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Vascular endothelial growth factor receptor and coreceptor expression in human acute respiratory distress syndrome.

Medford AR, Ibrahim NB, Millar AB - J Crit Care (2008)

Bottom Line: Vascular endothelial growth factor receptors and coreceptors regulate this bioactivity.We hypothesized VEGF receptors 1 and 2 (VEGFR1, VEGFR2) and coreceptor neuropilin-1 (NRP-1) would be expressed in human lung tissue with a significant change in expression in ARDS lung.The mechanisms behind these observations remain to be clarified.

View Article: PubMed Central - PubMed

Affiliation: Lung Research Group, Department of Clinical Science at North Bristol, University of Bristol, Southmead Hospital, Westbury-on-Trym, Bristol, United Kingdom.

ABSTRACT

Background: Acute respiratory distress syndrome (ARDS) is characterized by the development of noncardiogenic pulmonary edema, which has been related to the bioactivity of vascular endothelial growth factor (VEGF). Vascular endothelial growth factor receptors and coreceptors regulate this bioactivity. We hypothesized VEGF receptors 1 and 2 (VEGFR1, VEGFR2) and coreceptor neuropilin-1 (NRP-1) would be expressed in human lung tissue with a significant change in expression in ARDS lung.

Methods: Archival "normal" (no lung pathology and non-ARDS), "early" (within 48 hours), and "later" (after day 7) ARDS lung-tissue sections (n = 5) were immunostained for VEGFR1, VEGFR2, and NRP-1 from human subjects (n = 4). Staining was assessed densitometrically using Histometrix software.

Results: VEGFR1, VEGFR2, and NRP-1 were expressed on both sides of the alveolar-capillary membrane in both normal and ARDS human lung tissue. In later ARDS, there was a significant up-regulation of VEGFR1 and VEGFR2 versus normal and early ARDS (P < .0001). Neuropilin-1 was down-regulated in early ARDS versus normal lung (P < .05), with normalization in later ARDS (P < .001).

Conclusion: Differential temporal VEGFR1, VEGFR2, and NRP-1 up-regulation occurs in human ARDS, providing evidence of further functional regulation of VEGF bioactivity via VEGFR2 consistent with a protective role for VEGF in lung injury recovery. The mechanisms behind these observations remain to be clarified.

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A–C, Graphs of quantitative immunostaining densities (plotted as pixels of staining per unit area) for VEGFR1 (A), VEGFR2 (B), and NRP-1 (C) in each disease state. All data are normally distributed and plotted as mean and standard error. A–B, P < .001 (Bonferroni) for normal versus late and early versus late (highlighted*); otherwise, other comparisons are not significant. C, P < .001 (Bonferroni) for early versus late (highlighted*); P < .05 (Bonferroni) for normal versus early (highlighted†); otherwise, other comparisons are not significant.
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fig5: A–C, Graphs of quantitative immunostaining densities (plotted as pixels of staining per unit area) for VEGFR1 (A), VEGFR2 (B), and NRP-1 (C) in each disease state. All data are normally distributed and plotted as mean and standard error. A–B, P < .001 (Bonferroni) for normal versus late and early versus late (highlighted*); otherwise, other comparisons are not significant. C, P < .001 (Bonferroni) for early versus late (highlighted*); P < .05 (Bonferroni) for normal versus early (highlighted†); otherwise, other comparisons are not significant.

Mentions: Histometrix densitometric analysis supported the visual observations noticed in immunostaining and is presented graphically in Fig. 5A–C. Differential time-dependent changes in VEGFR1, VEGFR2, and NRP-1 expression were noted. Vascular endothelial growth factor receptors 1 and 2 expression was significantly up-regulated in the later stages of ARDS (P < .001, Bonferroni) versus normal and early ARDS lung (Fig. 5A–B).


Vascular endothelial growth factor receptor and coreceptor expression in human acute respiratory distress syndrome.

Medford AR, Ibrahim NB, Millar AB - J Crit Care (2008)

A–C, Graphs of quantitative immunostaining densities (plotted as pixels of staining per unit area) for VEGFR1 (A), VEGFR2 (B), and NRP-1 (C) in each disease state. All data are normally distributed and plotted as mean and standard error. A–B, P < .001 (Bonferroni) for normal versus late and early versus late (highlighted*); otherwise, other comparisons are not significant. C, P < .001 (Bonferroni) for early versus late (highlighted*); P < .05 (Bonferroni) for normal versus early (highlighted†); otherwise, other comparisons are not significant.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2698064&req=5

fig5: A–C, Graphs of quantitative immunostaining densities (plotted as pixels of staining per unit area) for VEGFR1 (A), VEGFR2 (B), and NRP-1 (C) in each disease state. All data are normally distributed and plotted as mean and standard error. A–B, P < .001 (Bonferroni) for normal versus late and early versus late (highlighted*); otherwise, other comparisons are not significant. C, P < .001 (Bonferroni) for early versus late (highlighted*); P < .05 (Bonferroni) for normal versus early (highlighted†); otherwise, other comparisons are not significant.
Mentions: Histometrix densitometric analysis supported the visual observations noticed in immunostaining and is presented graphically in Fig. 5A–C. Differential time-dependent changes in VEGFR1, VEGFR2, and NRP-1 expression were noted. Vascular endothelial growth factor receptors 1 and 2 expression was significantly up-regulated in the later stages of ARDS (P < .001, Bonferroni) versus normal and early ARDS lung (Fig. 5A–B).

Bottom Line: Vascular endothelial growth factor receptors and coreceptors regulate this bioactivity.We hypothesized VEGF receptors 1 and 2 (VEGFR1, VEGFR2) and coreceptor neuropilin-1 (NRP-1) would be expressed in human lung tissue with a significant change in expression in ARDS lung.The mechanisms behind these observations remain to be clarified.

View Article: PubMed Central - PubMed

Affiliation: Lung Research Group, Department of Clinical Science at North Bristol, University of Bristol, Southmead Hospital, Westbury-on-Trym, Bristol, United Kingdom.

ABSTRACT

Background: Acute respiratory distress syndrome (ARDS) is characterized by the development of noncardiogenic pulmonary edema, which has been related to the bioactivity of vascular endothelial growth factor (VEGF). Vascular endothelial growth factor receptors and coreceptors regulate this bioactivity. We hypothesized VEGF receptors 1 and 2 (VEGFR1, VEGFR2) and coreceptor neuropilin-1 (NRP-1) would be expressed in human lung tissue with a significant change in expression in ARDS lung.

Methods: Archival "normal" (no lung pathology and non-ARDS), "early" (within 48 hours), and "later" (after day 7) ARDS lung-tissue sections (n = 5) were immunostained for VEGFR1, VEGFR2, and NRP-1 from human subjects (n = 4). Staining was assessed densitometrically using Histometrix software.

Results: VEGFR1, VEGFR2, and NRP-1 were expressed on both sides of the alveolar-capillary membrane in both normal and ARDS human lung tissue. In later ARDS, there was a significant up-regulation of VEGFR1 and VEGFR2 versus normal and early ARDS (P < .0001). Neuropilin-1 was down-regulated in early ARDS versus normal lung (P < .05), with normalization in later ARDS (P < .001).

Conclusion: Differential temporal VEGFR1, VEGFR2, and NRP-1 up-regulation occurs in human ARDS, providing evidence of further functional regulation of VEGF bioactivity via VEGFR2 consistent with a protective role for VEGF in lung injury recovery. The mechanisms behind these observations remain to be clarified.

Show MeSH
Related in: MedlinePlus