The Mechanism of Ligamentum Flavum Hypertrophy: Introducing Angiogenesis as a Critical Link That Couples Mechanical Stress and Hypertrophy.

BACKGROUND

Biochemical alterations associated with mechanical stress have been explored as an initiating step in the pathological progression of ligamentum flavum hypertrophy (LFH); however, this mechanism remains poorly understood. Recently, the inflammation induced after mechanical stress and the subsequent response of ligamentum flavum (LF) cells have been implicated in LFH pathology.

OBJECTIVE

To investigate the hypothesis that angiogenesis may be a critical link between hypertrophy and a series of stimulating events, including mechanical stress.

METHODS

LF from 20 lumbar spinal canal stenosis (LSCS) patients and 16 non-LSCS patients (control group) were collected during surgery. Patient demographic and radiographic data were obtained. The levels of angiogenic factors (vascular endothelial growth factor [VEGF], angiopoietin-1, vascular cell adhesion molecule, and basic fibroblast growth factor) in the LF were investigated by using an enzyme-linked immunosorbent assay. Angiogenesis was also quantified by immunohistochemical detection of CD34-positive capillaries. The correlations among clinical factors, including radiographic factors, angiogenic factors, and angiogenesis, were statistically analyzed.

RESULTS

The LSCS group was older and exhibited a longer symptom duration, wider segmental motion, and thicker LF than the control group. The LSCS group showed significantly higher tissue concentrations of VEGF (P < .001) that positively correlated with LF thickness (r = 0.557, P < .001) and segmental motion (r = 0.586, P < .001). The LSCS group showed significantly more CD34-positive capillaries than the control group (P = .004).

CONCLUSION

The LSCS group showed greater segmental motion, higher VEGF concentrations, and more CD34-positive capillaries than the control group. These data indicate that VEGF-mediated angiogenesis following mechanical stress may be a critical step within the series of pathological events in LFH.