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

32 Citations (Scopus)

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

Fingerprint

Hypercholesterolemia
Monocytes
Atherosclerosis
VLDL Lipoproteins
Cholesterol Esters
Apolipoproteins E
Intravenous Injections
High Fat Diet

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Foamy monocytes form early and contribute to nascent atherosclerosis in mice with hypercholesterolemia. / Xu, Lu; Dai Perrard, Xiaoyuan; Perrard, Jerry L.; Yang, Donglin; Xiao, Xinhua; Teng, Ba Bie; Simon, Scott I.; Ballantyne, Christie M.; Wu, Huaizhu.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 35, No. 8, 25.08.2015, p. 1787-1797.

Research output: Contribution to journalArticle

Xu, L, Dai Perrard, X, Perrard, JL, Yang, D, Xiao, X, Teng, BB, Simon, SI, Ballantyne, CM & Wu, H 2015, 'Foamy monocytes form early and contribute to nascent atherosclerosis in mice with hypercholesterolemia', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 35, no. 8, pp. 1787-1797. https://doi.org/10.1161/ATVBAHA.115.305609
Xu, Lu ; Dai Perrard, Xiaoyuan ; Perrard, Jerry L. ; Yang, Donglin ; Xiao, Xinhua ; Teng, Ba Bie ; Simon, Scott I. ; Ballantyne, Christie M. ; Wu, Huaizhu. / Foamy monocytes form early and contribute to nascent atherosclerosis in mice with hypercholesterolemia. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2015 ; Vol. 35, No. 8. pp. 1787-1797.
@article{0619e35d67bc4aed9d07fa83d9b4fc5f,
title = "Foamy monocytes form early and contribute to nascent atherosclerosis in mice with hypercholesterolemia",
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.",
keywords = "atherosclerosis, diet, high-fat, inflammation, lipoproteins, monocytes",
author = "Lu Xu and {Dai Perrard}, Xiaoyuan and Perrard, {Jerry L.} and Donglin Yang and Xinhua Xiao and Teng, {Ba Bie} and Simon, {Scott I.} and Ballantyne, {Christie M.} and Huaizhu Wu",
year = "2015",
month = "8",
day = "25",
doi = "10.1161/ATVBAHA.115.305609",
language = "English (US)",
volume = "35",
pages = "1787--1797",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "8",

}

TY - JOUR

T1 - Foamy monocytes form early and contribute to nascent atherosclerosis in mice with hypercholesterolemia

AU - Xu, Lu

AU - Dai Perrard, Xiaoyuan

AU - Perrard, Jerry L.

AU - Yang, Donglin

AU - Xiao, Xinhua

AU - Teng, Ba Bie

AU - Simon, Scott I.

AU - Ballantyne, Christie M.

AU - Wu, Huaizhu

PY - 2015/8/25

Y1 - 2015/8/25

N2 - 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.

AB - 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.

KW - atherosclerosis

KW - diet, high-fat

KW - inflammation

KW - lipoproteins

KW - monocytes

UR - http://www.scopus.com/inward/record.url?scp=84938069440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938069440&partnerID=8YFLogxK

U2 - 10.1161/ATVBAHA.115.305609

DO - 10.1161/ATVBAHA.115.305609

M3 - Article

VL - 35

SP - 1787

EP - 1797

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 8

ER -