Ovid Technologies (Wolters Kluwer Health)

Circulation Research

, volume 130 , issue 6 , pages 831-847

Autophagy Is Differentially Regulated in Leukocyte and Nonleukocyte Foam Cells During Atherosclerosis

Sabrina Robichaud ^{1, 2}

Adil Rasheed ^{1, 2}

Antonietta Pietrangelo ^{1, 2}

Anne Doyoung Kim ^{1, 2}

Dominique M. Boucher ^{1, 2}

Christina Emerton ¹

Viyashini Vijithakumar ^{1, 2}

Lara Gharibeh ^{1, 2}

Garrett Fairman ^{1, 2}

Esther Mak ¹

My-Anh Nguyen ^{1, 2}

Michele Geoffrion ¹

Robert Wirka ³

Katey J Rayner ^{1, 2}

Mireille Ouimet ^{1, 2}

Hide authors affiliations Show authors affiliations: 3 affiliations

University of Ottawa Heart Institute, ON (S.R., A.R., A.P., A.D.K., D.M.B., C.E., V.V., L.G., G.F., E.M., M.-A.N., M.G., K.J.R., M.O.). |

Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, ON (S.R., A.R., A.P., A.D.K., D.M.B., V.V., L.G., G.F., M.-A.N., K.J.R., M.O.). |

University of North Carolina School of Medicine, Chapel Hill (R.W.). |

Publication type: Journal Article

Publication date: 2022-02-09

Ovid Technologies (Wolters Kluwer Health)

Circulation Research

scimago Q1

wos Q1

SJR: 4.897

CiteScore: 24.2

Impact factor: 16.2

ISSN: 00097330, 15244571

DOI: 10.1161/CIRCRESAHA.121.320047

Copy DOI

PubMed ID: 35137605

Cardiology and Cardiovascular Medicine

Physiology

Abstract

Rationale:

Atherosclerosis is characterized by an accumulation of foam cells within the arterial wall, resulting from excess cholesterol uptake and buildup of cytosolic lipid droplets (LDs). Autophagy promotes LD clearance by freeing stored cholesterol for efflux, a process that has been shown to be atheroprotective. While the role of autophagy in LD catabolism has been studied in macrophage-derived foam cells, this has remained unexplored in vascular smooth muscle cell (VSMC)-derived foam cells that constitute a large fraction of foam cells within atherosclerotic lesions.

Objective:

We performed a comparative analysis of autophagy flux in lipid-rich aortic intimal populations to determine whether VSMC-derived foam cells metabolize LDs similarly to their macrophage counterparts.

Methods and Results:

Atherosclerosis was induced in GFP-LC3 (microtubule-associated proteins 1A/1B light chain 3) transgenic mice by PCSK9 (proprotein convertase subtilisin/kexin type 9)-adeno-associated viral injection and Western diet feeding. Using flow cytometry of aortic digests, we observed a significant increase in dysfunctional autophagy of VSMC-derived foam cells during atherogenesis relative to macrophage-derived foam cells. Using cell culture models of lipid-loaded VSMCs and macrophages, we show that autophagy-mediated cholesterol efflux from VSMC foam cells was poor relative to macrophage foam cells, and largely occurs when HDL (high-density lipoprotein) was used as a cholesterol acceptor, as opposed to apoA-1 (apolipoproteinA-1). This was associated with the predominant expression of ABCG1 in VSMC foam cells. Using metformin, an autophagy activator, cholesterol efflux to HDL was significantly increased in VSMC, but not in macrophage, foam cells.

Conclusions:

These data demonstrate that VSMC and macrophage foam cells perform cholesterol efflux by distinct mechanisms, and that autophagy flux is highly impaired in VSMC foam cells, but can be induced by pharmacological means. Further investigation is warranted into targeting autophagy specifically in VSMC foam cells, the predominant foam cell subtype of advanced atherosclerotic plaques, to promote reverse cholesterol transport and resolution of the atherosclerotic plaque.

Found

Top-30

Journals

	1 2 3
International Journal of Molecular Sciences	International Journal of Molecular Sciences, 3, 4.05% International Journal of Molecular Sciences 3 publications, 4.05%
Biomedicine and Pharmacotherapy	Biomedicine and Pharmacotherapy, 3, 4.05% Biomedicine and Pharmacotherapy 3 publications, 4.05%
Biomolecules	Biomolecules, 2, 2.7% Biomolecules 2 publications, 2.7%
Cell Death and Disease	Cell Death and Disease, 2, 2.7% Cell Death and Disease 2 publications, 2.7%
Current Atherosclerosis Reports	Current Atherosclerosis Reports, 2, 2.7% Current Atherosclerosis Reports 2 publications, 2.7%
Current Problems in Cardiology	Current Problems in Cardiology, 2, 2.7% Current Problems in Cardiology 2 publications, 2.7%
Journal of Advanced Research	Journal of Advanced Research, 2, 2.7% Journal of Advanced Research 2 publications, 2.7%
ACS Nano	ACS Nano, 2, 2.7% ACS Nano 2 publications, 2.7%
Journal of Nanobiotechnology	Journal of Nanobiotechnology, 2, 2.7% Journal of Nanobiotechnology 2 publications, 2.7%
Metabolism: Clinical and Experimental	Metabolism: Clinical and Experimental, 2, 2.7% Metabolism: Clinical and Experimental 2 publications, 2.7%
Journal of Translational Medicine	Journal of Translational Medicine, 1, 1.35% Journal of Translational Medicine 1 publication, 1.35%
Current Opinion in Lipidology	Current Opinion in Lipidology, 1, 1.35% Current Opinion in Lipidology 1 publication, 1.35%
Circulation Research	Circulation Research, 1, 1.35% Circulation Research 1 publication, 1.35%
Frontiers in Physiology	Frontiers in Physiology, 1, 1.35% Frontiers in Physiology 1 publication, 1.35%
Frontiers in Genetics	Frontiers in Genetics, 1, 1.35% Frontiers in Genetics 1 publication, 1.35%
Advanced Functional Materials	Advanced Functional Materials, 1, 1.35% Advanced Functional Materials 1 publication, 1.35%
Clinical and Experimental Medicine	Clinical and Experimental Medicine, 1, 1.35% Clinical and Experimental Medicine 1 publication, 1.35%
WIREs Mechanisms of Disease	WIREs Mechanisms of Disease, 1, 1.35% WIREs Mechanisms of Disease 1 publication, 1.35%
Nature Reviews Cardiology	Nature Reviews Cardiology, 1, 1.35% Nature Reviews Cardiology 1 publication, 1.35%
The Analyst	The Analyst, 1, 1.35% The Analyst 1 publication, 1.35%
Microvascular Research	Microvascular Research, 1, 1.35% Microvascular Research 1 publication, 1.35%
FASEB Journal	FASEB Journal, 1, 1.35% FASEB Journal 1 publication, 1.35%
Phytotherapy Research	Phytotherapy Research, 1, 1.35% Phytotherapy Research 1 publication, 1.35%
Cardiology	Cardiology, 1, 1.35% Cardiology 1 publication, 1.35%
Science China Life Sciences	Science China Life Sciences, 1, 1.35% Science China Life Sciences 1 publication, 1.35%
Expert Opinion on Therapeutic Targets	Expert Opinion on Therapeutic Targets, 1, 1.35% Expert Opinion on Therapeutic Targets 1 publication, 1.35%
Frontiers in Cardiovascular Medicine	Frontiers in Cardiovascular Medicine, 1, 1.35% Frontiers in Cardiovascular Medicine 1 publication, 1.35%
European Journal of Medical Research	European Journal of Medical Research, 1, 1.35% European Journal of Medical Research 1 publication, 1.35%
Phytomedicine	Phytomedicine, 1, 1.35% Phytomedicine 1 publication, 1.35%
	1 2 3

Publishers

	2 4 6 8 10 12 14 16 18
Elsevier	Elsevier, 17, 22.97% Elsevier 17 publications, 22.97%
Springer Nature	Springer Nature, 15, 20.27% Springer Nature 15 publications, 20.27%
MDPI	MDPI, 8, 10.81% MDPI 8 publications, 10.81%
Frontiers Media S.A.	Frontiers Media S.A., 5, 6.76% Frontiers Media S.A. 5 publications, 6.76%
Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 5, 6.76% Cold Spring Harbor Laboratory 5 publications, 6.76%
American Chemical Society (ACS)	American Chemical Society (ACS), 5, 6.76% American Chemical Society (ACS) 5 publications, 6.76%
Ovid Technologies (Wolters Kluwer Health)	Ovid Technologies (Wolters Kluwer Health), 4, 5.41% Ovid Technologies (Wolters Kluwer Health) 4 publications, 5.41%
Wiley	Wiley, 4, 5.41% Wiley 4 publications, 5.41%
Royal Society of Chemistry (RSC)	Royal Society of Chemistry (RSC), 2, 2.7% Royal Society of Chemistry (RSC) 2 publications, 2.7%
Taylor & Francis	Taylor & Francis, 2, 2.7% Taylor & Francis 2 publications, 2.7%
Oxford University Press	Oxford University Press, 2, 2.7% Oxford University Press 2 publications, 2.7%
Federation of American Societies for Experimental Biology (FASEB)	Federation of American Societies for Experimental Biology (FASEB), 1, 1.35% Federation of American Societies for Experimental Biology (FASEB) 1 publication, 1.35%
S. Karger AG	S. Karger AG, 1, 1.35% S. Karger AG 1 publication, 1.35%
Research Square Platform LLC	Research Square Platform LLC, 1, 1.35% Research Square Platform LLC 1 publication, 1.35%
Impact Journals	Impact Journals, 1, 1.35% Impact Journals 1 publication, 1.35%
AME Publishing Company	AME Publishing Company, 1, 1.35% AME Publishing Company 1 publication, 1.35%
	2 4 6 8 10 12 14 16 18

We do not take into account publications without a DOI.
Statistics recalculated weekly.

Are you a researcher?

Create a profile to get free access to personal recommendations for colleagues and new articles.

Metrics

Cite this

GOST |

Cite this

GOST Copy

Robichaud S. et al. Autophagy Is Differentially Regulated in Leukocyte and Nonleukocyte Foam Cells During Atherosclerosis // Circulation Research. 2022. Vol. 130. No. 6. pp. 831-847.

GOST all authors (up to 50) Copy

Robichaud S., Rasheed A., Pietrangelo A., Doyoung Kim A., Boucher D. M., Emerton C., Vijithakumar V., Gharibeh L., Fairman G., Mak E., Nguyen M., Geoffrion M., Wirka R., Rayner K. J., Ouimet M. Autophagy Is Differentially Regulated in Leukocyte and Nonleukocyte Foam Cells During Atherosclerosis // Circulation Research. 2022. Vol. 130. No. 6. pp. 831-847.

RIS |

Cite this

RIS Copy

TY - JOUR

DO - 10.1161/CIRCRESAHA.121.320047

UR - https://doi.org/10.1161/CIRCRESAHA.121.320047

TI - Autophagy Is Differentially Regulated in Leukocyte and Nonleukocyte Foam Cells During Atherosclerosis

T2 - Circulation Research

AU - Robichaud, Sabrina

AU - Rasheed, Adil

AU - Pietrangelo, Antonietta

AU - Doyoung Kim, Anne

AU - Boucher, Dominique M.

AU - Emerton, Christina

AU - Vijithakumar, Viyashini

AU - Gharibeh, Lara

AU - Fairman, Garrett

AU - Mak, Esther

AU - Nguyen, My-Anh

AU - Geoffrion, Michele

AU - Wirka, Robert

AU - Rayner, Katey J

AU - Ouimet, Mireille

PY - 2022

DA - 2022/02/09

PB - Ovid Technologies (Wolters Kluwer Health)

SP - 831-847

IS - 6

VL - 130

PMID - 35137605

SN - 0009-7330

SN - 1524-4571

ER -

BibTex |

Cite this

BibTex (up to 50 authors) Copy

@article{2022_Robichaud,

author = {Sabrina Robichaud and Adil Rasheed and Antonietta Pietrangelo and Anne Doyoung Kim and Dominique M. Boucher and Christina Emerton and Viyashini Vijithakumar and Lara Gharibeh and Garrett Fairman and Esther Mak and My-Anh Nguyen and Michele Geoffrion and Robert Wirka and Katey J Rayner and Mireille Ouimet},

title = {Autophagy Is Differentially Regulated in Leukocyte and Nonleukocyte Foam Cells During Atherosclerosis},

journal = {Circulation Research},

year = {2022},

volume = {130},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

month = {feb},

url = {https://doi.org/10.1161/CIRCRESAHA.121.320047},

number = {6},

pages = {831--847},

doi = {10.1161/CIRCRESAHA.121.320047}

}

MLA

Cite this

MLA Copy

Robichaud, Sabrina, et al. “Autophagy Is Differentially Regulated in Leukocyte and Nonleukocyte Foam Cells During Atherosclerosis.” Circulation Research, vol. 130, no. 6, Feb. 2022, pp. 831-847. https://doi.org/10.1161/CIRCRESAHA.121.320047.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Journal

Circulation Research

scimago Q1

wos Q1

SJR

4.897

CiteScore

24.2

Impact factor

16.2

ISSN

00097330 (Print)

15244571 (Electronic)