Relationship of angiogenic factors to disease activity and radiographic damage in rheumatoid arthritis.
OBJECTIVE
To determine the association between angiogenic factor mRNA expression and disease activity and radiographic damage in patients with rheumatoid arthritis (RA).


METHODS
We enrolled 42 RA patients and assessed their disease activity (DAS28) and Larsen scores. We used a semi-quantitative reverse transcriptase-polymerase chain reaction to measure levels of angiogenin, endoglin, survivin and angiomotin mRNA in peripheral blood mononuclear cells (PBMCs) from 42 patients and in fibroblasts-like synoviocytes (FLS) from 14 RA patients. Then, we compared the angiogenic factor mRNA expression levels and parameters for disease activity and radiographic damage between RA patients and 42 healthy controls. We also compared the mRNA levels from FLS between 14 RA patients and 12 osteoarthritis (OA) patients.


RESULTS
PBMCs from RA patients showed increased expression of survivin and angiomotin mRNA compared to controls, while rheumatoid FLS showed increased expression for all genes tested compared to OA FLS. Angiogenin, endoglin, and angiomotin mRNA levels of PBMCs did not show any significant correlation with DAS28, but the survivin mRNA level in PBMCs showed a significant positive correlation with DAS28 (p=0.003) and Larsen scores (p=0.012). Survivin was the only angiogenic factor that showed a significant association with the Larsen score.


CONCLUSIONS
The systemic and local production of angiogenic factors are increased in patients with RA and, of the genes tested in this study, survivin gene expression correlated well with disease activity and radiographic damage in patients with RA.
Park
M-C
MC
Division of Rheumatology, Department of Internal Medicine, Institute for Immunology and Immunologic Diseases, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. mcpark@yumc.yonsei.ac.kr
Chung
S-J
SJ
Park
Y-B
YB
Lee
S-K
SK
D043925:Angiogenesis Inducing Agents / Q000097:blood*; D000091082:Angiomotins; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000000981:diagnostic imaging* / Q000235:genetics; D016022:Case-Control Studies; D000071063:Endoglin; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010003:Osteoarthritis / Q000235:genetics; D012333:RNA, Messenger / Q000276:immunology / Q000378:metabolism; D011859:Radiography; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D000077022:Survivin; D013583:Synovial Membrane / Q000378:metabolism
C423985:AMOT protein, human; D043925:Angiogenesis Inducing Agents; D000091082:Angiomotins; D015703:Antigens, CD; C107489:BIRC5 protein, human; C064206:ENG protein, human; D000071063:Endoglin; D051034:Inhibitor of Apoptosis Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000077022:Survivin; C046366:angiogenin; D012259:Ribonuclease, Pancreatic