Universität zu Köln

Asare, Yaw, Koehncke, Janine, Selle, Jaco, Simsekyilmaz, Sakine, Jankowski, Joachim, Shagdarsuren, Gansuvd ORCID: 0000-0003-1388-5795, Gessner, Johannes E., Bernhagen, Juergen and Shagdarsuren, Erdenechimeg (2020). Differential Role for Activating Fc gamma RIII in Neointima Formation After Arterial Injury and Diet-Induced Chronic Atherosclerosis inApolipoprotein E-Deficient Mice. Front. Physiol., 11. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-042X

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Abstract

Atherogenesis and arterial remodeling following mechanical injury are driven by inflammation and mononuclear cell infiltration. The binding of immune complexes (ICs) to immunoglobulin (Ig)-Fc gamma receptors (Fc gamma Rs) on most innate and adaptive immune cells induces a variety of inflammatory responses that promote atherogenesis. Here, we studied the role of Fc gamma RIII in neointima formation after arterial injury in atherosclerosis-prone mice and compared the outcome and mechanism to that of Fc gamma RIII in diet-induced chronic atherosclerosis.Fc gamma rIII(-/-)/Apoe(-/-)and controlApoe(-/-)mice were subjected to wire-induced endothelial denudation of the carotid artery while on high-fat diet (HFD).Fc gamma rIIIdeficiency mitigated neointimal plaque formation and lesional macrophage accumulation, and enhanced neointimal vascular smooth muscle cell (VSMC) numbers. This went along with a reduced expression of tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1/CCL2), and vascular cell adhesion molecule-1 (VCAM-1) in the neointimal lesions. Interestingly, in a chronic model of diet-induced atherosclerosis, we unraveled a dichotomic role of Fc gamma RIII in an early versus advanced stage of the disease. WhileFc gamma rIIIdeficiency conferred atheroprotection in the early stage, it promoted atherosclerosis in advanced stages. To this end,Fc gamma rIIIdeficiency attenuated pro-inflammatory responses in early atherosclerosis but promoted these events in advanced stages. Analysis of the mechanism(s) underlying the athero-promoting effect ofFc gamma rIIIdeficiency in late-stage atherosclerosis revealed increased serum levels of anti-oxidized-LDL immunoglobulins IgG2c and IgG2b. This was paralleled by enhanced lesional accumulation of IgGs without affecting levels of complement-activated products C5a or C5ar1, Fc gamma RII, and Fc gamma RIV. Moreover,Fc gamma rIII-deficient macrophages expressed moreFc gamma rII,Tnf-alpha, andIl-1 beta mRNA when exposed to IgG1 or oxLDL-IgG1 ICsin vitro, and peripheral CD4+ and CD8+ T-cell levels were altered. Collectively, our data suggest that deficiency of activatingFc gamma RIIIlimits neointima formation after arterial injury in atherosclerosis-prone mice as well as early stage chronic atherosclerosis, but augments late-stage atherosclerosis suggesting a dual role of Fc gamma RIII in atherogenic inflammation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Asare, Yaw UNSPECIFIED UNSPECIFIED UNSPECIFIED Koehncke, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Selle, Jaco UNSPECIFIED UNSPECIFIED UNSPECIFIED Simsekyilmaz, Sakine UNSPECIFIED UNSPECIFIED UNSPECIFIED Jankowski, Joachim UNSPECIFIED UNSPECIFIED UNSPECIFIED Shagdarsuren, Gansuvd UNSPECIFIED orcid.org/0000-0003-1388-5795 UNSPECIFIED Gessner, Johannes E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bernhagen, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Shagdarsuren, Erdenechimeg UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-329717
DOI:	10.3389/fphys.2020.00673
Journal or Publication Title:	Front. Physiol.
Volume:	11
Date:	2020
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-042X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LOW-DENSITY-LIPOPROTEIN; IMMUNE-COMPLEXES; IGG; RECEPTORS; PROGRESSION; INHIBITION; MECHANISMS; PROTECTION; ANTIBODIES; LESIONS Multiple languages Physiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32971