Fat mass and obesity-associated protein attenuates lipid accumulation in macrophage foam cells and alleviates atherosclerosis in apolipoprotein E-deficient mice

Mo, Chunfen; Yang, Ming; Han, Xiaobin; Li, Junhong; Gao, Guangping; Tai, Haoran; Huang, Ning; Xiao, Hengyi

doi:10.1097/hjh.0000000000001255

Cited by 31 publications

(26 citation statements)

References 44 publications

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“…Reducing lipid-laden and inflamed macrophages within atherosclerotic plaques may also be an important strategy for reducing cardiovascular events 240 . In addition to lowering LDL-C, AMPK activation in response to salicylate and A769662 enhances reverse cholesterol efflux from macrophages owing to upregulation of the transport proteins ATP-binding cassette subfamily A member 1 (ABCA1) and ABCG1 (REFS 249,250 ), or by increasing scavenger receptor class B type 1 (SRB1)-mediated hepatic delivery 246 . AMPK suppression of macrophage inflammation within plaques 228,230,251 and adipose tissue 219 may also be important for suppressing atherosclerosis development.…”

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confidence: 99%

AMP-activated protein kinase: the current landscape for drug development

Steinberg

Carling

2019

Nat Rev Drug Discov

445

405

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Since the discovery of AMP-activated protein kinase (AMPK) as a central regulator of energy homeostasis, many exciting insights into its structure, regulation and physiological roles have been revealed. While exercise, caloric restriction, metformin and many natural products increase AMPK activity and exert a multitude of health benefits, developing direct activators of AMPK to elucidate the role of AMPK in these beneficial effects has been challenging. However, in recent years, direct AMPK activators have been identified and tested in preclinical models, and a small number have entered clinical trials. Despite these advances, which disease(s) represent the best indications for therapeutic AMPK activation and the long-term safety of such approaches remain to be established. Commented [WS2]: Au: "The optimal consensus motif of AMPK substrates has been established (BOX 3)" OK?

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Section: ) (Table 1)mentioning

confidence: 99%

AMP-activated protein kinase: the current landscape for drug development

Steinberg

Carling

2019

Nat Rev Drug Discov

445

405

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“…The role of m6A methylation in the development and progression of vascular calcification, 110 obesity-induced vascular dysfunction, 70 atherosclerosis 111 and angiogenesis 16 has been explored. Atherosclerosis is the most prevalent disease threatening the vasculature, and is characteristic by lipid deposition and fiber cap formation.…”

Section: Atherosclerosismentioning

confidence: 99%

“… 112 Mo and colleagues found that overexpression of FTO by adeno-associated virus serotype 9 (AAV9) significantly reduced the lipidic profiles including plasma total cholesterol and LDL cholesterol, resulting in preventing the formation of atherosclerotic plaques. 111 However, Kruger et al demonstrated that loss of endothelial FTO prevented obesity-induced vascular dysfunction by using endothelial FTO-deficient mice. 70 It may be reasonable that FTO exerts different effects in different cell types.…”

Section: Atherosclerosismentioning

confidence: 99%

The critical roles of m6A modification in metabolic abnormality and cardiovascular diseases

et al. 2021

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N6-methyladenosine (m6A) RNA methylation is an emerging area of epigenetics, which is a reversible and dynamic modification mediating by ‘writers’ (methylase, adding methyl groups, METTL3, METTL14, and WTAP), ‘erasers’ (demethylase, deleting methyl groups, FTO and ALKBH5), and ‘readers’ (YTHDF1-3, YTHDC1 and YTHDC2). Recent studies in human, animal models and cell levels have disclosed a critical role of m6A modification in regulating the homeostasis of metabolic processes and cardiovascular function. Evidence from these studies identify m6A as a candidate of biomarker and therapeutic target for metabolic abnormality and cardiovascular diseases (CVD). Comprehensive understanding of the complexity of m6A regulation in metabolic diseases and CVD will be helpful for us to understand the pathogenesis of CVD. In this review, we discuss the regulatory role of m6A in metabolic abnormality and CVD. We will emphasize the clinical relevance of m6A dysregulation in CVD.

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“…On the one hand, very-low-density lipoproteins, LDLs, and lipoproteins invade and accumulate in the vascular wall, resulting in the thickening of the vascular intima and narrowing of the lumen. Monocytes differentiate into macrophages and phagocytose a large amount of lipids to transform into foam cells, promoting the development of AS [16]. On the other hand, foam cells secrete several inflammatory factors—such as TNF-α, interleukin-1 (IL-1), and IL-6—which further leads to cellular adhesion, infiltration of inflammatory cells, and matrix degradation, resulting in atherosclerotic plaque rupture [15].…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers in macrophages of atherosclerosis by microarray analysis

et al. 2019

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Background Atherosclerotic cardiovascular disease (ASCVD) refers to a series of diseases caused by atherosclerosis (AS). It is one of the most important causes of death worldwide. According to the inflammatory response theory, macrophages play a critical role in AS. However, the potential targets associated with macrophages in the development of AS are still obscure. This study aimed to use bioinformatics tools for screening and identifying molecular targets in AS macrophages. Methods Two expression profiling datasets (GSE7074 and GSE9874) were obtained from the Gene Expression Omnibus dataset, and differentially expressed genes (DEGs) between non-AS macrophages and AS macrophages were identified. Functional annotation of the DEGs was performed by analyzing the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. STRING and Cytoscape were employed for constructing a protein–protein interaction network and analyzing hub genes. Results A total of 98 DEGs were distinguished between non-AS macrophages and AS macrophages. The functional variations in DEGs were mainly enriched in response to hypoxia, respiratory gaseous exchange, protein binding, and intracellular, ciliary tip, early endosome membrane, and Lys63-specific deubiquitinase activities. Three genes were identified as hub genes, including KDELR3 , CD55 , and DYNC2H1 . Conclusion Hub genes and DEGs identified by using microarray techniques can be used as diagnostic and therapeutic biomarkers for AS.

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Fat mass and obesity-associated protein attenuates lipid accumulation in macrophage foam cells and alleviates atherosclerosis in apolipoprotein E-deficient mice

Abstract: We propose that the FTO-dependent control of cholesterol deposition may provide avenues for the treatment of atherosclerosis.

Cited by 31 publications

References 44 publications

AMP-activated protein kinase: the current landscape for drug development

AMP-activated protein kinase: the current landscape for drug development

The critical roles of m6A modification in metabolic abnormality and cardiovascular diseases

Identification of biomarkers in macrophages of atherosclerosis by microarray analysis

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