| First Author | Kröller-Schön S | Year | 2019 |
| Journal | Basic Res Cardiol | Volume | 114 |
| Issue | 2 | Pages | 8 |
| PubMed ID | 30643968 | Mgi Jnum | J:295076 |
| Mgi Id | MGI:6459618 | Doi | 10.1007/s00395-019-0717-2 |
| Citation | Kroller-Schon S, et al. (2019) Endothelial alpha1AMPK modulates angiotensin II-mediated vascular inflammation and dysfunction. Basic Res Cardiol 114(2):8 |
| abstractText | Mice with a global deletion of alpha1AMPK are characterized by endothelial dysfunction and NADPH oxidase subunit 2 (NOX-2)-mediated vascular oxidative stress. However, the underlying mechanisms are incompletely understood and may involve endothelial NOX-2 upregulation or facilitated vascular infiltration of phagocytic cells. Therefore, the current study was designed to investigate the vascular effects of chronic angiotensin II (AngII) infusion in mice with an endothelial-specific alpha1AMPK deletion. A mouse strain with endothelial-specific alpha1AMPK deletion was generated by breeding alpha1AMPK(flox/flox) mice with TekCre(+) or Cadh5Cre(+) mice. Chronic AngII infusion (0.5 mg/kg/day for 7day) caused mild endothelial dysfunction in wild-type mice that was significantly aggravated in endothelial alpha1AMPK knockout mice. Aortic NOX-2 and CD68 expression were increased, indicating that infiltrating leukocytes may significantly contribute to enhanced vascular oxidative stress. Flow cytometry revealed a higher abundance of aortic CD90.2(+) T-cells, CD11b(+)F4/80(+) macrophages and Ly6G(-)Ly6C(+) monocytes. Vascular mRNA expression of monocyte chemoattractant protein 1, CCL5 and vascular cell adhesion molecule 1 was enhanced in AngII-infused mice lacking endothelial alpha1AMPK, facilitating the recruitment of inflammatory cells to the vessel wall. In addition, AngII-induced upregulation of cytoprotective heme oxygenase 1 (HO-1) was blunted in mice with endothelial alpha1AMPK deletion, compatible with an impaired antioxidant defense in these animals. In summary, endothelial expressed alpha1AMPK limits the recruitment of inflammatory cells to the vessel wall and maintains HO-1 mediated antioxidant defense. Both mechanisms reduce vascular oxidative damage and preserve endothelial function during chronic AngII treatment. |
