TY - JOUR
T1 - The Mechanism of Ligamentum Flavum Hypertrophy
T2 - Introducing Angiogenesis as a Critical Link That Couples Mechanical Stress and Hypertrophy
AU - Hur, Junseok W.
AU - Kim, Bum Joon
AU - Park, Jin Hyun
AU - Kim, Joo Han
AU - Park, Youn Kwan
AU - Kwon, Taek Hyun
AU - Moon, Hong Joo
N1 - Publisher Copyright:
Copyright © 2015 by the Congress of Neurological Surgeons.
PY - 2015/8/20
Y1 - 2015/8/20
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Inflammation
KW - Ligamentum flavum hypertrophy
KW - Lumbar spinal canal stenosis
KW - Vascular endothelial growth factor
UR - http://www.scopus.com/inward/record.url?scp=84937391554&partnerID=8YFLogxK
U2 - 10.1227/NEU.0000000000000755
DO - 10.1227/NEU.0000000000000755
M3 - Article
C2 - 25850600
AN - SCOPUS:84937391554
SN - 0148-396X
VL - 77
SP - 274
EP - 281
JO - Neurosurgery
JF - Neurosurgery
IS - 2
ER -