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The role of SDF-1/CXCR4 in the vasculogenesis and remodeling of cerebral arteriovenous malformation.

Wang L, Guo S, Zhang N, Tao Y, Zhang H, Qi T, Liang F, Huang Z - Ther Clin Risk Manag (2015)

Bottom Line: Flow cytometry was used to quantify the level of circulating endothelial progenitor cells (EPCs).Large amounts of CXCR4-positive CD45(+) cells were found in brain AVM lesion blood vessel walls, which also have higher SDF-1 expression.The application of AMD3100 effectively suppressed angiogenesis and infiltration of CXCR4-positive CD45(+) cells in hypoperfusion rats compared to controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery ICU, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China.

ABSTRACT

Background: Cerebral arteriovenous malformation (AVM) involves the vasculogenesis of cerebral blood vessels and can cause severe intracranial hemorrhage. Stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, are believed to exert multiple physiological functions including angiogenesis. Thus, we investigated the role of SDF-1/CXCR4 in the vasculogenesis of cerebral AVM.

Methods: Brain AVM lesions from surgical resections were analyzed for the expression of SDF-1, CXCR4, VEGF-A, and HIF-1 by using immunohistochemical staining. Flow cytometry was used to quantify the level of circulating endothelial progenitor cells (EPCs). Further, in an animal study, chronic cerebral hypoperfusion model rats were analyzed for the expression of SDF-1 and HIF-1. CXCR4 antagonist, AMD3100, was also used to detect its effects on cerebral vasculogenesis and SDF-1 expression.

Results: Large amounts of CXCR4-positive CD45(+) cells were found in brain AVM lesion blood vessel walls, which also have higher SDF-1 expression. Cerebral AVM patients also had higher level of EPCs and SDF-1. In chronic cerebral hypoperfusion rats, SDF-1, HIF-1, and CD45 expressions were elevated. The application of AMD3100 effectively suppressed angiogenesis and infiltration of CXCR4-positive CD45(+) cells in hypoperfusion rats compared to controls.

Conclusion: The SDF-1/CXCR4 axis plays an important role in the vasculogenesis and migration of inflammatory cells in cerebral AVM lesions, possibly via the recruitment of bone marrow EPCs.

No MeSH data available.


Related in: MedlinePlus

CD45+ expression in chronic hypoperfusion mice.Notes: (A) Control; (B) 24 hours after surgery; (C) 7 days; (D) 42 days; and (E) 90 days after surgery. Magnification: ×400.
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f3-tcrm-11-1337: CD45+ expression in chronic hypoperfusion mice.Notes: (A) Control; (B) 24 hours after surgery; (C) 7 days; (D) 42 days; and (E) 90 days after surgery. Magnification: ×400.

Mentions: The MVD in the cerebral middle artery-feeding cortex was significantly higher in model rats at 7, 42, or 90 days when compared to that in sham group (Table 1, P<0.05 in all cases). The images of 18F-FDG PET/CT scan showed a dynamic change in cerebral intake of 18F-FDG in rats model as the SUVmax value significantly increased 24 hours after the surgery, and decreased at day 7, followed by increase at day 42 and day 90. Those values, however, were still lower than those of control or sham group (Table 2, P<0.05). The serum level of SDF-1α started to increase 24 hours after the surgery, reached a peak at day 7, and was still higher than control group at day 42 and day 90 (Table 3, P<0.05). A further IHC examination showed the presence of large amounts of CD45+ cells in cerebral tissues in model rats (Figure 3).


The role of SDF-1/CXCR4 in the vasculogenesis and remodeling of cerebral arteriovenous malformation.

Wang L, Guo S, Zhang N, Tao Y, Zhang H, Qi T, Liang F, Huang Z - Ther Clin Risk Manag (2015)

CD45+ expression in chronic hypoperfusion mice.Notes: (A) Control; (B) 24 hours after surgery; (C) 7 days; (D) 42 days; and (E) 90 days after surgery. Magnification: ×400.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562729&req=5

f3-tcrm-11-1337: CD45+ expression in chronic hypoperfusion mice.Notes: (A) Control; (B) 24 hours after surgery; (C) 7 days; (D) 42 days; and (E) 90 days after surgery. Magnification: ×400.
Mentions: The MVD in the cerebral middle artery-feeding cortex was significantly higher in model rats at 7, 42, or 90 days when compared to that in sham group (Table 1, P<0.05 in all cases). The images of 18F-FDG PET/CT scan showed a dynamic change in cerebral intake of 18F-FDG in rats model as the SUVmax value significantly increased 24 hours after the surgery, and decreased at day 7, followed by increase at day 42 and day 90. Those values, however, were still lower than those of control or sham group (Table 2, P<0.05). The serum level of SDF-1α started to increase 24 hours after the surgery, reached a peak at day 7, and was still higher than control group at day 42 and day 90 (Table 3, P<0.05). A further IHC examination showed the presence of large amounts of CD45+ cells in cerebral tissues in model rats (Figure 3).

Bottom Line: Flow cytometry was used to quantify the level of circulating endothelial progenitor cells (EPCs).Large amounts of CXCR4-positive CD45(+) cells were found in brain AVM lesion blood vessel walls, which also have higher SDF-1 expression.The application of AMD3100 effectively suppressed angiogenesis and infiltration of CXCR4-positive CD45(+) cells in hypoperfusion rats compared to controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery ICU, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China.

ABSTRACT

Background: Cerebral arteriovenous malformation (AVM) involves the vasculogenesis of cerebral blood vessels and can cause severe intracranial hemorrhage. Stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, are believed to exert multiple physiological functions including angiogenesis. Thus, we investigated the role of SDF-1/CXCR4 in the vasculogenesis of cerebral AVM.

Methods: Brain AVM lesions from surgical resections were analyzed for the expression of SDF-1, CXCR4, VEGF-A, and HIF-1 by using immunohistochemical staining. Flow cytometry was used to quantify the level of circulating endothelial progenitor cells (EPCs). Further, in an animal study, chronic cerebral hypoperfusion model rats were analyzed for the expression of SDF-1 and HIF-1. CXCR4 antagonist, AMD3100, was also used to detect its effects on cerebral vasculogenesis and SDF-1 expression.

Results: Large amounts of CXCR4-positive CD45(+) cells were found in brain AVM lesion blood vessel walls, which also have higher SDF-1 expression. Cerebral AVM patients also had higher level of EPCs and SDF-1. In chronic cerebral hypoperfusion rats, SDF-1, HIF-1, and CD45 expressions were elevated. The application of AMD3100 effectively suppressed angiogenesis and infiltration of CXCR4-positive CD45(+) cells in hypoperfusion rats compared to controls.

Conclusion: The SDF-1/CXCR4 axis plays an important role in the vasculogenesis and migration of inflammatory cells in cerebral AVM lesions, possibly via the recruitment of bone marrow EPCs.

No MeSH data available.


Related in: MedlinePlus