ß-Carotene conversion to vitamin A delays atherosclerosis progression by decreasing hepatic lipid secretion in mice.
J Lipid Res
; 61(11): 1491-1503, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32963037
ABSTRACT
Atherosclerosis is characterized by the pathological accumulation of cholesterol-laden macrophages in the arterial wall. Atherosclerosis is also the main underlying cause of CVDs, and its development is largely driven by elevated plasma cholesterol. Strong epidemiological data find an inverse association between plasma ß-carotene with atherosclerosis, and we recently showed that ß-carotene oxygenase 1 (BCO1) activity, responsible for ß-carotene cleavage to vitamin A, is associated with reduced plasma cholesterol in humans and mice. In this study, we explore whether intact ß-carotene or vitamin A affects atherosclerosis progression in the atheroprone LDLR-deficient mice. Compared with control-fed Ldlr-/- mice, ß-carotene-supplemented mice showed reduced atherosclerotic lesion size at the level of the aortic root and reduced plasma cholesterol levels. These changes were absent in Ldlr-/- /Bco1-/- mice despite accumulating ß-carotene in plasma and atherosclerotic lesions. We discarded the implication of myeloid BCO1 in the development of atherosclerosis by performing bone marrow transplant experiments. Lipid production assays found that retinoic acid, the active form of vitamin A, reduced the secretion of newly synthetized triglyceride and cholesteryl ester in cell culture and mice. Overall, our findings provide insights into the role of BCO1 activity and vitamin A in atherosclerosis progression through the regulation of hepatic lipid metabolism.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vitamina A
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Beta Caroteno
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Aterosclerose
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Lipídeos
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Fígado
Limite:
Animals
Idioma:
En
Revista:
J Lipid Res
Ano de publicação:
2020
Tipo de documento:
Article