Homocysteine contributes to atherogenic transformation of the aorta in rabbits in the absence of hypercholesterolemia.

Autor: Tehlivets O; Institute of Molecular Biosciences, University of Graz, Graz, Austria; Division of General Radiology, Department of Radiology, Medical University of Graz, Graz, Austria. Electronic address: oksana.tehlivets@uni-graz.at., Almer G; Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria., Brunner MS; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Lechleitner M; Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria., Sommer G; Institute of Biomechanics, Graz University of Technology, Graz, Austria., Kolb D; Gottfried Schatz Research Center, Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria; Center for Medical Research, Ultrastructure Analysis, Medical University of Graz, Graz, Austria., Leitinger G; Gottfried Schatz Research Center, Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria., Diwoky C; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Wolinski H; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Habisch H; Otto Loewi Research Center, Medicinal Chemistry, Medical University of Graz, Graz, Austria., Opriessnig P; Division of General Neurology, Department of Neurology, Medical University of Graz, Graz, Austria; Division of Pediatric Radiology, Department of Radiology, Medical University of Graz, Graz, Austria., Bogoni F; Institute of Biomechanics, Graz University of Technology, Graz, Austria., Pernitsch D; Center for Medical Research, Ultrastructure Analysis, Medical University of Graz, Graz, Austria., Kavertseva M; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Bourgeois B; Otto Loewi Research Center, Medicinal Chemistry, Medical University of Graz, Graz, Austria., Kukilo J; Institute of Biomechanics, Graz University of Technology, Graz, Austria., Tehlivets YG; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Schwarz AN; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Züllig T; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Bubalo V; Division of Biomedical Research, Medical University of Graz, Graz, Austria., Schauer S; Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria., Groselj-Strele A; Center for Medical Research, Computational Bioanalytics, Medical University of Graz, Graz, Austria., Hoefler G; Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria., Rechberger GN; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Herrmann M; Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria., Eller K; Clinical Division of Nephrology, Medical University of Graz, Graz, Austria., Rosenkranz AR; Clinical Division of Nephrology, Medical University of Graz, Graz, Austria., Madl T; Otto Loewi Research Center, Medicinal Chemistry, Medical University of Graz, Graz, Austria., Frank S; Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria., Holzapfel GA; Institute of Biomechanics, Graz University of Technology, Graz, Austria; Department of Structural Engineering, Norwegian University of Science and Technology, Trondheim, Norway., Kratky D; Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria., Mangge H; Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria., Hörl G; Otto Loewi Research Center, Medicinal Chemistry, Medical University of Graz, Graz, Austria.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Sep; Vol. 178, pp. 117244. Date of Electronic Publication: 2024 Aug 09.
DOI: 10.1016/j.biopha.2024.117244
Abstrakt: Atherosclerosis, the leading cause of cardiovascular disease, cannot be sufficiently explained by established risk factors, including cholesterol. Elevated plasma homocysteine (Hcy) is an independent risk factor for atherosclerosis and is closely linked to cardiovascular mortality. However, its role in atherosclerosis has not been fully clarified yet. We have previously shown that rabbits fed a diet deficient in B vitamins and choline (VCDD), which are required for Hcy degradation, exhibit an accumulation of macrophages and lipids in the aorta, aortic stiffening and disorganization of aortic collagen in the absence of hypercholesterolemia, and an aggravation of atherosclerosis in its presence. In the current study, plasma Hcy levels were increased by intravenous injections of Hcy into balloon-injured rabbits fed VCDD (VCDD+Hcy) in the absence of hypercholesterolemia. While this treatment did not lead to thickening of aortic wall, intravenous injections of Hcy into rabbits fed VCDD led to massive accumulation of VLDL-triglycerides as well as significant impairment of vascular reactivity of the aorta compared to VCDD alone. In the aorta intravenous Hcy injections into VCDD-fed rabbits led to fragmentation of aortic elastin, accumulation of elastin-specific electron-dense inclusions, collagen disorganization, lipid degradation, and autophagolysosome formation. Furthermore, rabbits from the VCDD+Hcy group exhibited a massive decrease of total protein methylated arginine in blood cells and decreased creatine in blood cells, serum and liver compared to rabbits from the VCDD group. Altogether, we conclude that Hcy contributes to atherogenic transformation of the aorta not only in the presence but also in the absence of hypercholesterolemia.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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