Atrial fibrillation is associated with cardiac hypoxia |
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| Authors: | Felix Gramley Johann Lorenzen Britta Jedamzik Kevin Gatter Eva Koellensperger Thomas Munzel Francesco Pezzella |
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| Institution: | 1. Department of Pharmacology, University of California Davis, School of Medicine, Davis, CA, USA;2. Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center and Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS, USA;1. Duke University Medical Center, Durham, NC;2. Duke Clinical Research Institute, Durham, NC;3. UCLA Division of Cardiology, Los Angeles, CA;4. New York University School of Medicine, Lenox Hill Hospital, New York, NY;5. Lankenau Institute for Medical Research, Wynnewood, PA;6. Stanford University School of Medicine, Stanford, CA;7. Mayo Clinic, Rochester, MN;8. Boston University School of Medicine, Boston, MA;9. Penn State University School of Medicine, Hershey, PA;10. Kaiser Permanente, Oakland, CA;11. Columbia University College of Physicians and Surgeons, New York, NY;12. Janssen Pharmaceuticals, Inc., Raritan, NJ;1. Division of Cardiology, Department of Medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael''s Hospital, University of Toronto, Canada;2. 2nd Academic Department of Cardiology, Attikon University Hospital, University of Athens Medical School, National and Kapodistrian University of Athens, Greece;1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China;2. Department of Cardiology, Central Hospital of Huangshi, Huangshi, China;3. Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, China;4. Department of clinical libratory, Renmin Hospital of Wuhan University, Wuhan, China |
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| Abstract: | BackgroundAtrial fibrillation (AF), the most common human arrhythmia, is responsible for substantial morbidity and mortality and may be promoted by selective atrial ischemia and atrial fibrosis. Consequently, we investigated markers for hypoxia and angiogenesis in AF.MethodsRight atrial appendages (n=158) were grouped according to heart rhythm sinus rhythm (SR) or AF]. The degree of fibrosis and microvessel density of all patients were determined morphometrically using Sirius-Red- and CD34/CD105-stained sections, respectively. Next, sections (n=77) underwent immunostaining to detect hypoxia- and angiogenesis-related proteins hypoxia-inducible factor (HIF)1α, HIF2α, vascular endothelial growth factor (VEGF), VEGF receptor 2 (KDR), phosphorylated KDR (pKDR), carboanhydrase IX, platelet-derived growth factor] and the apoptosis-related B-cell lymphoma 2 protein.ResultsFibrosis progressed significantly from 14.7±0.8% (SR) to 22.3±1.4% (AF). While the positive cytoplasmic staining of HIF1α, HIF2α, VEGF, KDR, and pKDR rose significantly from SR to AF, their nuclear fractions fell (only pKDR significantly). The median CD34/CD105-positive microvessel size increased significantly from SR to AF.ConclusionsAF is closely associated with an atrial up-regulation of hypoxic and angiogenic markers. Whether this is cause, effect, or co-phenomenon of fibrosis remains to be investigated. It is conceivable that fibrosis might lead to an increased O2 diffusion distance and thus induce ischemic signaling, which, in turn, leads to angiogenesis. |
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