mTOR mediates the cross-talk of macrophage polarization and autophagy in atherosclerosis

Tian, Feng; Yu, Bin; Hu, Jiarui

doi:10.1016/j.ijcard.2014.09.035

Cited by 20 publications

(14 citation statements)

References 15 publications

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“…Also, activation of autophagy in macrophages through mTOR inhibition was reported to lead to stabilization of atherosclerotic plaque in mice. 45 These data support also the protective role of autophagic activity in macrophages in atherosclerosis ( Figure 2). Macrophage subtype named Mox, presented in murine atherosclerosis different patterns of gene expression than other subtypes (M1, classically classified as pro-inflammatory and M2, anti-inflammatory) including redox-regulated genes; furthermore, Mox showed decreased autophagic activity compared with M1 and M2 in mice.…”

Section: Role Of Autophagy In Atherosclerotic Cell Typessupporting

confidence: 71%

“…Moore et al 47 reported the capacity of macrophages to promote plaque regression by changing phenotype in atherosclerosis via administration of the M2-driving cytokine IL-13 to mice. At the same time, Tian et al 45 reported that induction of autophagy drives macrophages towards the M2 phenotype. It is known that macrophages with impaired autophagy cannot be cleared by efferocytosis; in contrast, these macrophages become apoptotic, and the inflammasome pathway may be activated leading to lesion progression (Figure 2).…”

Section: Role Of Autophagy In Atherosclerotic Cell Typesmentioning

confidence: 96%

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A role for autophagy in carotid atherosclerosis

Alloza

Goikuria

Freijo

et al. 2016

European Stroke Journal

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Purpose: Autophagy has emerged in recent years as a critical cellular survival mechanism for cell homeostasis and may play a protective role in atherosclerosis. We aimed to review here the role autophagy plays in different cell types present in carotid atherosclerotic plaques and that may be associated with the development of unstable carotid atheroma plaque. Methods: We performed a thorough literature exploration in this area of research covering the three main cell types present in carotid atheroma plaques. Findings: Reviewed reports indicate that the role of autophagy in stable or unstable carotid atherosclerotic plaques depends on the different cell types and phenotypes, the stage and morphology of the plaque and the specific autophagy factor/s involved. Discussion: Although defective autophagy could be one of the causes for carotid atheroma plaques to become unstable, it is important to take into account that autophagic players can act differentially in different cell types and different stages of the developed plaque. Conclusion: This review provides an overview of the role of autophagy in the main cell types in carotid atherosclerosis (i.e. macrophages, endothelial cells and smooth muscle cells).

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Section: Role Of Autophagy In Atherosclerotic Cell Typessupporting

confidence: 71%

Section: Role Of Autophagy In Atherosclerotic Cell Typesmentioning

confidence: 96%

A role for autophagy in carotid atherosclerosis

Alloza

Goikuria

Freijo

et al. 2016

European Stroke Journal

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“…Previous reports show that defective phagocytic clearance of macrophages promotes plaque necrosis and inhibition of autophagy by silencing ATG5 or other autophagy mediators to enhance protective processes in atherosclerosis [22]. Furthermore, mTOR mediates cross talk of macrophage polarization and autophagy in atherosclerosis [30]. However, the polarization and autophagy of foam cells in the pathogenesis of atherosclerosis remain largely unexplained.…”

Section: Discussionmentioning

confidence: 99%

Rapamycin and FTY720 Alleviate Atherosclerosis by Cross Talk of Macrophage Polarization and Autophagy

Sun

Fan

Liang

et al. 2018

BioMed Research International

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Foam cell formation and macrophage polarization are involved in the pathologic development of atherosclerosis, one of the most important human diseases affecting large and medium artery walls. This study was designed to assess the effects of rapamycin and FTY720 (fingolimod) on macrophages and foam cells. Mouse peritoneal macrophages were collected and treated with rapamycin and FTY720 to study autophagy, polarization, and lipid accumulation. Next, foam cells were formed by oxidizing low-density lipoprotein to observe changes in lipid accumulation, autophagy, and polarization in rapamycin-treated or FTY720-treated foam cells. Lastly, foam cells that had been treated with rapamycin and FTY720 were evaluated for sphingosine 1-phosphate receptor (S1prs) expression. Autophagy microtubule-associated protein 1 light chain 3- (LC3-) II was increased, and classically activated macrophage phenotype markers interleukin- (IL-) 6, cyclooxygenase-2 (COX2), and inducible nitric oxide synthase (iNOS) were increased, whereas alternatively activated macrophage phenotype markers transforming growth factor- (TGF-) β, arginase 1 (Arg1), and mannose receptor C-type 1 (Mrc1) were decreased by rapamycin in peritoneal macrophages. LC3-II was also obviously enhanced, though polarization markers were unchanged in rapamycin-treated foam cells. Moreover, lipid accumulation was inhibited in rapamycin-treated macrophage cells but was unchanged in rapamycin-treated foam cells. For FTY720, LC3-II did not change, whereas TGF-β, Arg1 and Mrc1 were augmented, and IL-6 was suppressed in macrophages. However, LC3-II was increased, and TGF-β, ARG1 and MRC1 were strikingly augmented, whereas IL-6, COX2 and iNOS could be suppressed in foam cells. Furthermore, lipid accumulation was alleviated in FTY720-treated foam cells. Additionally, S1pr1 was markedly decreased in foam cells (P < .05); S1pr2, S1pr3, S1pr4 and S1pr5 were unchanged in rapamycin-treated foam cells. In FTY720-treated foam cells, S1pr3 and S1pr4 were decreased, and S1pr1, S1pr2 and S1pr5 were unchanged. Therefore, we deduced that rapamycin stimulated classically activated macrophages and supressed early atherosclerosis. Rapamycin may also stabilize artery plaques by preventing apoptosis and S1PR1 in advanced atherosclerosis. FTY720 allowed transformation of foam cells into alternatively activated macrophages through the autophagy pathway to alleviate advanced atherosclerosis.

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“…Insulin resistance and hyperglycemia are associated with diabetic atherosclerosis, and endothelial dysfunction, vascular inflammation, myeloid cell recruitment, oxidative stress, VSMC phenotype changes, and platelet hyperreactivity all contribute to diabetic atherosclerosis. As reported recently, crosstalk between macrophage polarization and autophagy may be involved in diabetes and related atherosclerosis complications [ 133 , 134 ]. Extensive preclinical studies have identified the molecule targets and herbs that act on these targets as potential therapeutic agents for the management of diabetic atherosclerosis (see Table 2 ).…”

Section: Future Perspectivesmentioning

confidence: 96%

Cellular and Molecular Mechanisms of Diabetic Atherosclerosis: Herbal Medicines as a Potential Therapeutic Approach

Tian

Liu

et al. 2017

Oxidative Medicine and Cellular Longevity

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An increasing number of patients diagnosed with diabetes mellitus eventually develop severe coronary atherosclerosis disease. Both type 1 and type 2 diabetes mellitus increase the risk of cardiovascular disease associated with atherosclerosis. The cellular and molecular mechanisms affecting the incidence of diabetic atherosclerosis are still unclear, as are appropriate strategies for the prevention and treatment of diabetic atherosclerosis. In this review, we discuss progress in the study of herbs as potential therapeutic agents for diabetic atherosclerosis.

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mTOR mediates the cross-talk of macrophage polarization and autophagy in atherosclerosis

Cited by 20 publications

References 15 publications

A role for autophagy in carotid atherosclerosis

A role for autophagy in carotid atherosclerosis

Rapamycin and FTY720 Alleviate Atherosclerosis by Cross Talk of Macrophage Polarization and Autophagy

Cellular and Molecular Mechanisms of Diabetic Atherosclerosis: Herbal Medicines as a Potential Therapeutic Approach

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