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Updated: Sep 19, 2025
A Rabbit Aortic Valve Stenosis Model Induced by Direct Balloon Injury
Published on: March 31, 2023
Homocysteine leads to aortic stiffening in a rabbit model of atherosclerosis
Francesca Bogoni1, Markus S Brunner2, Gunter Almer3
1Institute of Biomechanics, Graz University of Technology, Austria.
Insights
Elevated homocysteine (hyperhomocysteinemia) stiffens aortas, increasing cardiovascular disease risk. B vitamin deficiency alone causes aortic stiffening, independent of cholesterol, highlighting its role in atherosclerosis.
Area of Science:
- Cardiovascular Science
- Biomedical Engineering
- Nutritional Science
Background:
- Hyperhomocysteinemia is an independent risk factor for cardiovascular disease and atherosclerosis.
- The impact of elevated homocysteine on aortic biomechanics remains under-investigated.
- Understanding these biomechanical changes is crucial for developing targeted interventions.
Purpose of the Study:
- To investigate the effects of hyperhomocysteinemia and hypercholesterolemia on abdominal aortic biomechanics in a rabbit model.
- To elucidate the independent and combined roles of B vitamin deficiency and high cholesterol in altering aortic mechanical properties.
- To assess the influence of homocysteine levels on stress-stretch relationships, mechanical anisotropy, and tissue inelasticity.
Main Methods:
- An animal model was established in rabbits, inducing hyperhomocysteinemia and hypercholesterolemia via specific diets and homocysteine injections.
- Abdominal aortas were subjected to equibiaxial and non-equibiaxial extension tests to evaluate mechanical properties.
- Microstructural histological analyses supported the mechanical characterization of aortic tissues.
Main Results:
- A diet deficient in B vitamins and choline induced aortic stiffening, even without hypercholesterolemia, suggesting an independent role in atherosclerosis.
- Increased homocysteine levels, achieved through intravenous injections in deficient rabbits, led to a stiffer stress response.
- Elevated homocysteine also resulted in more pronounced inelastic phenomena in the aortic tissue compared to controls.
Conclusions:
- B vitamin and choline deficiency can independently contribute to aortic stiffening and potentially atherosclerosis.
- Elevated homocysteine levels significantly alter aortic biomechanics, exacerbating tissue stiffening and inelasticity.
- This study provides critical insights into the mechanical consequences of metabolic dysregulation on vascular health.
Abstract:
Hyperhomocysteinemia, an elevated level of homocysteine in the blood, is an independent risk factor for atherosclerosis and, more generally, cardiovascular disease. However, its relationship with aortic biomechanics has not been investigated yet. To better understand the influence of elevated homocysteine levels on aortic biomechanics, we propose an animal model in which hyperhomocysteinemia, hypercholesterolemia, and their combination were induced in rabbits by balloon injury of the abdominal aorta, special diets, and intravenous homocysteine injections. The effects of a diet deficient in B vitamins and choline, which are required for homocysteine degradation, a cholesterol-rich diet, their combination, and increased homocysteine concentration are investigated in relation to abdominal aortic biomechanics in rabbits. For this purpose, equibiaxial and non-equibiaxial extension tests were carried out, and the influence of risk factors on the stress-stretch relationship, mechanical anisotropy, and tissue inelasticity is discussed. The mechanical characterization of the tissue was supported by microstructural histological analyses. Our study reveals that deficiency of B vitamins and choline cause aortic stiffening even in the absence of hypercholesterolemia, suggesting a possible independent role in the development of atherosclerosis. Further increasing homocysteine concentration through intravenous injections in rabbits fed B vitamins and choline-deficient diet also results in a stiffer stress response and more pronounced inelastic phenomena with respect to the control group.
