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Elevation of homocysteine levels in the plasma leads to deregulation of lipid metabolism in a rabbit model of atherosclerosis
Author(s) -
Tehlivets Oksana,
Brunner Markus,
Almer Gunter,
Schoiswohl Gabriele,
Wolinski Heimo,
Kolb Dagmar,
Kravets Volodymyr,
Ortner Melanie,
Schwarz Andreas,
Opriessnig Peter,
Hörl Gerd,
GroseljStrele Andrea,
Höfler Gerald,
Kratky Dagmar,
Mangge Harald,
Rechberger Gerald
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.05203
Subject(s) - medicine , homocysteine , endocrinology , hyperhomocysteinemia , lipid metabolism , phosphatidylethanolamine , sphingomyelin , population , chemistry , choline , phosphatidylcholine , phospholipid , biology , cholesterol , biochemistry , environmental health , membrane
Cardiovascular disease, the leading cause of death worldwide, is in the majority of cases a result of atherosclerosis, which can be only to 50% explained by established risk factors including hypercholesterolemia (HCL). Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. It is linked to numerous human diseases, strongly correlates with cardiovascular and all‐cause mortality, and is associated with deregulation of lipid metabolism. HHcy is found in 5‐10% of the general population and up to 30% of the elderly, and is mainly due to genetic defects or vitamin deficiency resulting in blocking of homocysteine (Hcy) degradation. We induced HHcy by dietary partial blocking of Hcy degradation and intravenous injections of Hcy into a rabbit model of atherosclerosis in the presence or absence of HCL. Deficiency of vitamins and choline required for Hcy degradation in the absence of HCL leads to an accumulation of lipid droplets in cells of the aorta including endothelial cells, smooth muscle cells, and fibroblasts, an accumulation of dilated ER in fibroblasts of the aorta as well as decreased LPC18:1 and 18:2 levels in muscles. In addition, while dietary blocking of Hcy degradation results in increased triacylglycerol (TAG) concentrations in blood cells, further elevation of Hcy levels leads to their decrease, but also to ceramide, lyso‐phosphatidylcholine (LPC), phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin accumulation in blood cells, compared to the diet blocking Hcy degradation alone. A decrease of TAG levels was also observed in the liver, in response to intravenous injections of Hcy and in rabbits receiving a combined diet that blocked Hcy degradation and induced HCL. In conclusion our data suggest that dietary blocking of Hcy degradation as well as Hcy itself may contribute to different human pathologies by deregulation of lipid metabolism in different tissues.