Proteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure.

Background: Heart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration.

Angiogenesis and blood vessel stability in inflammatory arthritis.

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).

Oxidative damage in synovial tissue is associated with in vivo hypoxic status in the arthritic joint.

Objectives: To assess levels of oxidative DNA damage (8-oxo-7,8-dihydro-2'-deoxyguanine; 8-oxo-dG) and lipid peroxidation (4-hydroxy-2-nonenal; 4-HNE) in serum, synovial fluid and tissue of patients with inflammatory arthritis in relation to in vivo hypoxia levels, disease activity and angiogenic markers.

Methods: Oxygen levels in synovial tissue were assessed using an oxygen/temperature probe. Nuclear and cytoplasmic 8-oxo-dG and 4-HNE levels were assessed in synovial tissue from 23 patients by immunohistochemistry.

Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures.

Objective: To investigate the role of oncostatin M (OSM) in cell adhesion, angiogenesis, and matrix degradation in rheumatoid arthritis (RA) synovial tissue and normal human cartilage.

Methods: Human dermal microvascular endothelial cell (HDMEC) and RA synovial fibroblast (RASF) proliferation and intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression were assessed by a bromodeoxyuridine proliferation assay and flow cytometry. HDMEC tubule formation and migration were assessed by Matrigel culture and migration assay.

Inhibition of angiogenic pathways in rheumatoid arthritis: potential for therapeutic targeting.

Angiogenesis is a significant and possibly primary event in the pathogenesis of inflammatory diseases including arthritis. Abnormalities of vascular morphology and angiogenesis have been described at the macroscopic, histological and molecular levels in the synovial membrane in rheumatoid, seronegative and degenerative arthritis. The vascular endothelium is an active organ that participates in the initiation and maintenance of the inflammatory response.

Angiogenesis in psoriasis and psoriatic arthritis: clues to disease pathogenesis.

Psoriasis is a common chronic dermatosis occurring in 2% of the population and associated with an inflammatory arthritis--psoriatic arthritis (PsA)--in up to 40% of cases. PsA accounts for approximately 15% of patients attending early synovitis clinics, therefore it represents the second most common diagnostic category after rheumatoid arthritis. There are a number of common pathogenic features that link the skin and the joint inflammatory processes.

COX inhibitors modulate bFGF-induced cell survival in MCF-7 breast cancer cells.

Basic fibroblast growth factor (bFGF) serves as a modulator of survival in breast cancer cells. The mechanisms by which bFGF transduces the anti-apoptotic signal and interacts with COX inhibitors were investigated. bFGF reduced apoptosis in MCF-7 breast cancer cells and up-regulated the expression of mitocondrial Bcl-2, whereas COX inhibitors meloxicam (selective COX-2) and aspirin (non-selective), induced apoptosis.