| First Author | Saito T | Year | 2013 |
| Journal | Cardiovasc Res | Volume | 97 |
| Issue | 1 | Pages | 106-14 |
| PubMed ID | 23015640 | Mgi Jnum | J:210070 |
| Mgi Id | MGI:5569464 | Doi | 10.1093/cvr/cvs298 |
| Citation | Saito T, et al. (2013) Importance of endothelial NF-kappaB signalling in vascular remodelling and aortic aneurysm formation. Cardiovasc Res 97(1):106-14 |
| abstractText | AIMS: Vascular remodelling and aortic aneurysm formation are induced mainly by inflammatory responses in the adventitia and media. However, relatively little is known about the mechanistic significance of endothelium in the pathogenesis of these vascular disorders. The transcription factor nuclear factor-kappa B (NF-kappaB) regulates the expressions of numerous genes, including those related to pro-inflammatory responses. Therefore, to investigate the roles of endothelial pro-inflammatory responses, we examined the impact of blocking endothelial NF-kappaB signalling on intimal hyperplasia and aneurysm formation. METHODS AND RESULTS: To block endothelial NF-kappaB signalling, we used transgenic mice expressing dominant-negative IkappaBalpha selectively in endothelial cells (E-DNIkappaB mice). E-DNIkappaB mice were protected from the development of cuff injury-induced neointimal formation, in association with suppressed arterial expressions of cellular adhesion molecules, a macrophage marker, and inflammatory factors. In addition, the blockade of endothelial NF-kappaB signalling prevented abdominal aortic aneurysm formation in an experimental model, hypercholesterolaemic apolipoprotein E-deficient mice with angiotensin II infusion. In this aneurysm model as well, aortic expressions of an adhesion molecule, a macrophage marker, and inflammatory factors were suppressed with the inhibited expression and activity of matrix metalloproteinases in the aorta. CONCLUSION: Endothelial NF-kappaB activation up-regulates adhesion molecule expression, which may trigger macrophage infiltration and inflammation in the adventitia and media. Thus, the endothelium plays important roles in vascular remodelling and aneurysm formation through its intracellular NF-kappaB signalling. |
