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Updated: Jul 16, 2026

Aggravation of Myocardial Ischemia upon Particulate Matter Exposure in Atherosclerosis Animal Model
Published on: December 10, 2021
Chronic intermittent hypoxia induces atherosclerosis
Vladimir Savransky1, Ashika Nanayakkara, Jianguo Li
1Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
Insights
Chronic intermittent hypoxia (CIH) combined with a high-cholesterol diet induces atherosclerosis in mice. This study establishes a link between CIH, dyslipidemia, and the development of atherosclerotic lesions.
Area of Science:
- Cardiovascular Research
- Sleep Medicine
- Metabolic Disorders
Background:
- Obstructive sleep apnea is linked to hyperlipidemia, atherosclerosis, and cardiovascular risk.
- A direct causal relationship between obstructive sleep apnea and atherosclerosis remains unproven.
Purpose of the Study:
- To investigate if chronic intermittent hypoxia (CIH) can induce atherosclerosis.
- To examine the role of CIH in the development of atherosclerotic lesions in a mouse model.
Main Methods:
- Male C57BL/6J mice were fed either a high-cholesterol or regular diet.
- Mice were exposed to either CIH or intermittent air (control) for 12 weeks.
Main Results:
- Mice on a high-cholesterol diet exposed to CIH developed atherosclerotic lesions.
- No atherosclerosis was observed in mice on a high-cholesterol diet with normal air or mice on a regular diet with CIH.
- CIH exacerbated diet-induced dyslipidemia, increasing lipid peroxidation and altering hepatic lipoprotein secretion.
Conclusions:
- Chronic intermittent hypoxia promotes atherosclerosis development.
- Diet-induced dyslipidemia is a critical factor in CIH-induced atherosclerosis.
Rationale:
Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia (CIH), is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established.
Objectives:
The objective of the present study was to examine whether CIH may induce atherosclerosis in C57BL/6J mice.
Methods:
Forty male C57BL/6J mice, 8 weeks of age, were fed either a high-cholesterol diet or a regular chow diet and subjected either to CIH or intermittent air (control conditions) for 12 weeks.
Measurements And Main Results:
Nine of 10 mice simultaneously exposed to CIH and high-cholesterol diet developed atherosclerotic lesions in the aortic origin and descending aorta. In contrast, atherosclerosis was not observed in mice exposed to intermittent air and a high-cholesterol diet or in mice exposed to CIH and a regular diet. A high-cholesterol diet resulted in significant increases in serum total and low-density lipoprotein cholesterol levels and a decrease in high-density lipoprotein cholesterol. Compared with mice exposed to intermittent air and a high-cholesterol diet, combined exposure to CIH and a high-cholesterol diet resulted in marked progression of dyslipidemia with further increases in serum total cholesterol and low-density lipoprotein cholesterol (124 +/- 4 vs. 106 +/- 6 mg/dl; p < 0.05), a twofold increase in serum lipid peroxidation, and up-regulation of an important hepatic enzyme of lipoprotein secretion, stearoyl-coenzyme A desaturase-1.
Conclusions:
CIH causes atherosclerosis in the presence of diet-induced dyslipidemia.
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