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Updated: Jul 14, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Swings in blood glucose levels accelerate atherogenesis in apolipoprotein E-deficient mice
Tomoya Mita1, Aiko Otsuka, Kosuke Azuma
1Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Abstract:
The aim of this study was to investigate the effect of fluctuations in blood glucose levels on atherogenesis. Apolipoprotein (apo) E-deficient mice fed maltose twice daily were used as a model of repetitive postprandial glucose spikes. We investigated the number of macrophages adherent to the endothelium and the area of fibrotic arteriosclerotic lesions, with and without administration of miglitol, an alpha-glucosidase inhibitor. Macrophage adhesion to endothelial cells in thoracic aorta was quantitated by the en face method for optimal observation of endothelial surface after immunohistochemical staining for Mac-2. The area of arteriosclerotic lesions was measured in elastica van Giesson-stained proximal aorta. The number of adherent macrophages increased at 1 week after commencement of maltose feeding and the size of arteriosclerotic lesion increased at 5 weeks after such feeding. These increases were prevented by simultaneous use of miglitol. Our data demonstrated that glucose fluctuations accelerate atherogenesis. This was independent of changes in serum cholesterol level in vivo. Reduction of glucose fluctuation by alpha-glucosidase inhibitor efficiently controlled the progression of atherosclerosis.
Insights
Repetitive blood glucose spikes accelerate atherosclerosis by increasing macrophage adhesion and lesion size. An alpha-glucosidase inhibitor effectively prevented this progression, independent of cholesterol levels.
Area of Science:
- Cardiovascular Research
- Metabolic Syndrome
- Atherosclerosis Pathogenesis
Background:
- Atherosclerosis is a complex disease influenced by various metabolic factors.
- The role of postprandial glucose fluctuations, independent of sustained hyperglycemia, in atherogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the impact of repetitive postprandial glucose spikes on the development of atherosclerosis.
- To evaluate the efficacy of an alpha-glucosidase inhibitor in mitigating glucose fluctuation-induced atherogenesis.
Main Methods:
- Utilized apolipoprotein (apo) E-deficient mice as a model for induced glucose spikes via maltose feeding.
- Quantified macrophage adhesion to the thoracic aorta endothelium using immunohistochemical staining (Mac-2).
- Measured the area of fibrotic arteriosclerotic lesions in the proximal aorta using elastica van Giesson staining.
- Assessed the effects of miglitol, an alpha-glucosidase inhibitor, on these parameters.
Main Results:
- Maltose feeding led to increased macrophage adhesion within 1 week and enlarged arteriosclerotic lesions by 5 weeks.
- Simultaneous administration of miglitol significantly prevented both increased macrophage adhesion and lesion development.
- The atherogenic effects of glucose fluctuations were observed independently of changes in serum cholesterol levels.
Conclusions:
- Glucose fluctuations, not just average glucose levels, significantly accelerate atherogenesis.
- Inhibition of alpha-glucosidase effectively reduces glucose fluctuations and controls the progression of atherosclerosis.
- This highlights a novel therapeutic target for managing cardiovascular disease risk associated with metabolic dysregulation.
