β-Carotene conversion to vitamin A delays atherosclerosis progression by decreasing hepatic lipid secretion in mice

Felix Zhou, Xiaoyun Wu, Ivan Pinos, Benjamin M. Abraham, Tessa J. Barrett, Johannes von Lintig, Edward A. Fisher, Jaume Amengual

Research output: Contribution to journalArticlepeer-review

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 β-carotene with atherosclerosis, and we recently showed that β-carotene oxygenase 1 (BCO1) activity, responsible for β-carotene cleavage to vitamin A, is associated with reduced plasma cholesterol in humans and mice. In this study, we explore whether intact β-carotene or vitamin A affects atherosclerosis progression in the atheroprone LDLR-deficient mice. Compared with control-fed Ldlr-/- mice, β-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 β-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.

Original languageEnglish (US)
Pages (from-to)1491-1503
Number of pages13
JournalJournal of Lipid Research
Volume61
Issue number11
DOIs
StatePublished - Nov 2020

Keywords

  • Carotenoid
  • Carotenoids
  • Cholesterol
  • Foam cells
  • Liver
  • Low density lipoprotein-cholesterol
  • Oxygenases
  • Retinoic acid
  • Retinoids
  • Very low density lipoprotein

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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