| First Author | Tirziu D | Year | 2012 |
| Journal | Circulation | Volume | 126 |
| Issue | 22 | Pages | 2589-600 |
| PubMed ID | 23091063 | Mgi Jnum | J:210148 |
| Mgi Id | MGI:5569609 | Doi | 10.1161/CIRCULATIONAHA.112.119321 |
| Citation | Tirziu D, et al. (2012) Endothelial nuclear factor-kappaB-dependent regulation of arteriogenesis and branching. Circulation 126(22):2589-600 |
| abstractText | BACKGROUND: Arteriogenesis and collateral formation are complex processes requiring integration of multiple inputs to coordinate vessel branching, growth, maturation, and network size. Factors regulating these processes have not been determined. METHODS AND RESULTS: We used an inhibitor of NFkappaB activation (IkappaBalphaSR) under control of an endothelial-specific inducible promoter to selectively suppress endothelial nuclear factor-kappaB activation during development, in the adult vasculature, or in vitro. Inhibition of nuclear factor-kappaB activation resulted in formation of an excessively branched arterial network that was composed of immature vessels and provided poor distal tissue perfusion. Molecular analysis demonstrated reduced adhesion molecule expression leading to decreased monocyte influx, reduced hypoxia-inducible factor-1alpha levels, and a marked decrease in delta-like ligand 4 expression with a consequent decrease in Notch signaling. The latter was the principal cause of increased vascular branching as treatment with Jagged-1 peptide reduced the size of the arterial network to baseline levels. CONCLUSIONS: These findings identify nuclear factor-kappaB as a key regulator of adult and developmental arteriogenesis and collateral formation. Nuclear factor-kappaB achieves this by regulating hypoxia-inducible factor-1alpha-dependent expression of vascular endothelial growth factor-A and platelet-derived growth factor-BB, which are necessary for the development and maturation of the arterial collateral network, and by regulating delta-like ligand 4 expression, which in turn determines the size and complexity of the network. |
