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Angiopoietin-1 and vascular endothelial growth factor regulation of leukocyte adhesion to endothelial cells: role of nuclear receptor-77.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Ismail, Hodan Ahmed Mofarrahi, Mahroo EchavarrÃa, R. Mauricio Harel, Sharon Verdin, Eric Lim, Hyung Woo Jin, Zheng-gen Sun, Jianxin Zeng, Huiyan Hussain, Sabah N. A. |
| Copyright Year | 2012 |
| Abstract | OBJECTIVE Vascular endothelial growth factor (VEGF) promotes leukocyte adhesion to endothelial cells (ECs). Angiopoietin-1 (Ang-1) inhibits this response. Nuclear receptor-77 (Nur77) is a proangiogenic nuclear receptor. In the present study, we assessed the influence of Ang-1 and VEGF on Nur77 expression in ECs, and evaluated its role in Ang-1/VEGF-mediated leukocyte adhesion. METHODS AND RESULTS Expression of Nur77 was evaluated with real-time polymerase chain reaction and immunoblotting. Adhesion of leukocytes to ECs was monitored with inverted microscopy. Nur77 expression or activity was inhibited using adenoviruses expressing dominant-negative form of Nur77, retroviruses expressing Nur77 in the antisense direction, and small interfering RNA oligos. Both Ang-1 and VEGF induce Nur77 expression, by >5- and 30-fold, respectively. When combined, Ang-1 potentiates VEGF-induced Nur77 expression. Ang-1 induces Nur77 through the phosphoinositide 3-kinase and extracellular signal-regulated protein kinase 1/2 pathways. VEGF induces Nur77 expression through the protein kinase D/histone deacetylase 7/myocyte enhancer factor 2 and extracellular signal-regulated protein kinase 1/2 pathways. VEGF induces nuclear factor-kappaB transcription factor, vascular cell adhesion molecule-1, and E-selectin expressions, and promotes leukocyte adhesion to ECs. Ang-1 inhibits these responses. This inhibitory effect of Ang-1 disappears when Nur77 expression is disrupted, restoring the inductive effects of VEGF on adhesion molecule expression, and increased leukocyte adhesion to ECs. CONCLUSIONS Nur77 promotes anti-inflammatory effects of Ang-1, and functions as a negative feedback inhibitor of VEGF-induced EC activation. |
| Starting Page | 188 |
| Ending Page | 190 |
| Page Count | 3 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/32/7/1707.full.pdf |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/32/7/1707.full.pdf?download=true |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/early/2012/05/24/ATVBAHA.112.251546.full.pdf |
| PubMed reference number | 22628435v1 |
| Alternate Webpage(s) | https://doi.org/10.1161/ATVBAHA.112.251546 |
| DOI | 10.1161/ATVBAHA.112.251546 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Volume Number | 32 |
| Issue Number | 7 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 2',5'-oligoadenylate ANGPT1 protein, human Adenoviruses Anti-Inflammatory Agents Cell Adhesion Molecules E-Selectin Endothelial Cells Endothelial Growth Factors Enhancer of transcription Growth Factor Histone Deacetylase Histones Immunoblotting Leukemia, B-Cell Leukocytes Nuclear Receptor Subfamily 4, Group A, Member 1 Phosphatidylinositols Polymerase Chain Reaction Protein Kinases RNA Receptors, Nuclear Retroviridae Selectins antisense therapy leukocyte cell-cell adhesion |
| Content Type | Text |
| Resource Type | Article |
