| First Author | Senchenkova EY | Year | 2018 |
| Journal | FASEB J | Volume | 32 |
| Issue | 6 | Pages | 3448-3456 |
| PubMed ID | 29452567 | Mgi Jnum | J:273840 |
| Mgi Id | MGI:6294600 | Doi | 10.1096/fj.201701068R |
| Citation | Senchenkova EY, et al. (2018) A critical role for both CD40 and VLA5 in angiotensin II-mediated thrombosis and inflammation. FASEB J 32(6):3448-3456 |
| abstractText | Angiotensin II (Ang-II)-induced hypertension is associated with accelerated thrombus formation in arterioles and leukocyte recruitment in venules. The mechanisms that underlie the prothrombotic and proinflammatory responses to chronic Ang-II administration remain poorly understood. We evaluated the role of CD40/CD40 ligand (CD40L) signaling in Ang-II-mediated microvascular responses and assessed whether and how soluble CD40L (sCD40L) contributes to this response. Intravital video microscopy was performed to analyze leukocyte recruitment and dihydrorhodamine-123 oxidation in postcapillary venules. Thrombus formation in cremaster muscle arterioles was induced by using the light/dye endothelial cell injury model. Wild-type (WT), CD40(-/-), and CD40L(-/-) mice received Ang-II for 14 d via osmotic minipumps. Some mice were treated with either recombinant sCD40L or the VLA5 (very late antigen 5; alpha5beta1) antagonist, ATN-161. Our results demonstrate that CD40(-/-), CD40L(-/-), and WT mice that were treated with ATN-161 were protected against the thrombotic and inflammatory effects of Ang-II infusion. Infusion of sCD40L into CD40(-/-) or CD40L(-/-) mice restored the prothrombotic effect of Ang-II infusion. Mice that were treated with ATN-161 and infused with sCD40L were protected against accelerated thrombosis. Collectively, these novel findings suggest that the mechanisms that underlie Ang-II-dependent thrombotic and inflammatory responses link to the signaling of CD40L via both CD40 and VLA5.-Senchenkova, E. Y., Russell, J., Vital, S. A., Yildirim, A., Orr, A. W., Granger, D. N., Gavins, F. N. E. A critical role for both CD40 and VLA5 in angiotensin II-mediated thrombosis and inflammation. |
