Targeting Foam Cell Formation in Atherosclerosis: Therapeutic Potential of Natural Products

Wang, Dongdong; Yang, Yang; Yue, Lei; Tzvetkov, Nikolay; Liu, Xingde; Yeung, Andy Wai Kan; Xu, Suowen; Atanasov, Atanas G.

doi:10.1124/pr.118.017178

Cited by 124 publications

(81 citation statements)

References 885 publications

(1,207 reference statements)

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“…This conclusion stems from the knowledge that, without being ingested by neighboring vital macrophages, old macrophage foam cells die, they trigger an inflammatory response, and their bodies build up to form an ever-growing necrotic lipid core, which ultimately renders the plaque susceptible to rupture and cause even fatal atherothrombotic complications. Therefore, understanding cellular Ca 2+ metabolism and the related molecules/pathways which are involved in the generation of foam cells and in decreased efferocytic engulfment of ACs are of great importance when considering to attenuate the progression of atherosclerotic lesions [18]. In this regard, Ca 2+ plays a physiological and anti-atherosclerotic role by promoting the migration and survival of macrophages, and by enhancing the secretion of anti-inflammatory cytokines by them.…”

Section: Therapeutic Aspectsmentioning

confidence: 99%

“…Statins are a class of drugs which inhibit the activity of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, the rate-controlling enzyme in the pathway of cholesterol biosynthesis [176]. They increase the activity of hepatic low-density lipoprotein receptors and thereby hepatic uptake of circulating LDL-particles, which lower the concentration of plasma LDL-cholesterol [177] and successfully decrease CVD, MI, and ischemic stroke [18,178,179]. Statins are divided in two main groups, hydrophilic statins such as fluvastatin, rosuvastatin, and pravastatin and lipophilic statins such as atorvastatin as well as simvastatin [18].…”

Section: Therapeutic Aspectsmentioning

confidence: 99%

“…They increase the activity of hepatic low-density lipoprotein receptors and thereby hepatic uptake of circulating LDL-particles, which lower the concentration of plasma LDL-cholesterol [177] and successfully decrease CVD, MI, and ischemic stroke [18,178,179]. Statins are divided in two main groups, hydrophilic statins such as fluvastatin, rosuvastatin, and pravastatin and lipophilic statins such as atorvastatin as well as simvastatin [18]. Interestingly, of the statins, both hydrophilic statins (fluvastatin and pravastatin) and a lipophilic statin (atorvastatin) have been found to inhibit inorganic phosphate-induced apoptosis and the related calcification of culture VSMCs via the Gas6-mediated survival pathway [180,181].…”

Section: Therapeutic Aspectsmentioning

confidence: 99%

“…A large and ever-growing body of literature has demonstrated that the most important steps in the formation of atherosclerotic plaques are the accumulation of inflammatory cells (viz. macrophages and dendritic cells), foam cell formation, and defective efferocytic removal of ACs in the plaques [17,18]. Most importantly, defective efferocytosis of inflammatory apoptotic macrophages and macrophage foam cells results in their secondary necrosis and thereby contributes to the formation of an enlarged necrotic core, which weakens the plaque and makes it susceptible to rupture [19].…”

Section: Introductionmentioning

confidence: 99%

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Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

Tajbakhsh

Kovanen

Rezaee

et al. 2019

JCM

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In atherosclerosis, macrophages in the arterial wall ingest plasma lipoprotein-derived lipids and become lipid-filled foam cells with a limited lifespan. Thus, efficient removal of apoptotic foam cells by efferocytic macrophages is vital to preventing the dying foam cells from forming a large necrotic lipid core, which, otherwise, would render the atherosclerotic plaque vulnerable to rupture and would cause clinical complications. Ca 2+ plays a role in macrophage migration, survival, and foam cell generation. Importantly, in efferocytic macrophages, Ca 2+ induces actin polymerization, thereby promoting the formation of a phagocytic cup necessary for efferocytosis. Moreover, in the efferocytic macrophages, Ca 2+ enhances the secretion of anti-inflammatory cytokines. Various Ca 2+ antagonists have been seminal for the demonstration of the role of Ca 2+ in the multiple steps of efferocytosis by macrophages. Moreover, in vitro and in vivo experiments and clinical investigations have revealed the capability of Ca 2+ antagonists in attenuating the development of atherosclerotic plaques by interfering with the deposition of lipids in macrophages and by reducing plaque calcification. However, the regulation of cellular Ca 2+ fluxes in the processes of efferocytic clearance of apoptotic foam cells and in the extracellular calcification in atherosclerosis remains unknown. Here, we attempted to unravel the molecular links between Ca 2+ and efferocytosis in atherosclerosis and to evaluate cellular Ca 2+ fluxes as potential treatment targets in atherosclerotic cardiovascular diseases.

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Section: Therapeutic Aspectsmentioning

confidence: 99%

Section: Therapeutic Aspectsmentioning

confidence: 99%

Section: Therapeutic Aspectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

Tajbakhsh

Kovanen

Rezaee

et al. 2019

JCM

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“…2 Mono-nuclear cells migrate to the sub-endothelial to be activated and differentiated into macrophages, and macrophages can phagocytose modified low-density lipoprotein to form early foam cells when the scavenger receptor is activated. 3,4 Foam cells will rupture and die with this constant accumulation of lipids. 5 Foam cells, therefore, serve not only as marker cells for the early stage of arteriosclerosis 6 but also participate in the entire atherosclerotic lesion process.…”

Section: Introductionmentioning

confidence: 99%

<p>Isoborneol Attenuates Low-Density Lipoprotein Accumulation and Foam Cell Formation in Macrophages</p>

Wang¹,

Li²,

Liu³

et al. 2020

DDDT

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Isoborneol has been used in the treatment of cardiovascular disease for several years in China. However, the mechanism is still unclear. The aim of this study was to identify the novel mechanism of isoborneol for its application in atherosclerotic disease. Materials and Methods: The whole-genome gene expression profiles of MCF-7 cells treated with/or without isoborneol were detected by mRNA microarray analysis. The degree of similarity between the gene expression profiles was compared with the Connectivity Map (CMAP) database. An MTT assay was used to assess the toxicity of isoborneol on RAW 264.7 cells. Oil red O staining and a Dil-ox-LDL uptake assay in RAW 264.7 cells were also used to detect the accumulation of lipids in the macrophages and the uptake of oxidized lowdensity lipoprotein (ox-LDL). Results: Isoborneol was proved to have mRNA expression profiles similar to that of ikarugamycin which can inhibit the uptake of ox-LDL. This process has proved to be an important cause of foam cell formation and early atherosclerotic lesions. It is speculated, therefore, that isoborneol may show similar activity to that shown by ikarugamycin. Subsequently, it was shown that RAW 264.7 cells reduced the absorption of ox-LDL and the accumulation of intracellular lipids after treatment with different concentrations of isoborneol. Conclusion: The results indicate that isoborneol inhibits macrophage consumption of ox-LDL, thereby preventing the accumulation of lipids in the macrophages. These results provide evidence for the application of isoborneol in atherosclerotic disease.

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Curcumin Equipped Nanozyme‐Like Metal−Organic Framework Platform for the Targeted Atherosclerosis Treatment with Lipid Regulation and Enhanced Magnetic Resonance Imaging Capability

Lv,

Fang,

Huang

et al. 2024

Advanced Science

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Atherosclerotic cardiovascular disease (ASCVD) has become the leading cause of death worldwide, and early diagnosis and treatment of atherosclerosis (AS) are crucial for reducing the occurrence of acute cardiovascular events. However, early diagnosis of AS is challenging, and oral anti‐AS drugs suffer from limitations like imprecise targeting and low bioavailability. To overcome the aforementioned shortcomings, Cur/MOF@DS is developed, a nanoplatform integrating diagnosis and treatment by loading curcumin (Cur) into metal−organic frameworks with nanozymes and magnetic resonance imaging (MRI) properties. In addition, the surface‐modification of dextran sulfate (DS) enables PCN‐222(Mn) effectively target scavenger receptor class A in macrophages or foam cells within the plaque region. This nanoplatform employs mechanisms that effectively scavenge excessive reactive oxygen species in the plaque microenvironment, promote macrophage autophagy and regulate macrophage polarization to realize lipid regulation. In vivo and in vitro experiments confirm that this nanoplatform has outstanding MRI performance and anti‐AS effects, which may provide a new option for early diagnosis and treatment of AS.

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Targeting Foam Cell Formation in Atherosclerosis: Therapeutic Potential of Natural Products

Cited by 124 publications

References 885 publications

Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

<p>Isoborneol Attenuates Low-Density Lipoprotein Accumulation and Foam Cell Formation in Macrophages</p>

Curcumin Equipped Nanozyme‐Like Metal−Organic Framework Platform for the Targeted Atherosclerosis Treatment with Lipid Regulation and Enhanced Magnetic Resonance Imaging Capability

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