Dr. Veale has received consulting fees, speaking fees, and/or honoraria from GlaxoSmithKline, Wyeth, Opsona, Pfizer, and Centocor (less than $10,000 each).
Rheumatoid Arthritis Basic Science Studies
Angiogenesis and blood vessel stability in inflammatory arthritis
Article first published online: 25 FEB 2010
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 3, pages 711–721, March 2010
How to Cite
Kennedy, A., Ng, C. T., Biniecka, M., Saber, T., Taylor, C., O'Sullivan, J., Veale, D. J. and Fearon, U. (2010), Angiogenesis and blood vessel stability in inflammatory arthritis. Arthritis & Rheumatism, 62: 711–721. doi: 10.1002/art.27287
- Issue published online: 25 FEB 2010
- Article first published online: 25 FEB 2010
- Manuscript Accepted: 25 NOV 2009
- Manuscript Received: 1 MAY 2009
- Health Research Board of Ireland
- Science Foundation Ireland
To assess blood vessel stability in inflammatory synovial tissue (ST) and to examine neural cell adhesion molecule (NCAM), oxidative DNA damage, and hypoxia in vivo.
Macroscopic vascularity and ST oxygen levels were determined in vivo in patients with inflammatory arthritis who were undergoing arthroscopy. Vessel maturity/stability was quantified in matched ST samples by dual immunofluorescence staining for factor VIII (FVIII)/α-smooth muscle actin (α-SMA). NCAM and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) were examined by immunohistochemistry. Angiogenesis was assessed in vitro, using human dermal endothelial cells (HDECs) in a Matrigel tube formation assay.
A significant number of immature vessels (showing no pericyte recruitment) was observed in tissue from patients with inflammatory arthritis (P < 0.001), in contrast to osteoarthritic and normal tissue, which showed complete recruitment of pericytes. Low in vivo PO2 levels in the inflamed joint (median [range] 22.8 [3.2–54.1] mm Hg) were inversely related to increased macroscopic vascularity (P < 0.04) and increased microscopic expression of FVIII and α-SMA (P < 0.04 and P < 0.03, respectively). A significant proportion of vessels showed focal expression of NCAM and strong nuclear 8-oxodG expression, implicating a loss of EC–pericyte contact and increased DNA damage, levels of which were inversely associated with low in vivo PO2 (P = 0.04 for each comparison). Circulating cells were completely negative for 8-oxodG. Exposure of HDEC to 3% O2 (reflecting mean ST in vivo measurements) significantly increased EC tube formation (P < 0.05).
Our findings indicate the presence of unstable vessels in inflamed joints associated with hypoxia, incomplete EC–pericyte interactions, and increased DNA damage. These changes may further contribute to persistent hypoxia in the inflamed joint to further drive this unstable microenvironment.