Abstract 15492: Imaging Oxidative Stress in Unstable Atherosclerotic Plaque With Iodine-125-Labeled 4-Hydroxy-2-Nonenal in vivo
Introduction: Oxidative stress contributes to the progress of atherosclerosis as inflammation, serum lipid overload, and aging do. The early identification of unstable atherosclerotic plaque, which consists of vulnerable capsule, inflammatory cells, and high fat contents, is a key for prevention from stroke or acute coronary event, but has been still an unsolved issue.
Hypothesis: We assessed the hypothesis that iodine-125-labeled anti-4-hydroxy-2-nonenal antibody (I-125-4HNE-Ab) could visualize oxidative stress in the unstable stage of atherosclerotic plaque in vivo.
Methods: We prepared Anti-4HNE antibody radio-labeled with iodine-125 by chloramine-T method. Three hours after the injection of I-125-4HNE-Ab into the spontaneously hyperlipidemic C57BL/6.KOR-Apoeshl, apolipoprotein E gene knockout mice (ApoE-KO) and C57BL/6 mice as control fed with normal chow for 16weeks, serum lipid profile were evaluated and the aortas were removed. Then they were subjected to scintillation counting of radioactivity and autoradiography as well as histological assessment, including en face staining with Oil Red and immunohistochemical staining for 8-hydroxy-2-deoxyguanosine (8-OHdG).
Results: KOR-Apoeshl and ApoE-KO exhibited hyperlipidemia and their aorta had intima-media thickness vulnerable capsule, inflammmatory cells as well as high fat contents, which was consistent with the features of unstable atherosclerotic plaques. Immunohistochemical staining for 8-OHdG indicated that oxidative stress was existed in these plaques. Scintillation counting of radioactivity revealed the increase of tracer uptakes in KOR-Apoeshl and ApoE-KO (p<0.01, p<0.01 vs control, respectively). Notably, the tracer accumulation areas detected by autoradiography were predominant in ascending aorta and aortic arch, which was demonstrated to be closely correlated with unstable atherosclerotic plaques.
Conclusions: In conclusion, I-125-4HNE-Ab can visualize unstable atherosclerotic plaque by detecting oxidative stress in mice with hyperlipidemia. This method can provide a feasible strategy to develop a new method for tissue characterization in atherosclerotic plaques as well as determining a high risk group of stroke or acute coronary syndrome.
- © 2010 by American Heart Association, Inc.