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

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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.

Original languageEnglish
Pages (from-to)274-281
Number of pages8
Issue number2
Publication statusPublished - 2015 Jan 1



  • Angiogenesis
  • Inflammation
  • Ligamentum flavum hypertrophy
  • Lumbar spinal canal stenosis
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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