P947 - IMPACT OF ANTIOXIDANT TREATMENT ON AORTA REMODELLING IN BALLOON-INJURED RABBITS FED A B VITAMIN AND CHOLINE DEFICIENT DIET – A PRECLINICAL MODEL OF ATHEROSCLEROSIS AND HYPERHOMOCYSTEINEMIA

P947

IMPACT OF ANTIOXIDANT TREATMENT ON AORTA REMODELLING IN BALLOON-INJURED RABBITS FED A B VITAMIN AND CHOLINE DEFICIENT DIET – A PRECLINICAL MODEL OF ATHEROSCLEROSIS AND HYPERHOMOCYSTEINEMIA

G. Almer^1,*, M. Brunner², C. Diwoky², M. Lechleitner³, G. Sommer⁴, F. Bogoni⁴, D. Kolb^5,6, G. Leitinger⁶, Y. Tehlivets², M. Kavertseva², A. Schwarz², V. Bubalo⁷, G. Rechberger², M. Herrmann¹, H. Mangge¹, S. Frank³, G. Holzapfel^4,8, D. Kratky³, G. Hörl⁹, O. Tehlivets^2,10

¹Medical University of Graz, Clinical Institute for Medical and Chemical Laboratory Diagnostics, ²University of Graz, Institute of Molecular Biosciences, ³Medical University of Graz, Gottfried Schatz Research Center, Molecular Biology and Biochemistry, ⁴Graz University of Technology, Institute of Biomechanics, ⁵Medical University of Graz, Center for Medical Research, Ultrastructure Analysis, ⁶Medical University of Graz, Gottfried Schatz Research Center, Cell Biology, Histology and Embryology, ⁷Medical University of Graz, Division of Biomedical Research, Graz, Austria, ⁸Norwegian University of Science and Technology, Department of Structural Engineering, Trondheim, Norway, ⁹Medical University of Graz, Otto Loewi Research Center, ¹⁰Medical University of Graz, Division of General Radiology, Department of Radiology, Graz, Austria

Rationale: The progression of atherosclerosis (AS) cannot be fully explained by established risk factors. Elevated plasma homocysteine (Hcy) is an independent risk factor and closely associated with cardiovascular mortality. However, its role in AS is not yet fully understood. Previous research in this area has been hampered by the lack of reproducible in vivo atherosclerotic models that mimic the human situation.

Methods: Here, we used an automated system for vascular wall injuries, which lead to more homogenous damage and improved atherosclerotic plaque development. Balloon-injured NZW rabbits were fed either a standard diet (SD) or a diet deficient in B vitamins and choline, which is required for Hcy degradation (VCDD). Alternatively, VCDD was administered in combination with the antioxidant N-acetyl cysteine (NAC) in liquid form (VCDD+NAC) to test for reversal of VCDD effects.

Results: We showed that, compared to SD, rabbits fed VCDD exhibited moderately increased plasma Hcy concentrations, aortic macrophage and lipid accumulation, aortic stiffening, and aortic collagen disorganization in the absence of hypercholesterolemia (HC), as well as aggravation of AS in the presence of HC. NAC application reduced plasma Hcy, aortic stiffening (p<0.01), and VCDD-induced neointima lipid accumulation to SD levels and increased fractional anisotropy (p<0.05), a marker of water diffusion through tissue. On the other hand, NAC deteriorated vascular wall contraction and relaxation (p<0.05) and increased plasma VLDL and LDL cholesterol, as well as VLDL and HDL triglycerides.

Conclusion: In summary, a diet deficient in nutrients required for Hcy degradation exacerbates atherosclerotic transformation independent of HC. NAC application partially reverses this effect but causes other effects that require further investigation.

Disclosure of Interest: None declared