The Mechanism of Ligamentum Flavum Hypertrophy

Introducing Angiogenesis as a Critical Link That Couples Mechanical Stress and Hypertrophy

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10 Citations (Scopus)

Abstract

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
JournalNeurosurgery
Volume77
Issue number2
DOIs
Publication statusPublished - 2015 Jan 1

Fingerprint

Ligamentum Flavum
Mechanical Stress
Spinal Stenosis
Hypertrophy
Spinal Canal
Vascular Endothelial Growth Factor A
Angiogenesis Inducing Agents
Control Groups
Angiopoietin-1
Vascular Cell Adhesion Molecule-1
Fibroblast Growth Factor 2
Enzyme-Linked Immunosorbent Assay
Demography
Pathology
Inflammation

Keywords

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

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

@article{df3f1442c93447719c551d252b6f1963,
title = "The Mechanism of Ligamentum Flavum Hypertrophy: Introducing Angiogenesis as a Critical Link That Couples Mechanical Stress and Hypertrophy",
abstract = "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.",
keywords = "Angiogenesis, Inflammation, Ligamentum flavum hypertrophy, Lumbar spinal canal stenosis, Vascular endothelial growth factor",
author = "Hur, {Junseok W.} and Bum-Joon Kim and Park, {Jin Hyun} and Joo-Han Kim and Youn-Kwan Park and Taek-Hyun Kwon and Moon, {Hong Joo}",
year = "2015",
month = "1",
day = "1",
doi = "10.1227/NEU.0000000000000755",
language = "English",
volume = "77",
pages = "274--281",
journal = "Neurosurgery",
issn = "0148-396X",
publisher = "Lippincott Williams and Wilkins",
number = "2",

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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

PY - 2015/1/1

Y1 - 2015/1/1

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

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