Increased Expression of Vascular Endothelial Growth Factor is Associated with Hypertrophic Ligamentum Flavum in Lumbar Spinal Canal Stenosis

Abstract

Lumbar spinal canal stenosis (LSCS) is the most common spinal disorder in elderly patients, causing low back and leg pain, radiculopathy, and cauda equina syndrome. Vascular endothelial growth factor (VEGF) is a potent regulator of many cellular functions including proliferation, differentiation, wound healing, and angiogenesis. The present study aimed to investigate the pattern of VEGF expression in the ligamentum flavum (LF) of patients with LSCS. 24 patients with LSCS were recruited in this prospective study. We quantified and localized VEGF expression in LF tissues obtained during surgery. VEGF messenger RNA and protein expression in LF were determined using reverse transcription PCR (RT-PCR), and quantitative real-time PCR, immunohistochemistry, and ELISA. VEGF expression was significantly higher in the hypertrophic LF group than in the non-pathological LF group (p<0.01) as quantified by quantitative real-time PCR. Further ELISA analysis showed that the average concentration of VEGF in the hypertrophic LF was significantly elevated compared with that of controls (p<0.01). There was no correlation between the tissue VEGF expression of non-pathological LF and patient age in patients with LSCS. Moreover, the immunohistochemical study revealed that VEGF was positively stained on fibroblasts, inflammatory cells, and endothelial cells representing neovascularization within hypertrophic LF compared to the non-pathological LF of controls. The increased expression of VEGF was associated with the degenerative changes of hypertrophic LF, suggesting that VEGF could contribute to one of the mechanisms of pathogenesis in lumbar spinal stenosis.

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“…In recent years, the role of TGF-β1 has been suggested [16,17]. Another popular opinion is that angiogenesis represents a key step in the pathogenesis that follows mechanical stress during LFH development, and VEGF may play an important part in this process [18].…”

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“…Imunohistokemijski nađeno je pozitivno bojenje VEGF-om u stanicama endotela, fibroblastima i upalnim stanicama upozoravajući na neovaskularizaciju u hipertrofi čnima žutim ligamentima. 43 Spondilolisteza, odnosno iskliznuće jednog kralješka prema drugomu jedan je od uzroka stenoze spinalnog kanala slabinske regije, a najčešće je posljedica uznapredovalih degenerativnih promjena fasetnih zglobova i njihova subluksacijskog položaja, a u manjem broju slučajeva posljedica spondilolize, odnosno rascjepa luka kralješka. Spondilolisteza bez spondilolize dovodi do suženja centralnog kanala, lateralnih recesusa, a ako je snižena visina i.v.…”

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