| The renin inhibitor aliskiren upregulates pro-angiogenic cells and reduces atherogenesis in mice. | |
MedLine Citation:
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PMID: 20857126 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Sca-1 and VEGFR-2 positive pro-angiogenic cells (PAC) predict outcome of patients with vascular disease. Activation of the renin-angiotensin-aldosterone system impairs PAC function. The effects of the direct renin inhibitor aliskiren on PAC numbers and function are not known. Treatment of C57Bl/6 mice and Apo E(-/-) mice on high-cholesterol diet with aliskiren, 25 mg/kg/day s.c. for 3-6 weeks, reduced systolic and diastolic blood pressure by -11.5 and -13.7% compared to vehicle. Aliskiren increased Sca-1/VEGFR-2 positive PAC in the blood (159 ± 14%) and spleen-derived DiLDL/lectin positive PAC (180 ± 21%). Migratory capacity of PAC was increased to 165 ± 16%. In cultured human PAC, aliskiren dose-dependently increased the number of colony forming units to 152 ± 9% (1 μmol/l) and 187 ± 7% (10 μmol/l), which was prevented by the eNOS inhibitor LNMA. H₂O₂-induced apoptosis of cultured human PAC was reduced to 77 ± 23%. In Apo E(-/-) mice, aliskiren reduced atherosclerotic plaque area in the aortic sinus by 58 ± 4%. Circulating Sca-1/VEGFR-2 positive PAC were upregulated to 180 ± 25% and migratory capacity of PAC was increased to 127 ± 7%. Aliskiren reduced vascular NADPH oxidase activity to 41.6 ± 6.7%. Despite similar blood pressure lowering, treatment with hydralazine (25 mg/kg/day) did not significantly influence atherogenesis or PAC. Treatment of C57Bl/6 mice with a lower dose of aliskiren (15 mg/kg/day) did not affect blood pressure but increased cultured DiLDL/lectin positive PAC to 229 ± 30% and their migratory capacity to 214 ± 24%. Aliskiren increased number and function of PAC in mice and prevented atherosclerotic lesion formation. The effects were observed independent of blood pressure lowering. |
Authors:
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Janine Pöss; Christian Werner; Dominik Lorenz; Christoph Gensch; Michael Böhm; Ulrich Laufs |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-21 |
Journal Detail:
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Title: Basic research in cardiology Volume: 105 ISSN: 1435-1803 ISO Abbreviation: Basic Res. Cardiol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0360342 Medline TA: Basic Res Cardiol Country: Germany |
Other Details:
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Languages: eng Pagination: 725-35 Citation Subset: IM |
Affiliation:
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Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Kirrbergerstr., 66421, Homburg, Saar, Germany. Janine.poess@gmx.de |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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