Angiogenesis and blood vessel stability in inflammatory arthritis.
dc.contributor.author | Kennedy, Aisling | |
dc.contributor.author | Ng, Chin Teck | |
dc.contributor.author | Biniecka, Monika | |
dc.contributor.author | Saber, Tajvur | |
dc.contributor.author | Taylor, Cormac | |
dc.contributor.author | O'Sullivan, Jacintha | |
dc.contributor.author | Veale, Douglas J | |
dc.contributor.author | Fearon, Ursula | |
dc.date.accessioned | 2012-02-01T10:32:55Z | |
dc.date.available | 2012-02-01T10:32:55Z | |
dc.date.issued | 2012-02-01T10:32:55Z | |
dc.identifier.citation | Arthritis Rheum. 2010 Mar;62(3):711-21. | en_GB |
dc.identifier.issn | 1529-0131 (Electronic) | en_GB |
dc.identifier.issn | 0004-3591 (Linking) | en_GB |
dc.identifier.pmid | 20187131 | en_GB |
dc.identifier.doi | 10.1002/art.27287 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10147/207614 | |
dc.description.abstract | OBJECTIVE: 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. METHODS: 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)/alpha-smooth muscle actin (alpha-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. RESULTS: 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 PO(2) 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 alpha-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 PO(2) (P = 0.04 for each comparison). Circulating cells were completely negative for 8-oxodG. Exposure of HDEC to 3% O(2) (reflecting mean ST in vivo measurements) significantly increased EC tube formation (P < 0.05). CONCLUSION: 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. | |
dc.language.iso | eng | en_GB |
dc.subject.mesh | Adult | en_GB |
dc.subject.mesh | Aged | en_GB |
dc.subject.mesh | Aged, 80 and over | en_GB |
dc.subject.mesh | Arthritis/pathology/*physiopathology | en_GB |
dc.subject.mesh | Blood Vessels/*physiopathology | en_GB |
dc.subject.mesh | Cell Hypoxia/physiology | en_GB |
dc.subject.mesh | DNA Damage/physiology | en_GB |
dc.subject.mesh | Humans | en_GB |
dc.subject.mesh | Immunohistochemistry | en_GB |
dc.subject.mesh | Inflammation | en_GB |
dc.subject.mesh | Middle Aged | en_GB |
dc.subject.mesh | Neovascularization, Pathologic | en_GB |
dc.subject.mesh | Neural Cell Adhesion Molecules/analysis | en_GB |
dc.subject.mesh | Oxygen/analysis | en_GB |
dc.subject.mesh | Synovial Membrane/*blood supply | en_GB |
dc.title | Angiogenesis and blood vessel stability in inflammatory arthritis. | en_GB |
dc.contributor.department | Dublin Academic Health Care, St. Vincent's University Hospital and The Conway, Institute of Biomolecular and Biomedical Research, Dublin, Ireland. | en_GB |
dc.identifier.journal | Arthritis and rheumatism | en_GB |
dc.description.province | Leinster | |
html.description.abstract | OBJECTIVE: 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. METHODS: 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)/alpha-smooth muscle actin (alpha-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. RESULTS: 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 PO(2) 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 alpha-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 PO(2) (P = 0.04 for each comparison). Circulating cells were completely negative for 8-oxodG. Exposure of HDEC to 3% O(2) (reflecting mean ST in vivo measurements) significantly increased EC tube formation (P < 0.05). CONCLUSION: 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. |