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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

EPCs from peripheral blood.Notes: This figure showed flow cytometry results of AVM patients (A); in controls (B). Left panels, raw images; middle panels, CD133+/CD34+ double-positive cells (upper right quadrant); and right panels, CD133+/CD34+/KDR+ triple-positive cells (upper right quadrant).Abbreviations: EPCs, endothelial progenitor cells; AVM, arteriovenous malformation.
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f2-tcrm-11-1337: EPCs from peripheral blood.Notes: This figure showed flow cytometry results of AVM patients (A); in controls (B). Left panels, raw images; middle panels, CD133+/CD34+ double-positive cells (upper right quadrant); and right panels, CD133+/CD34+/KDR+ triple-positive cells (upper right quadrant).Abbreviations: EPCs, endothelial progenitor cells; AVM, arteriovenous malformation.

Mentions: The flow cytometry results showed that in AVM patients, the double-positive cells (CD133 and CD34) and triple-positive cells (CD133, CD34, and KDR) accounted for 0.231%±0.179% and 0.051%±0.029% of total mononuclear cells in peripheral blood, significantly higher than 0.093%±0.045% and 0.023%±0.016% in healthy controls (Figure 2, P<0.05 in both comparisons). The level of SDF-1α was also elevated from 1,432±331.7 pg/mL in healthy control to 2,003.3±540.6 pg/mL in AVM patients (P<0.05). The number of EPCs and serum SDF-1α level showed a strong positive relationship (r=0.79, P<0.05). We also found double-positive EPCs (CD133/CD34) in AVM lesions (Figure 1D).


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)

EPCs from peripheral blood.Notes: This figure showed flow cytometry results of AVM patients (A); in controls (B). Left panels, raw images; middle panels, CD133+/CD34+ double-positive cells (upper right quadrant); and right panels, CD133+/CD34+/KDR+ triple-positive cells (upper right quadrant).Abbreviations: EPCs, endothelial progenitor cells; AVM, arteriovenous malformation.
© Copyright Policy
Related In: Results  -  Collection

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

f2-tcrm-11-1337: EPCs from peripheral blood.Notes: This figure showed flow cytometry results of AVM patients (A); in controls (B). Left panels, raw images; middle panels, CD133+/CD34+ double-positive cells (upper right quadrant); and right panels, CD133+/CD34+/KDR+ triple-positive cells (upper right quadrant).Abbreviations: EPCs, endothelial progenitor cells; AVM, arteriovenous malformation.
Mentions: The flow cytometry results showed that in AVM patients, the double-positive cells (CD133 and CD34) and triple-positive cells (CD133, CD34, and KDR) accounted for 0.231%±0.179% and 0.051%±0.029% of total mononuclear cells in peripheral blood, significantly higher than 0.093%±0.045% and 0.023%±0.016% in healthy controls (Figure 2, P<0.05 in both comparisons). The level of SDF-1α was also elevated from 1,432±331.7 pg/mL in healthy control to 2,003.3±540.6 pg/mL in AVM patients (P<0.05). The number of EPCs and serum SDF-1α level showed a strong positive relationship (r=0.79, P<0.05). We also found double-positive EPCs (CD133/CD34) in AVM lesions (Figure 1D).

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