title: Ionizing Radiation Impairs Endogenous Regeneration of Infarcted Heart: An In Vivo18F-FDG PET/CT and99mTc-Tetrofosmin SPECT/CT Study in Mice.
abstract: Epidemiological studies have suggested that ionizing radiation increases cardiovascular disease risk, but the relevant mechanism is poorly understood. We recently demonstrated that adult mice exposed to whole-body irradiation with 3 Gy gamma rays significantly decreases the number and quality of cardiac stem cells. To further determine if radiation impairs myocardial regenerative potency, a myocardial infarction model was established in adult C57BL/6 mice by ligating the left anterior descending artery approximately 6 h after sham- or whole-body gamma irradiation (0 or 3 Gy). To evaluate the regenerative potency of the infarcted heart, we measured the myocardial perfusion and remodeling by18F-FDG PET/CT and99mTc-tetrofosmin SPECT/CT at 1-2 days (baseline) and 14-15 days (end point) after infarction, respectively. Mice were sacrificed at day 15 after infarction, and heart tissue was collected for histological analysis. The infarct area of the left ventricle was significantly larger in irradiated mice than healthy controls 14 days after infarction, although it was similar between the groups at the baseline. However, histological analysis showed that the infarct size and left ventricle wall thickness were not significantly different among the groups. Compared to the healthy controls, irradiated mice had significantly less c-kit-positive stem cells, less Sca-1-positive stem cells, less proliferating cells, more apoptotic cells and lower vessel density within the infarcted heart. The results of this study suggest that whole-body irradiation with 3 Gy gamma rays impairs the endogenous regeneration of infarcted heart, which may indirectly predict future cardiovascular disease risk.
authors.affiliation: a   Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.affiliation: b   Department of Radioisotope Medicine, Atomic Bomb Disease Institute Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Kodai
authors.initials: K
authors.lastname: Nishi
authors.affiliation: a   Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Yoshishige
authors.initials: Y
authors.lastname: Urata
authors.affiliation: a   Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.affiliation: a   Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Al Shaimaa
authors.initials: AS
authors.lastname: Hasan
authors.affiliation: a   Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Goto
authors.affiliation: b   Department of Radioisotope Medicine, Atomic Bomb Disease Institute Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.affiliation: b   Department of Radioisotope Medicine, Atomic Bomb Disease Institute Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Zhao-Lan
authors.initials: ZL
authors.lastname: Li
authors.affiliation: a   Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D002452:Cell Count; D003331:Coronary Vessels / Q000473:pathology / Q000528:radiation effects; D019788:Fluorodeoxyglucose F18; D005720:Gamma Rays / Q000009:adverse effects; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology*; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D000072078:Positron Emission Tomography Computed Tomography; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012038:Regeneration / Q000528:radiation effects*; D000072098:Single Photon Emission Computed Tomography Computed Tomography; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D020257:Ventricular Remodeling / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D019788:Fluorodeoxyglucose F18; C078700:technetium tc-99m tetrofosmin; D019009:Proto-Oncogene Proteins c-kit