Inflammatory Ly6Chi monocytes and their conversion to M2 macrophages drive atherosclerosis regression

Rahman, Karishma; Vengrenyuk, Yuliya; Ramsey, Stephen A.; Rotllan, Noemí; Girgis, Natasha; Liu, Jianhua; Gusarova, Viktoria; Gromada, Jesper; Weinstock, Ada; Moore, Kathryn J.; Loke, P’ng; Fisher, Edward A.

doi:10.1172/jci75005

Cited by 295 publications

(305 citation statements)

References 54 publications

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“…It is initiated with the activation of endothelial cells, recruiting the circulating inflammatory monocytes, and neutrophils through adhesion molecules, such as VCAM‐1 and ICAM1, and promoted the permeability for LDL and other lipids, which could also stimulate inflammatory infiltration . Inflammation is essential to atherosclerosis, and monocytes/macrophages are critical participants, secreting IL‐1β, IL‐6, and TNF‐α, as well as the serum concentrations of some inflammation markers, are related to future cardiovascular risk . Here in our study, we found that circulating Ly6C hi and Ly6C lo monocytes and neutrophilia were dramatically increased in ApoE −/− mice, which were further elevated by Plin5 knockout.…”

Section: Discussionsupporting

confidence: 82%

Perilipin 5 deficiency promotes atherosclerosis progression through accelerating inflammation, apoptosis, and oxidative stress

Zhou

Han

et al. 2019

J of Cellular Biochemistry

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Excessive plasma triglyceride (TG) and cholesterol levels promote the progression of several prevalent cardiovascular risk factors, including atherosclerosis, which is a leading death cause. Perilipin 5 (Plin5), an important perilipin protein, is abundant in tissues with very active lipid catabolism and is involved in the regulation of oxidative stress. Although inﬂammation and oxidative stress play a critical role in atherosclerosis development, the underlying mechanisms are complex and not completely understood. In the present study, we demonstrated the role of Plin5 in high‐fat‐diet‐induced atherosclerosis in apolipoprotein E null (ApoE−/−) mice. Our results suggested that Plin5 expressions increased in the artery tissues of ApoE−/− mice. ApoE/Plin5 double knockout (ApoE−/−Plin5−/−) exacerbated severer atherogenesis, accompanied with significantly disturbed plasma metabolic profiles, such as elevated TG, total cholesterol, and low‐density lipoprotein cholesterol levels and reduced high‐density lipoprotein cholesterol contents. ApoE−/−Plin5−/− exhibited a higher number of inflammatory monocytes and neutrophils, as well as overexpression of cytokines and chemokines linked with an inflammatory response. Consistently, the IκBα/nuclear factor kappa B pathway was strongly activated in ApoE−/−Plin5−/−. Notably, apoptosis was dramatically induced by ApoE−/−Plin5−/−, as evidenced by increased cleavage of Caspase‐3 and Poly (ADP‐ribose) polymerase‐2. In addition, ApoE−/−Plin5−/− contributed to oxidative stress generation in the aortic tissues, which was linked with the activation of phosphatidylinositol 3‐kinase/protein kinase B and mitogen‐activated protein kinases pathways. In vitro, oxidized low‐density lipoprotein (ox‐LDL) increased Plin5 expression in RAW264.7 cells. Its knockdown enhanced inflammation, apoptosis, oxidative stress, and lipid accumulation, while promotion of Plin5 markedly reduced all the effects induced by ox‐LDL in cells. These studies strongly supported that Plin5 could be a new regulator against atherosclerosis, providing new insights on therapeutic solutions.

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Section: Discussionsupporting

confidence: 82%

Perilipin 5 deficiency promotes atherosclerosis progression through accelerating inflammation, apoptosis, and oxidative stress

Zhou

Han

et al. 2019

J of Cellular Biochemistry

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“…If applicable to atherosclerosis, the data from the Nr4a1-deficient mouse study above may suggest that Ly6 hi monocytes give rise to reparative macrophages in atherosclerotic lesions in a Nr4a1 -dependent manner. Consistent with this idea, a recent study shows that Ly6C hi monocytes are the source of resolving macrophages during atherosclerotic plaque regression (Rahman et al., 2017). …”

Section: Changes In Monocyte Dynamics Contribute To Atherogenesismentioning

confidence: 56%

Monocyte-Macrophages and T Cells in Atherosclerosis

2017

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Atherosclerosis is an arterial disease process characterized by the focal subendothelial accumulation of apolipoprotein B-lipoproteins, immune and vascular wall cells, and extracellular matrix. The lipoproteins acquire features of damage-associated molecular patterns and trigger first an innate immune response, dominated by monocyte-macrophages, and then an adaptive immune response. These inflammatory responses often become chronic and non-resolving, leading to arterial damage and thrombosis-induced organ infarction. The innate immune response is regulated at various stages, from hematopoiesis through monocyte changes and macrophage activation. The adaptive immune response is regulated primarily by mechanisms that affect the balance of regulatory vs. effector T cells. Mechanisms related to cellular cholesterol, phenotypic plasticity, metabolism, and aging play key roles in regulating these responses. Herein we review select topics that shed light on these processes and suggest new treatment strategies.

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“…Ly6C hi -monocyte-derived macrophages (Ly6C hi -MDMs) reside long-term within tissue, suggesting a link between inflammation severity, duration, and Ly6C hi monocyte-derived macrophage content (29). Furthermore, the importance of inflammatory Ly6C hi monocytes and their differentiation into M2 macrophages in atherosclerosis regression has been published very recently utilizing a mouse plaque transplant model (30), indicating that the observed decrease in inflammatory Ly6C hi monocytes impairs plaque regression and probably sup- 2 , a SOD2 activator, was determined and significantly reduced (n ≥ 11). (E) mRNA expression profile was compared with pre-MnCl 2 differentiation conditions using qPCR (n ≥ 5).…”

Section: Discussionmentioning

confidence: 99%

“…It is very likely that both mechanisms are of high importance for vascular inflammation and atherosclerosis development and progression. In both scenarios, macrophages and macrophage-like cells are of tremendous significance for atherosclerosis progression and regression (30,35).…”

Section: Discussionmentioning

confidence: 99%

Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis

Baumer¹,

Ng²,

Sanda³

et al. 2018

JCI Insight

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Inflammatory Ly6Chi monocytes and their conversion to M2 macrophages drive atherosclerosis regression

Cited by 295 publications

References 54 publications

Perilipin 5 deficiency promotes atherosclerosis progression through accelerating inflammation, apoptosis, and oxidative stress

Perilipin 5 deficiency promotes atherosclerosis progression through accelerating inflammation, apoptosis, and oxidative stress

Monocyte-Macrophages and T Cells in Atherosclerosis

Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis

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