Lysozyme M-positive monocytes mediate angiotensin II-induced arterial hypertension and vascular dysfunction.
Abstract | BACKGROUND: METHODS AND RESULTS:
Angiotensin II (1 mg · kg(-1) · d(-1) for 7 days) increased the number of both CD11b(+)Gr-1(low)F4/80(+) macrophages and CD11b(+)Gr-1(high)F4/80(-) neutrophils in mouse aorta (verified by flow cytometry). Selective ablation of lysozyme M-positive (LysM(+)) myelomonocytic cells by low-dose diphtheria toxin in mice with inducible expression of the diphtheria toxin receptor (LysM(iDTR) mice) reduced the number of monocytes in the circulation and limited ATII-induced infiltration of these cells into the vascular wall, whereas the number of neutrophils was not reduced. Depletion of LysM(+) cells attenuated ATII-induced blood pressure increase (measured by radiotelemetry) and vascular endothelial and smooth muscle dysfunction (assessed by aortic ring relaxation studies) and reduced vascular superoxide formation (measured by chemiluminescence, cytochrome c assay, and oxidative fluorescence microtopography) and the expression of NADPH oxidase subunits gp91( phox) and p67( phox) (assessed by Western blot and mRNA reverse-transcription polymerase chain reaction). Adoptive transfer of wild-type CD11b(+)Gr-1(+) monocytes into depleted LysM(iDTR) mice reestablished ATII-induced vascular dysfunction, oxidative stress, and arterial hypertension, whereas transfer of CD11b(+)Gr-1(+) neutrophils or monocytes from gp91( phox) or ATII receptor type 1 knockout mice did not. CONCLUSIONS- Infiltrating monocytes with a proinflammatory phenotype and macrophages rather than neutrophils appear to be essential for ATII-induced vascular dysfunction and arterial hypertension.
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Authors | Philip Wenzel, Maike Knorr, Sabine Kossmann, Jan Stratmann, Michael Hausding, Swenja Schuhmacher, Susanne H Karbach, Melanie Schwenk, Nir Yogev, Eberhard Schulz, Matthias Oelze, Stephan Grabbe, Helmut Jonuleit, Christian Becker, Andreas Daiber, Ari Waisman, Thomas Münzel |
Journal | Circulation
(Circulation)
Vol. 124
Issue 12
Pg. 1370-81
(Sep 20 2011)
ISSN: 1524-4539 [Electronic] United States |
PMID | 21875910
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CD11b Antigen
- Gr-1 protein, mouse
- Reactive Oxygen Species
- Receptors, Chemokine
- Vasoconstrictor Agents
- Angiotensin II
- Nitric Oxide
- Muramidase
- lysozyme M, mouse
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Topics |
- Angiotensin II
(pharmacology)
- Animals
- CD11b Antigen
(metabolism)
- Endothelium, Vascular
(immunology, metabolism)
- Gene Expression
(immunology)
- Hypertension
(chemically induced, immunology, metabolism)
- Macrophages
(immunology, metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Monocytes
(immunology, metabolism)
- Muramidase
(genetics, immunology, metabolism)
- Muscle, Smooth, Vascular
(immunology, metabolism)
- Neutrophils
(immunology, metabolism)
- Nitric Oxide
(metabolism)
- Oxidative Stress
(physiology)
- Reactive Oxygen Species
(metabolism)
- Receptors, Chemokine
(metabolism)
- Respiratory Burst
(physiology)
- Vasculitis
(chemically induced, immunology, metabolism)
- Vasoconstrictor Agents
(pharmacology)
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