Abstract
Purpose: To investigate the relationships between vascular endothelial growth factor (VEGF), a proliferation marker (Ki-67) and the cell cycle inhibitor p27 (cyclin-dependent kinase inhibitor p27), in endothelial cells in chronic degeneration of the rotator cuff.
Background: The rotator cuff is subject to constant pressure from the head of the humerus. This tends to ‘wring out’ the blood supply resulting in a functionally avascular critical zone, although microvessels can be identified. This zone is the site of degeneration and tears. Attempts at repair under these circumstances could be compromised by inadequate local function of the vascular system particularly sprouting of the capillaries to support the repair process.
Methods: Rotator cuff tissue was obtained from ten patients (age 40–80y) undergoing surgical repair. The size of tear was 1–4.5cm, time from presentation to surgery was 1 month (acute) to between 0.5–4y (chronic). Immunohistochemical staining with commercial mono-clonal antibodies to VEGF, p27, Ki-67 was performed on formalin fixed paraffin embedded tissues. Endothelial cells were identified by CD31 and smooth muscle actin (SMA) positivity. Visualisation used a standard DAB chromagen technique.
Results: Microvessel distribution varied according to tissue location, being pronounced towards the muscle insertion and torn edges of tissue, but much reduced in areas of healthy tendon and absent from areas with clear signs of advanced matrix degeneration without tears. Widespread VEGF positivity was observed in fibroblast and endothelial cell populations and diffusely within the matrix. Strong P27 positivity was observed in many endothelial cells which consequently demonstrated little Ki-67 staining.
Conclusion: Thus the endothelial cells appear to be simultaneously under both a mitogenic, VEGF drive, and subject to an inhibition of proliferation i.e. p27 positivity.
The abstracts were prepared by David Stanley. Correspondence should be addressed to him c/o British Orthopaedic Association, Royal College of Surgeons, 35–43 Lincoln’s Inn Fields, London WC2A 3PN.
