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Updated: May 23, 2026

Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Vasculitis, Atherosclerosis, and Altered HDL Composition in Heme-Oxygenase-1-Knockout Mice
Kazunobu Ishikawa1, Mohamad Navab, Aldons J Lusis
1The First Department of Internal Medicine and Center for Medical Education and Career Development, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1625, Japan.
Insights
Heme oxygenase-1 (HO-1) deficiency in mice causes severe arterial inflammation and lipid peroxidation. HO-1 plays a crucial role in preventing cardiovascular disease by suppressing inflammation and oxidative stress.
Area of Science:
- Cardiovascular Biology
- Immunology
- Biochemistry
Background:
- Heme oxygenase-1 (HO-1) is an enzyme with known cytoprotective functions.
- Its specific roles in the cardiovascular system, particularly in chronic inflammation and lipid metabolism, require further elucidation.
Purpose of the Study:
- To investigate the function of HO-1 in the cardiovascular system.
- To analyze the impact of HO-1 deficiency on arterial inflammation and lipid profiles in aged mice.
Main Methods:
- Analysis of one-year-old homozygous HO-1-knockout mice and wild-type littermates.
- Assessment of cardiovascular pathology, including aortitis and coronary arteritis.
- Measurement of plasma lipid levels (total cholesterol, HDL, triglyceride), HDL composition (apolipoprotein ratio), paraoxonase activity, and lipid hydroperoxides.
Main Results:
- HO-1-knockout mice exhibited severe aortitis and coronary arteritis with mononuclear cell infiltration and fatty streaks.
- Despite similar total cholesterol and HDL levels, knockout mice showed lower body weight and plasma triglyceride.
- HO-1 deficiency led to a significant alteration in HDL composition, a 10-fold reduction in apolipoprotein AI to AII ratio, decreased paraoxonase activity, and elevated plasma lipid hydroperoxides.
Conclusions:
- HO-1 deficiency promotes severe systemic arterial inflammation and atherosclerosis development, even on a standard diet.
- HO-1 plays a critical protective role against oxidative stress and lipid peroxidation in the cardiovascular system.
- These findings highlight HO-1 as a potential therapeutic target for cardiovascular diseases characterized by inflammation and oxidative damage.
Abstract:
To elucidate roles of heme oxygenase-1 (HO-1) in cardiovascular system, we have analyzed one-year-old HO-1-knockout mice. Homozygous HO-1-knockout mice had severe aortitis and coronary arteritis with mononuclear cellular infiltration and fatty streak formation even on a standard chow diet. Levels of plasma total cholesterol and HDL were similar among the three genotypes. However, homozygous HO-1-knockout mice had lower body weight and plasma triglyceride. HO-1-deficiency resulted in alteration of the composition of HDL. The ratio of apolipoprotein AI to AII in HO-1-knockout mice was reduced about 10-fold as compared to wild-type mice. In addition, paraoxonase, an enzyme against oxidative stress, was reduced less than 50% in HO-1-knockout mice. The knockout mice also exhibited significant elevation of plasma lipid hydroperoxides. This study using aged HO-1-knockout mice strengthened the idea that HO-1 functions to suppress systemic inflammation in artery wall and prevents plasma lipid peroxidation.
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