Evaluation of Apoptosis with 99mTc-rhAnnexin V-128 and Inflammation with 18F-FDG in a Low-Dose Irradiation Model of Atherosclerosis in Apolipoprotein E-Deficient Mice.

Autor:	Kamkar M; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Canada., Wei L; Nordion, Inc., Kanata, Canada; and., Gaudet C; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Canada., Bugden M; Radiological Protection Research and Instrumentation Branch, Canadian Nuclear Laboratories, Chalk River, Canada., Petryk J; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Canada., Duan Y; Nordion, Inc., Kanata, Canada; and., Wyatt HM; Radiological Protection Research and Instrumentation Branch, Canadian Nuclear Laboratories, Chalk River, Canada., Wells RG; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Canada., Marcel YL; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Canada., Priest ND; Radiological Protection Research and Instrumentation Branch, Canadian Nuclear Laboratories, Chalk River, Canada., Mitchel RE; Radiological Protection Research and Instrumentation Branch, Canadian Nuclear Laboratories, Chalk River, Canada., Ruddy TD; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Canada truddy@ottawaheart.ca.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2016 Nov; Vol. 57 (11), pp. 1784-1791. Date of Electronic Publication: 2016 Jun 15.
DOI:	10.2967/jnumed.116.172346
Abstrakt:	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 18 F-FDG, and apoptosis with 99m Tc-rhAnnexin V-128 at 3 time points. Methods: ApoE -/- mice were fed a high-fat diet, exposed to low-dose 60 Co 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 18 F-FDG, 99m Tc-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 ( 18 F-FDG) and apoptosis ( 99m Tc-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 ( 18 F-FDG uptake) did not differ over time and did not correlate with average lesion stage. However, aortic arch apoptosis ( 99m Tc-rhAnnexin V-128) increased significantly by 4 mo and correlated with average lesion stage. There were no differences between the treatment subgroups ( 18 F-FDG, 99m Tc-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. (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)
Databáze:	MEDLINE
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