MicroRNA-155 Exerts Cell-Specific Antiangiogenic but Proarteriogenic Effects During Adaptive Neovascularization. Issue 18 (5th May 2015)

• Record Type: Journal Article
• Authors: Pankratz, Franziska; Bemtgen, Xavier; Zeiser, Robert; Leonhardt, Franziska; Kreuzaler, Sheena; Hilgendorf, Ingo; Smolka, Christian; Helbing, Thomas; Hoefer, Imo; Esser, Jennifer S.; Kustermann, Max; Moser, Martin; Bode, Christoph; Grundmann, Sebastian
• Is Part Of: Circulation. Volume 131:Issue 18(2015)
• Publication Date: 2015-05-05
• Subjects: Blood -- Circulation -- Periodicals; Cardiovascular system -- Periodicals; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; 616.1
• DOI: 10.1161/CIRCULATIONAHA.114.014579
• Languages: English
• ISSNs: 0009-7322

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background—</title> <p>Adaptive neovascularization after arterial occlusion is an important compensatory mechanism in cardiovascular disease and includes both the remodeling of pre-existing vessels to collateral arteries (arteriogenesis) and angiogenic capillary growth. We now aimed to identify regulatory microRNAs involved in the modulation of neovascularization after femoral artery occlusion in mice.</p> </sec> <sec> <title>Methods and Results—</title> <p>Using microRNA-transcriptome analysis, we identified miR-155 as a downregulated microRNA during hindlimb ischemia. Correspondingly, inhibition of miR-155 in endothelial cells had a stimulatory effect on proliferation and angiogenic tube formation via derepression of its direct target gene angiotensin II type 1 receptor. Surprisingly, miR-155–deficient mice showed an unexpected phenotype in vivo, with a strong reduction of blood flow recovery after femoral artery ligation (arteriogenesis) dependent on the attenuation of leukocyte-endothelial interaction and a reduction of proarteriogenic cytokine expression. Consistently, miR-155–deficient macrophages exhibit a specific alteration of the proarteriogenic cytokine expression profile, which is partly mediated by the direct miR-155 target gene SOCS-1.</p> </sec> <sec> <title>Conclusions—</title> <p>Our data demonstrate that miR-155 exerts an antiangiogenic but proarteriogenic function in the regulation of neovascularization via the suppression of divergent cell-specific target genes and that its expression in both endothelial and bone marrow–derived cells is essential for arteriogenesis in response to hindlimb ischemia in mice.</p> </sec> </abstract>