CD36-dependent 7-ketocholesterol accumulation in macrophages mediates progression of atherosclerosis in response to chronic air pollution exposure

Xiaoquan Rao, Jixin Zhong, Andrei Maiseyeu, Bhavani Gopalakrishnan, Frederick A. Villamena, Lung Chi Chen, Jack R. Harkema, Qinghua Sun, Sanjay Rajagopalan

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Rationale: Air pollution exposure has been shown to potentiate plaque progression in humans and animals. Our previous studies have suggested a role for oxidized lipids in mediating adverse vascular effect of air pollution. However, the types of oxidized lipids formed in response to air pollutants and how this occurs and their relevance to atherosclerosis are not fully understood. Objective: To investigate the mechanisms by which particulate matter <2.5 μm (PM2.5) induces progression of atherosclerosis. Methods and Results: Atherosclerosis-prone ApoE-/- or LDLR-/- mice were exposed to filtered air or concentrated ambient PM2.5 using a versatile aerosol concentrator enrichment system for 6 months. PM2.5 increased 7-ketocholesterol (7-KCh), an oxidatively modified form of cholesterol, in plasma intermediate density lipoprotein/low-density lipoprotein fraction and in aortic plaque concomitant with progression of atherosclerosis and increased CD36 expression in plaque macrophages from PM2.5-exposed mice. Macrophages isolated from PM2.5-exposed mice displayed increased uptake of oxidized lipids without alterations in their efflux capacity. Consistent with these finding, CD36-positive macrophages displayed a heightened capacity for oxidized lipid uptake. Deficiency of CD36 on hematopoietic cells diminished the effect of air pollution on 7-KCh accumulation, foam cell formation, and atherosclerosis. Conclusions: Our results suggest a potential role for CD36-mediated abnormal accumulations of oxidized lipids, such as 7-KCh , in air pollution-induced atherosclerosis progression. (Circ Res. 2014;115:770-780.)

Original languageEnglish (US)
Pages (from-to)770-780
Number of pages11
JournalCirculation research
Volume115
Issue number9
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Air Pollution
Atherosclerosis
Macrophages
Lipids
IDL Lipoproteins
Air Pollutants
Foam Cells
Particulate Matter
Apolipoproteins E
Aerosols
LDL Lipoproteins
Blood Vessels
7-ketocholesterol
Cholesterol
Air

Keywords

  • 7-ketocholesterol
  • Air pollution
  • Atherosclerosis
  • Foam cells
  • Macrophages
  • Particulate matter

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

CD36-dependent 7-ketocholesterol accumulation in macrophages mediates progression of atherosclerosis in response to chronic air pollution exposure. / Rao, Xiaoquan; Zhong, Jixin; Maiseyeu, Andrei; Gopalakrishnan, Bhavani; Villamena, Frederick A.; Chen, Lung Chi; Harkema, Jack R.; Sun, Qinghua; Rajagopalan, Sanjay.

In: Circulation research, Vol. 115, No. 9, 01.01.2014, p. 770-780.

Research output: Contribution to journalArticle

Rao, X, Zhong, J, Maiseyeu, A, Gopalakrishnan, B, Villamena, FA, Chen, LC, Harkema, JR, Sun, Q & Rajagopalan, S 2014, 'CD36-dependent 7-ketocholesterol accumulation in macrophages mediates progression of atherosclerosis in response to chronic air pollution exposure', Circulation research, vol. 115, no. 9, pp. 770-780. https://doi.org/10.1161/CIRCRESAHA.115.304666
Rao, Xiaoquan ; Zhong, Jixin ; Maiseyeu, Andrei ; Gopalakrishnan, Bhavani ; Villamena, Frederick A. ; Chen, Lung Chi ; Harkema, Jack R. ; Sun, Qinghua ; Rajagopalan, Sanjay. / CD36-dependent 7-ketocholesterol accumulation in macrophages mediates progression of atherosclerosis in response to chronic air pollution exposure. In: Circulation research. 2014 ; Vol. 115, No. 9. pp. 770-780.
@article{b14fded145184224a9a47cde8bd53f01,
title = "CD36-dependent 7-ketocholesterol accumulation in macrophages mediates progression of atherosclerosis in response to chronic air pollution exposure",
abstract = "Rationale: Air pollution exposure has been shown to potentiate plaque progression in humans and animals. Our previous studies have suggested a role for oxidized lipids in mediating adverse vascular effect of air pollution. However, the types of oxidized lipids formed in response to air pollutants and how this occurs and their relevance to atherosclerosis are not fully understood. Objective: To investigate the mechanisms by which particulate matter <2.5 μm (PM2.5) induces progression of atherosclerosis. Methods and Results: Atherosclerosis-prone ApoE-/- or LDLR-/- mice were exposed to filtered air or concentrated ambient PM2.5 using a versatile aerosol concentrator enrichment system for 6 months. PM2.5 increased 7-ketocholesterol (7-KCh), an oxidatively modified form of cholesterol, in plasma intermediate density lipoprotein/low-density lipoprotein fraction and in aortic plaque concomitant with progression of atherosclerosis and increased CD36 expression in plaque macrophages from PM2.5-exposed mice. Macrophages isolated from PM2.5-exposed mice displayed increased uptake of oxidized lipids without alterations in their efflux capacity. Consistent with these finding, CD36-positive macrophages displayed a heightened capacity for oxidized lipid uptake. Deficiency of CD36 on hematopoietic cells diminished the effect of air pollution on 7-KCh accumulation, foam cell formation, and atherosclerosis. Conclusions: Our results suggest a potential role for CD36-mediated abnormal accumulations of oxidized lipids, such as 7-KCh , in air pollution-induced atherosclerosis progression. (Circ Res. 2014;115:770-780.)",
keywords = "7-ketocholesterol, Air pollution, Atherosclerosis, Foam cells, Macrophages, Particulate matter",
author = "Xiaoquan Rao and Jixin Zhong and Andrei Maiseyeu and Bhavani Gopalakrishnan and Villamena, {Frederick A.} and Chen, {Lung Chi} and Harkema, {Jack R.} and Qinghua Sun and Sanjay Rajagopalan",
year = "2014",
month = "1",
day = "1",
doi = "10.1161/CIRCRESAHA.115.304666",
language = "English (US)",
volume = "115",
pages = "770--780",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

TY - JOUR

T1 - CD36-dependent 7-ketocholesterol accumulation in macrophages mediates progression of atherosclerosis in response to chronic air pollution exposure

AU - Rao, Xiaoquan

AU - Zhong, Jixin

AU - Maiseyeu, Andrei

AU - Gopalakrishnan, Bhavani

AU - Villamena, Frederick A.

AU - Chen, Lung Chi

AU - Harkema, Jack R.

AU - Sun, Qinghua

AU - Rajagopalan, Sanjay

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Rationale: Air pollution exposure has been shown to potentiate plaque progression in humans and animals. Our previous studies have suggested a role for oxidized lipids in mediating adverse vascular effect of air pollution. However, the types of oxidized lipids formed in response to air pollutants and how this occurs and their relevance to atherosclerosis are not fully understood. Objective: To investigate the mechanisms by which particulate matter <2.5 μm (PM2.5) induces progression of atherosclerosis. Methods and Results: Atherosclerosis-prone ApoE-/- or LDLR-/- mice were exposed to filtered air or concentrated ambient PM2.5 using a versatile aerosol concentrator enrichment system for 6 months. PM2.5 increased 7-ketocholesterol (7-KCh), an oxidatively modified form of cholesterol, in plasma intermediate density lipoprotein/low-density lipoprotein fraction and in aortic plaque concomitant with progression of atherosclerosis and increased CD36 expression in plaque macrophages from PM2.5-exposed mice. Macrophages isolated from PM2.5-exposed mice displayed increased uptake of oxidized lipids without alterations in their efflux capacity. Consistent with these finding, CD36-positive macrophages displayed a heightened capacity for oxidized lipid uptake. Deficiency of CD36 on hematopoietic cells diminished the effect of air pollution on 7-KCh accumulation, foam cell formation, and atherosclerosis. Conclusions: Our results suggest a potential role for CD36-mediated abnormal accumulations of oxidized lipids, such as 7-KCh , in air pollution-induced atherosclerosis progression. (Circ Res. 2014;115:770-780.)

AB - Rationale: Air pollution exposure has been shown to potentiate plaque progression in humans and animals. Our previous studies have suggested a role for oxidized lipids in mediating adverse vascular effect of air pollution. However, the types of oxidized lipids formed in response to air pollutants and how this occurs and their relevance to atherosclerosis are not fully understood. Objective: To investigate the mechanisms by which particulate matter <2.5 μm (PM2.5) induces progression of atherosclerosis. Methods and Results: Atherosclerosis-prone ApoE-/- or LDLR-/- mice were exposed to filtered air or concentrated ambient PM2.5 using a versatile aerosol concentrator enrichment system for 6 months. PM2.5 increased 7-ketocholesterol (7-KCh), an oxidatively modified form of cholesterol, in plasma intermediate density lipoprotein/low-density lipoprotein fraction and in aortic plaque concomitant with progression of atherosclerosis and increased CD36 expression in plaque macrophages from PM2.5-exposed mice. Macrophages isolated from PM2.5-exposed mice displayed increased uptake of oxidized lipids without alterations in their efflux capacity. Consistent with these finding, CD36-positive macrophages displayed a heightened capacity for oxidized lipid uptake. Deficiency of CD36 on hematopoietic cells diminished the effect of air pollution on 7-KCh accumulation, foam cell formation, and atherosclerosis. Conclusions: Our results suggest a potential role for CD36-mediated abnormal accumulations of oxidized lipids, such as 7-KCh , in air pollution-induced atherosclerosis progression. (Circ Res. 2014;115:770-780.)

KW - 7-ketocholesterol

KW - Air pollution

KW - Atherosclerosis

KW - Foam cells

KW - Macrophages

KW - Particulate matter

UR - http://www.scopus.com/inward/record.url?scp=84921931895&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921931895&partnerID=8YFLogxK

U2 - 10.1161/CIRCRESAHA.115.304666

DO - 10.1161/CIRCRESAHA.115.304666

M3 - Article

VL - 115

SP - 770

EP - 780

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 9

ER -