Related Experiment Video
Updated: Aug 18, 2026
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
The antioxidant N-acetylcysteine prevents accelerated atherosclerosis in uremic apolipoprotein E knockout mice
Ognen Ivanovski1, Dorota Szumilak, Thao Nguyen-Khoa
1INSERM Unit 507, Necker Hospital, Paris, France. ivanovski@necker.fr
Insights
The antioxidant N-acetylcysteine (NAC) reduces atherosclerosis progression in a mouse model of chronic renal failure (CRF). NAC treatment decreased oxidative stress and plaque collagen, offering a potential therapeutic strategy for cardiovascular disease in CRF patients.
Area of Science:
- Nephrology
- Cardiology
- Biochemistry
Background:
- Cardiovascular disease (CVD) is a leading cause of mortality in chronic renal failure (CRF).
- N-acetylcysteine (NAC), an antioxidant, has demonstrated potential in reducing cardiovascular events in hemodialysis patients.
- This study investigates NAC's direct impact on uremia-exacerbated atherosclerosis.
Purpose of the Study:
- To evaluate the efficacy of N-acetylcysteine (NAC) supplementation in mitigating atherosclerosis in a mouse model of chronic renal failure (CRF).
- To explore the underlying mechanisms, particularly the role of oxidative stress, in NAC's effects on atheroma progression.
Main Methods:
- Uremia was surgically induced in apolipoprotein E-deficient (apoE(-/-)) mice.
- Mice received daily oral N-acetylcysteine (NAC) or placebo for 8 weeks.
- Atherosclerotic plaque size and collagen content were measured in the aorta.
Main Results:
- Uremic apoE(-/-) mice exhibited significantly larger atherosclerotic lesions and increased aortic nitrotyrosine and collagen content compared to controls.
- N-acetylcysteine (NAC) treatment significantly inhibited the progression of atherosclerotic lesions and reduced plaque collagen.
- NAC treatment decreased nitrotyrosine expression in plaques, indicating reduced oxidative stress, without affecting macrophage infiltration or blood pressure.
Conclusions:
- N-acetylcysteine (NAC) effectively reduces atheroma progression in an animal model of uremia-enhanced atherosclerosis.
- The findings suggest that NAC's beneficial effects are likely mediated by a reduction in oxidative stress.
- NAC represents a potential therapeutic agent for managing atherosclerosis in patients with chronic renal failure.
Background:
Cardiovascular disease is the most frequent cause of mortality in chronic renal failure (CRF). Therefore, it is important to identify appropriate treatment measures. The antioxidant N-acetylcysteine (NAC) has been shown to reduce cardiovascular events in hemodialysis patients. Here we examine a possible direct effect of NAC supplementation on uremia-enhanced atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice.
Methods:
Uremia was induced surgically in 8-week-old female apoE(-/-) mice. Two weeks after creation of CRF mice were randomized to receive either NAC (daily oral gavage with 200 mg/kg for 8 weeks) or placebo. They were compared to a control group of sham-operated apoE(-/-) mice receiving placebo. After 8 weeks of treatment, the mice were sacrificed, and the cross-section surface area of atherosclerotic plaques was measured in aortic root and descending aorta.
Results:
At 10 weeks following surgery, atherosclerotic lesions were significantly larger in uremic apoE(-/-) mice than in nonuremic controls. This accelerated atherosclerosis was associated with an increase in aortic nitrotyrosine expression and collagen plaque content. NAC treatment inhibited the progression of atherosclerotic lesions and plaque collagen content compared with placebo treatment. In addition, plaques from NAC-treated uremic animals showed a significant decrease in nitrotyrosine expression whereas the degree of macrophage infiltration was comparable in both uremic groups. There was no difference in mean arterial blood pressure between the three groups.
Conclusion:
We show for the first time that the antioxidant NAC is capable of reducing atheroma progression, in an animal model of uremia-enhanced atherosclerosis, probably via a decrease in oxidative stress.
