| First Author | Schuhmacher S | Year | 2011 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 31 |
| Issue | 3 | Pages | 560-6 |
| PubMed ID | 21205985 | Mgi Jnum | J:184176 |
| Mgi Id | MGI:5320388 | Doi | 10.1161/ATVBAHA.110.219543 |
| Citation | Schuhmacher S, et al. (2011) alpha1AMP-activated protein kinase preserves endothelial function during chronic angiotensin II treatment by limiting Nox2 upregulation. Arterioscler Thromb Vasc Biol 31(3):560-6 |
| abstractText | OBJECTIVE: Besides its well-described metabolic effects, vascular AMP-activated protein kinase (AMPK) can activate endothelial NO synthase, promotes angiogenesis, and limits endothelial cell apoptosis. The current study was designed to study the effects of alpha1AMPK deletion during vascular disease in vivo. METHODS AND RESULTS: Chronic angiotensin II infusion at low subpressor doses caused a mild endothelial dysfunction that was significantly aggravated in alpha1AMPK-knockout mice. Unexpectedly, this endothelial dysfunction was not associated with decreased NO content, because NO levels measured by serum nitrite or electron paramagnetic resonance were even increased. However, because of parallel superoxide production, NO was consumed under production of peroxynitrite in angiotensin II-treated alpha1AMPK-knockout mice, associated with NADPH oxidase activation and Nox2 upregulation. As Nox2 is also a component of phagocyte NADPH oxidases, we found a vascular upregulation of several proinflammatory markers, including inducible NO synthase, vascular cell adhesion molecule-1, and cyclooxygenase-2. Cotreatment with the NADPH oxidase inhibitor apocynin was able to prevent vascular inflammation and also partially restored endothelial function in alpha1AMPK-knockout mice. CONCLUSIONS: Our data indicate that in vivo alpha1AMPK deletion leads to Nox2 upregulation, resulting in endothelial dysfunction and vascular inflammation. This implicates basal AMPK activity as a protective, redox-regulating element in vascular homeostasis. |
