Angiogenesis and blood vessel stability in inflammatory arthritis.

Hdl Handle:
http://hdl.handle.net/10147/207614
Title:
Angiogenesis and blood vessel stability in inflammatory arthritis.
Authors:
Kennedy, Aisling; Ng, Chin Teck; Biniecka, Monika; Saber, Tajvur; Taylor, Cormac; O'Sullivan, Jacintha; Veale, Douglas J; Fearon, Ursula
Affiliation:
Dublin Academic Health Care, St. Vincent's University Hospital and The Conway, Institute of Biomolecular and Biomedical Research, Dublin, Ireland.
Citation:
Arthritis Rheum. 2010 Mar;62(3):711-21.
Journal:
Arthritis and rheumatism
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207614
DOI:
10.1002/art.27287
PubMed ID:
20187131
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.
Language:
eng
MeSH:
Adult; Aged; Aged, 80 and over; Arthritis/pathology/*physiopathology; Blood Vessels/*physiopathology; Cell Hypoxia/physiology; DNA Damage/physiology; Humans; Immunohistochemistry; Inflammation; Middle Aged; Neovascularization, Pathologic; Neural Cell Adhesion Molecules/analysis; Oxygen/analysis; Synovial Membrane/*blood supply
ISSN:
1529-0131 (Electronic); 0004-3591 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorKennedy, Aislingen_GB
dc.contributor.authorNg, Chin Tecken_GB
dc.contributor.authorBiniecka, Monikaen_GB
dc.contributor.authorSaber, Tajvuren_GB
dc.contributor.authorTaylor, Cormacen_GB
dc.contributor.authorO'Sullivan, Jacinthaen_GB
dc.contributor.authorVeale, Douglas Jen_GB
dc.contributor.authorFearon, Ursulaen_GB
dc.date.accessioned2012-02-01T10:32:55Z-
dc.date.available2012-02-01T10:32:55Z-
dc.date.issued2012-02-01T10:32:55Z-
dc.identifier.citationArthritis Rheum. 2010 Mar;62(3):711-21.en_GB
dc.identifier.issn1529-0131 (Electronic)en_GB
dc.identifier.issn0004-3591 (Linking)en_GB
dc.identifier.pmid20187131en_GB
dc.identifier.doi10.1002/art.27287en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207614-
dc.description.abstractOBJECTIVE: 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAdulten_GB
dc.subject.meshAgeden_GB
dc.subject.meshAged, 80 and overen_GB
dc.subject.meshArthritis/pathology/*physiopathologyen_GB
dc.subject.meshBlood Vessels/*physiopathologyen_GB
dc.subject.meshCell Hypoxia/physiologyen_GB
dc.subject.meshDNA Damage/physiologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunohistochemistryen_GB
dc.subject.meshInflammationen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshNeovascularization, Pathologicen_GB
dc.subject.meshNeural Cell Adhesion Molecules/analysisen_GB
dc.subject.meshOxygen/analysisen_GB
dc.subject.meshSynovial Membrane/*blood supplyen_GB
dc.titleAngiogenesis and blood vessel stability in inflammatory arthritis.en_GB
dc.contributor.departmentDublin Academic Health Care, St. Vincent's University Hospital and The Conway, Institute of Biomolecular and Biomedical Research, Dublin, Ireland.en_GB
dc.identifier.journalArthritis and rheumatismen_GB
dc.description.provinceLeinster-

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