Dose-dependent effect of radiation on angiogenic and angiostatic CXC chemokine expression in human endothelial cells |
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| Institution: | 1. Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN;2. Department of Medicine, Multidisciplinary Epidemiology and Translational Research in Intensive Care, Emergency and Perioperative Medicine (METRIC), Mayo Clinic, Rochester, MN;3. Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN;4. Department of Neurology, Division of Critical Care Neurology, Mayo Clinic, Rochester, MN;1. Unidad de Cuidados Intensivos, Hospital Universitario SAS de Jerez, C/ Circunvalación s/n, 11408 Jerez de la Frontera, Spain;2. Unidad de Gestión Clínica de Cardiología, Hospital Universitario SAS de Jerez, C/ Circunvalación s/n, 11408 Jerez de la Frontera, Spain;3. Department of Anesthesia and Critical Care, St Georges University Hospitals NHS Trust, Blackshaw Road, SW17 0QT London, UK;1. Department of Electrocardiology, The John Paul II Hospital, Kraków, Poland;2. Department of Cardiology, Klodzko County Hospital, Kłodzko, Poland;3. Department of Cardiology, Wroclaw Medical University, Wroclaw, Poland;4. Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland;1. Guy''s and St Thomas'' Hospital, UK;2. King''s College London, UK |
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| Abstract: | Blood vessel growth is regulated by angiogenic and angiostatic CXC chemokines, and radiation is a vasculogenic stimulus. We investigated the effect of radiation on endothelial cell chemokine signaling, receptor expression, and migration and apoptosis. Human umbilical vein endothelial cells were exposed to a single fraction of 0, 5, or 20 Gy of ionizing radiation (IR). All vasculogenic chemokines (CXCL1–3/5–8) increased 3–13-fold after 5 or 20 Gy IR. 20 Gy induced a marked increase (1.6–4-fold) in angiostatic CXC chemokines. CXCR4 expression increased 3.5 and 7-fold at 48 h after 5 and 20 Gy, respectively. Bone marrow progenitor cell chemotaxis was augmented by conditioned media from cells treated with 5 Gy IR. Whereas 5 Gy markedly decreased intrinsic cell apoptosis (0 Gy = 16% ± 3.6 vs. 5 Gy = 4.5% ± 0.3), 20 Gy increased it (21.4% ± 1.2); a reflection of pro-survival angiogenic chemokine expression. Radiation induces a dose-dependent increase in pro-angiogenic CXC chemokines and CXCR4. In contrast, angiostatic chemokines and apoptosis were induced at higher (20 Gy) radiation doses. Cell migration improved significantly following 5 Gy, but not 20 Gy IR. Collectively, these data suggest that lower doses of IR induce an angiogenic cascade while higher doses produce an angiostatic profile. |
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