| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Steven, Sebastian Münzel, Thomas Mikhed, Yuliya Widder, Julian Schönfelder, Tanja Daiber, Andreas Hu, Hanhan Knorr, Maike Brähler, Melanie Wenzel, Philip Oelze, Matthias Kossmann, Sabine Bauersachs, Johann Fraccarollo, Daniela Becker, Christian Brandt, Moritz Karbach, Susanne H. |
| Description |
Author Affiliation: Kossmann S ( From the 2nd Medical Clinic, Center for Thrombosis and Hemostasis, and.); Hu H ( Center for Thrombosis and Hemostasis, and.); Steven S ( From the 2nd Medical Clinic, Center for Thrombosis and Hemostasis, and.); Schönfelder T ( Center for Thrombosis and Hemostasis, and.); Fraccarollo D ( the Clinic for Cardiology and Angiology, Hannover School of Medicine, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany, and.); Mikhed Y ( From the 2nd Medical Clinic.); Brähler M ( Center for Thrombosis and Hemostasis, and Department of Dermatology, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.); Knorr M ( From the 2nd Medical Clinic, Center for Thrombosis and Hemostasis, and.); Brandt M ( Center for Thrombosis and Hemostasis, and the Stanford School of Medicine, Stanford, California 94305.); Karbach SH ( From the 2nd Medical Clinic.); Becker C ( Center for Thrombosis and Hemostasis, and Department of Dermatology, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.); Oelze M ( From the 2nd Medical Clinic.); Bauersachs J ( the Clinic for Cardiology and Angiology, Hannover School of Medicine, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany, and.); Widder J ( the Clinic for Cardiology and Angiology, Hannover School of Medicine, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany, and.); Münzel T ( From the 2nd Medical Clinic.); Daiber A ( From the 2nd Medical Clinic.); Wenzel P ( From the 2nd Medical Clinic, Center for Thrombosis and Hemostasis, and wenzelp@uni-mainz.de.) |
| Abstract |
Endothelial nitric-oxide synthase (eNOS) uncoupling and increased inducible NOS (iNOS) activity amplify vascular oxidative stress. The role of inflammatory myelomonocytic cells as mediators of these processes and their impact on tetrahydrobiopterin availability and function have not yet been defined. Angiotensin II (ATII, 1 mg/kg/day for 7 days) increased Ly6C(high) and CD11b(+)/iNOS(high) leukocytes and up-regulated levels of eNOS glutathionylation in aortas of C57BL/6 mice. Vascular iNOS-dependent NO formation was increased, whereas eNOS-dependent NO formation was decreased in aortas of ATII-infused mice as assessed by electron paramagnetic resonance (EPR) spectroscopy. Diphtheria toxin-mediated ablation of lysozyme M-positive (LysM(+)) monocytes in ATII-infused LysM(iDTR) transgenic mice prevented eNOS glutathionylation and eNOS-derived N(ω)-nitro-L-arginine methyl ester-sensitive superoxide formation in the endothelial layer. ATII increased vascular guanosine triphosphate cyclohydrolase I expression and biopterin synthesis in parallel, which was reduced in monocyte-depleted LysM(iDTR) mice. Vascular tetrahydrobiopterin was increased by ATII infusion but was even higher in monocyte-depleted ATII-infused mice, which was paralleled by a strong up-regulation of dihydrofolate reductase expression. EPR spectroscopy revealed that both vascular iNOS- and eNOS-dependent NO formation were normalized in ATII-infused mice following monocyte depletion. Additionally, deletion as well as pharmacologic inhibition of iNOS prevented ATII-induced endothelial dysfunction. In summary, ATII induces an inflammatory cell-dependent increase of iNOS, guanosine triphosphate cyclohydrolase I, tetrahydrobiopterin, NO formation, and nitro-oxidative stress as well as eNOS uncoupling in the vessel wall, which can be prevented by ablation of LysM(+) monocytes. |
| ISSN |
00219258 |
| e-ISSN |
1083351X |
| Journal |
Journal of Biological Chemistry |
| Issue Number |
40 |
| Volume Number |
289 |
| Language |
English |
| Publisher |
American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date |
2014-10-03 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Angiotensin II Immunology Monocytes Enzymology Nitric Oxide Synthase Type III Oxidative Stress Genetics Animals Biopterin Analogs & Derivatives Endothelium, Vascular Mice Mice, Inbred C57BL Mice, Knockout Nitric Oxide Nitric Oxide Synthase Type II Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Biochemistry Molecular Biology |
