Synchronization of intra-articular power doppler flow and systemic angiogenic activitiy in arthritis as a new “in vivo“ model to study angiogenesis

Objectives: In rheumatoid arthritis (RA) vasodilation and synovial angiogenesis result in local intra-articular hyperemia which can be visualized by Doppler ultrasound. Since elevated angiogenic factors could be measured in the serum of RA patients, we evaluated a possible association with synovial microvascular power Doppler flow in a longitudinal study.

Patients and methods: Inflamed wrists of 15 RA patients were examined by ultrasound prior to and at days 3,7,14 and 42 after the initiation of a first-line treatment with Glucocorticoids or with TNF-alpha inhibitors. Besides the assessment of clinical and laboratory disease activity parameters, serum levels of VEGF, Angiogenin and TIMP-2 were measured by an ELISA. A linear array transducer was used to produce grey-scale images of synovitis and effusion as well as two- (2D) and three-dimensional (3D) power Doppler sonographic images and movies of synovial vascularity, which were quantified using a computerized count of volume pixels (voxel).

Results: Under both treatment regimes, a significant reduction of VEGF concentrations and the numbers of voxels could be determined (p=0.001) after six weeks, but no correlation was found between both (rho: p=0.7; r=-0.03). Angiogenin levels increased in the GC-group (+10%) and showed a slight decrease in the TNF-alpha group (-11% from pre-treatment values), whereas TIMP-2 did not change significantly in both groups.

Conclusion: The dissociation of serum angiogenic promoters and intra-articular synovial hyperemia during anti-inflammatory therapy may indicate that synovial perfusion is a more local than systemic driven process in rheumatoid inflammation.