Ang-1did not correlate with CRP,ESR, anti-CCP antibody, TJC, SJC, DAS28; The serum level of Ang-2did not correlate with CRP, ESR,anti-CCP antibody, TJC, SJC, DAS28.(4) In the active RA patients, the serum level of HIF-1α, VEGF,Ang-1and Ang-2was positive correlation with each other. In the inactive RA patients, the serum level ofHIF-1α was positive correlation with Ang-1, while the serum level of HIF-1α did not correlate withVEGF and Ang-2.VEGF, Ang-1and Ang-2did not correlate with each other.(5)The synovial fluid levelof HIF-1α, VEGF, Ang-1and Ang-2in RA patients was higher than in disease controls.(OA), but had nostatistical significance.Conclusion. The serum HIF-1α, VEGF, Ang-1and Ang-2could influence and promote each otherto mediate thickening and angiogenesis of synovium in RA. The serum of HIF-1α in early active patientswere high, and were positive correlation with synovial thickening. It showed that serum level of HIF-1αcorrelates with thickening of the synovium in early rheumatoid arthritis, and may be useful for earlydiagnosis.The serum VEGF and Ang-1level could be used as useful index to reflect RA synovialthickening and angiogenesis, and they could reflect active RA. The serum level of Ang-2were inverselycorrelated with RA disease activity index, and the serum level of Ang-2were significantly higher afterregular treatment, so it could be used as one of RA disease activity and curative effects index. |
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