ABSTRACT
Low-dose radiation in apolipoprotein E-deficient (ApoE-/-) mice has a protective effect with less subsequent atherosclerosis. Inflammation and apoptosis play major roles in the development of atherosclerosis. We evaluated the temporal pattern of the development of histologic atherosclerosis, inflammation with 18F-FDG, and apoptosis with 99mTc-rhAnnexin V-128 at 3 time points. METHODS: ApoE-/- mice were fed a high-fat diet, exposed to low-dose 60Co γ-radiation of 25 mGy at 2 mo of age, and evaluated within 1 wk (2-mo group), 1 mo (3-mo group), and 2 mo (4-mo group) from the time of radiation. Mice were divided into 3 subgroups and each received 18F-FDG, 99mTc-rhAnnexin V-128, or no radiotracer for autoradiography. Mice underwent euthanasia and aortic root dissection. The extent of atherosclerosis was determined by en face and Oil red O imaging. Aortic arch inflammation (18F-FDG) and apoptosis (99mTc-rhAnnexin V-128) were determined with digital autoradiography. Aortic sinus sections were stained with Sudan IV for assessment of lesion area and stage, antiCD68 antibody for inflammation and anti-cleaved-caspase 3 antibody for apoptosis. RESULTS: The extent of aortic atherosclerosis increased from 2 to 3 mo and from 3 to 4 mo. Inflammation (CD68) decreased and apoptosis (anti-cleaved-caspase 3 antibody) increased in aortic sinus slices measured as percentage of lesion by 4 mo. With increasing lesion stage, lesion inflammation decreased and lesion apoptosis increased. Aortic arch inflammation (18F-FDG uptake) did not differ over time and did not correlate with average lesion stage. However, aortic arch apoptosis (99mTc-rhAnnexin V-128) increased significantly by 4 mo and correlated with average lesion stage. There were no differences between the treatment subgroups (18F-FDG, 99mTc-rhAnnexin V-128, or no radiotracer). CONCLUSION: The temporal pattern of development of inflammation and apoptosis differ during the development of atherosclerosis in ApoE-/- mice treated with low-dose radiation. Advanced lesions are characterized by increased apoptosis and either less or similar amounts of inflammation, shown on immunohistochemistry and autoradiography. Treatment with radiotracers had no significant effects on extent of atherosclerosis, inflammation, or apoptosis.
Subject(s)
Annexin A5 , Apoptosis/radiation effects , Atherosclerosis/diagnostic imaging , Atherosclerosis/etiology , Organotechnetium Compounds , Vasculitis/diagnostic imaging , Vasculitis/etiology , Whole-Body Irradiation/adverse effects , Animals , Apolipoproteins E/genetics , Atherosclerosis/pathology , Dose-Response Relationship, Radiation , Female , Fluorodeoxyglucose F18 , Mice , Mice, Knockout , Radiopharmaceuticals , Vasculitis/pathologyABSTRACT
Helicobacter species can be found in a wide variety of animals and remain common contaminants of laboratory rodents. Fostering of neonatal pups has been used to eliminate Helicobacter spp. from various laboratory rodents, including laboratory mice and gerbils. Deer mice (Peromyscus maniculatus) from a captive colony enzootic for at least one Helicobacter species were mated, and the pups produced were fostered on laboratory mice 24 h after birth. After 2 rounds of fostering, both foster dams and pups were free of Helicobacter spp. as determined by fecal PCR analysis. Removal of Helicobacter infection through neonatal fostering has not been described previously for Peromyscus maniculatus.
