Foamy monocytes form early and contribute to nascent atherosclerosis in mice with hypercholesterolemia

Lu Xu, Xiaoyuan Dai Perrard, Jerry L. Perrard, Donglin Yang, Xinhua Xiao, Ba Bie Teng, Scott I. Simon, Christie M. Ballantyne, Huaizhu Wu

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Objective - To examine infiltration of blood foamy monocytes, containing intracellular lipid droplets, into early atherosclerotic lesions and its contribution to development of nascent atherosclerosis. Approach and Results - In apoE -/- mice fed Western high-fat diet (WD), >10% of circulating monocytes became foamy monocytes at 3 days on WD and >20% of monocytes at 1 week. Foamy monocytes also formed early in blood of Ldlr -/- Apobec1 -/- (LDb) mice on WD. Based on CD11c and CD36, mouse monocytes were categorized as CD11c - CD36 -, CD11c - CD36 +, and CD11c + CD36 +. The majority of foamy monocytes were CD11c + CD36 +, whereas most nonfoamy monocytes were CD11c - CD36 - or CD11c - CD36 + in apoE -/- mice on WD. In wild-type mice, CD11c + CD36 + and CD11c - CD36 +, but few CD11c - CD36 -, monocytes took up cholesteryl ester-rich very low-density lipoproteins (CE-VLDLs) isolated from apoE -/- mice on WD, and CE-VLDL uptake accelerated CD11c - CD36 + to CD11c + CD36 + monocyte differentiation. Ablation of CD36 decreased monocyte uptake of CE-VLDLs. Intravenous injection of DiI-CE-VLDLs in apoE -/- mice on WD specifically labeled CD11c + CD36 + foamy monocytes, which infiltrated into nascent atherosclerotic lesions and became CD11c + cells that were selectively localized in atherosclerotic lesions. CD11c deficiency reduced foamy monocyte infiltration into atherosclerotic lesions. Specific and consistent depletion of foamy monocytes (for 3 weeks) by daily intravenous injections of low-dose clodrosome reduced development of nascent atherosclerosis. Conclusions - Foamy monocytes, which form early in blood of mice with hypercholesterolemia, infiltrate into early atherosclerotic lesions in a CD11c-dependent manner and play crucial roles in nascent atherosclerosis development.

Original languageEnglish (US)
Pages (from-to)1787-1797
Number of pages11
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume35
Issue number8
DOIs
StatePublished - Aug 25 2015

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Keywords

  • atherosclerosis
  • diet, high-fat
  • inflammation
  • lipoproteins
  • monocytes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Xu, L., Dai Perrard, X., Perrard, J. L., Yang, D., Xiao, X., Teng, B. B., Simon, S. I., Ballantyne, C. M., & Wu, H. (2015). Foamy monocytes form early and contribute to nascent atherosclerosis in mice with hypercholesterolemia. Arteriosclerosis, Thrombosis, and Vascular Biology, 35(8), 1787-1797. https://doi.org/10.1161/ATVBAHA.115.305609