| First Author | Ashina K | Year | 2015 |
| Journal | Biochem Biophys Res Commun | Volume | 464 |
| Issue | 2 | Pages | 590-5 |
| PubMed ID | 26163262 | Mgi Jnum | J:228764 |
| Mgi Id | MGI:5708803 | Doi | 10.1016/j.bbrc.2015.07.014 |
| Citation | Ashina K, et al. (2015) VEGF-induced blood flow increase causes vascular hyper-permeability in vivo. Biochem Biophys Res Commun 464(2):590-5 |
| abstractText | VEGF is known to cause vascular leak, its detailed mechanisms in vivo remain unclear. Here, we investigated the mechanisms underlying VEGF-induced vascular hyper-permeability focusing on two major regulators of vascular permeability: blood flow and endothelial barrier function. Administration of VEGF caused vascular hyper-permeability and tissue swelling in mouse ears, which were abolished by VEGF receptor-2 blockade. Intravital imaging showed that VEGF dilated ear arteries but not veins, and laser Doppler velocimetry showed that VEGF quickly increased tissue blood flow along with arterial dilation. Whole-mount immunostaining showed that VEGF phosphorylated endothelial nitric oxide synthase (eNOS) at residue Ser1177 and disrupted the alignment of vascular endothelial-cadherin (VE-cadherin) around the endothelial cell borders in mouse ear skin, indicating endothelial nitric oxide (NO) production and barrier disruption. Administration of the nitric oxide synthesis inhibitor, L-NAME, as well as the vasoconstrictor phenylephrine, abolished all VEGF-induced responses, including blood flow increase, dye leakage, and tissue swelling. However, these two treatments did not alter the intracellular localization of VE-cadherin-induced by VEGF. These observations underscore the importance of vascular dilation and, subsequent increase in blood flow, as well as, endothelial barrier disruption in the mechanisms of VEGF-induced vascular hyper-permeability. |
