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Pulmonary alveolar proteinosis (PAP) is a life-threatening, rare lung syndrome for which there is no cure and no approved therapies. PAP is a disease of lipid accumulation characterized by alveolar macrophage foam cell formation. While much is known about the clinical presentation, there is a paucity of information regarding temporal changes in lipids throughout the course of disease. Our objectives were to define the detailed lipid composition of alveolar macrophages in PAP patients at the time of diagnosis and during treatment. We performed comprehensive mass spectrometry to profile the lipid signature of alveolar macrophages obtained from three independent mouse models of PAP and from PAP and non-PAP patients. Additionally, we quantified changes in macrophage-associated lipids during clinical treatment of PAP patients. We found remarkable variations in lipid composition in PAP patients, which were consistent with data from three independent mouse models. Detailed lipidomic analysis revealed that the overall alveolar macrophage lipid burden inversely correlated with clinical improvement and response to therapy in PAP patients. Specifically, as PAP patients experienced clinical improvement, there was a notable decrease in the total lipid content of alveolar macrophages. This crucial observation suggests that the levels of these macrophage-associated lipids can be utilized to assess the efficacy of treatment. These findings provide valuable insights into the dysregulated lipid metabolism associated with PAP, offering the potential for lipid profiling to serve as a means of monitoring therapeutic interventions in PAP patients.

This article discusses the experimental investigation of the dynamic mechanical behavior of polyethylene (PE) foam under shock wave loading. The experiments were conducted using a two-stage light shock tube, and the dynamic response of the foam was characterized by measuring the pressure wave transmitted through the foam and the load on the foam specimen using a pressure sensor and a load cell, respectively. High-speed imaging was also used to capture the deformation of the foam specimen during the shock loading. The results show that the deformation of the foam under shock wave loading is non-uniform along the length of the specimen and is influenced by the presence of metal plates inserted along the length of the foam specimen. The degree of compression of the foam specimen was quantified and found to depend on the number of segments and the presence of metal caps on the specimen. The results provide insight into the mechanical behavior of PE foam under dynamic loading conditions and can be useful for designing protective structures for impact and blast resistance applications. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis is an arterial blood vessel disease that begins and progresses by turning macrophages into foam cells. Uptake of oxidized low-density lipoprotein (ox-LDL), cholesterol esterification and cholesterol efflux are the most important factors in the formation of foam cells and play an important role in atherosclerosis. Methods: The present study is based on the data obtained from the PubMed database (1961–2024) using the MeSH search terms "Atherosclerosis", "Macrophages" and "Foam cells". Reviews for writing the main text and non-English-language articles were excluded. Result: The interaction between ox-LDL and macrophages plays an important role in plaque initiation and promotion processes. Macrophages abnormally digest ox-LDL, resulting in the accumulation of lipids and formation of foam cells. This is an important step in the development of atherosclerosis. Also, several other factors such as inflammatory factors, growth factors, hormones, etc. can play an important role in the development of atherosclerotic lesions or counteract it by affecting the formation of foam cells. Conclusion: Several factors can affect the progression of atherosclerosis by affecting macrophage activity or its conversion to foam cells. Also, some of these factors play a protective role against the development and atherosclerosis progression. In this paper, we reviewed some of these factors and their effect on atherosclerosis. Highlights: Foam cell formation plays an important role in the initiation and progression of atherosclerosis. Absorption ox-LDL, cholesterol esterification and cholesterol efflux cause foam cell formation. Intracellular free cholesterol is increased by ox-LDL uptake via scavenger receptors, leading to foam cell production. Some factors can play a dual stimulus-inhibitory role in foam cell formation. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory disease that poses a serious threat to human health. It starts with the buildup of plaque in the artery wall, which results from the accumulation of pro‐inflammatory factors and other substances. In this paper, we propose a mathematical model of early atherosclerosis with a free boundary and time delay. The time delay represents the time required for macrophages to transit to foam cells through cholesterol accumulation. We obtain an explicit solution and analyze the stability of the model and the effect of the time delay on plaque size. We show that in the form of perturbation cos(nθ)$$ \cos \left(n\theta \right) $$ (where n$$ n $$ represents the mode of angle), when n=0$$ n=0 $$ or 1, the steady‐state solution (M∗,p∗,r∗)$$ \left({M}_{\ast },{p}_{\ast },{r}_{\ast}\right) $$ is linearly stable; when n≥2$$ n\ge 2 $$, there exists a critical parameter L∗$$ {L}_{\ast } $$ such that the steady‐state solution is linearly stable for LL∗$$ L>{L}_{\ast } $$. Moreover, we find that smaller plaque are associated with the presence of time delay. [ABSTRACT FROM AUTHOR]

Background and purpose: Atherosclerosis is the basis of cardiovascular disease. Ferroptosis is a form of programmed cell death characterized by lipid peroxidation, which contributes to atherogenesis. The plant extract PNS (Panax notoginseng saponins), containing the main active ingredients of Panax notoginseng, exhibits anti‐atherogenic properties. Herein, we determined whether PNS and its major components could attenuate atherosclerosis by suppressing ferroptosis and revealed the underlying mechanism(s). Experimental approach: The anti‐atherogenic effects of PNS and their association with inhibition of ferroptosis was determined in apoE−/− mice. In vitro, the anti‐ferroptotic effect and mechanism(s) of PNS components were demonstrated in the presence of ferroptosis inducers. Expression of ferroptosis markers and the ubiquitination of Keap1 were evaluated in USP2−/− macrophages. Finally, the anti‐atherogenic effect of USP2 knockout was determined by using USP2−/− mice treated with high‐fat diet (HFD) and AAV‐PCSK9. Key results: PNS inhibited ferroptosis and atherosclerosis in vivo. PNS suppressed ferroptosis and ferroptosis‐aggravated foam cell formation and inflammation in vitro. Mechanistically, PNS and its components activated Nrf2 by antagonizing Keap1, which was attributed to the inhibition of USP2 expression. USP2 knockout antagonized ferroptosis and ferroptosis‐aggravated foam cell formation and inflammation, thus mitigating atherosclerosis. USP2 knockout abolished inhibitory effects of PNS on foam cell formation and inflammation in vitro. Conclusion and implications: PNS reduced USP2‐mediated Keap1 de‐ubiquitination and promoted Keap1 degradation, thereby activating Nrf2, improving iron metabolism and reducing lipid peroxidation, thus contributing to an anti‐atherosclerotic outcome. Our study revealed the mechanism(s) underlying inhibition of ferroptosis and atherosclerosis by PNS. [ABSTRACT FROM AUTHOR]

Background: At present, fat transplantation is widely used in the plastic surgery industry, but the long-term preservation rate of transplanted fat decreases because of complications such as oil cysts due to the inability in macrophages to metabolize absorption. In cell-assisted lipotransfer technology, adipose-derived stem cells (ASCs) can influence the inflammatory response of grafts through the immunoregulation in macrophages, and the lipid metabolism in macrophages plays an important role in this process. Therefore, we hypothesized ASCs could improve the retention rate of fat grafts by regulating the progress of lipid metabolism in macrophages. Methods: We established fat transplantation and ASC-assisted fat transplantation model in C57BL/6 mice in vivo, and bone marrow-derived macrophages cocultured with apoptotic adipocytes were treated with or without ASCs in vitro. Graft retention, tissue structure, fibrosis, macrophage phenotype transformation, lipid deposition, mitochondrial morphology, oxygen consumption rate (OCR), fatty acid β-oxidation (FAO) level, and ATP production were assessed. Additionally, fat transplantation and ASC-assisted fat transplantation model was treated with etomoxir which inhibits mitochondrial FAO. Macrophages pretreated with etomoxir were co-cultured with apoptotic adipocytes and treated with or without ASCs. The method aboved was used for detection and verification. Results: In vivo, ASC-assisted fat transplantation improved macrophage mitochondrial expression and FAO level, promoted the early transformation of M2 macrophages, reduced the long-term lipid deposition of macrophages, and improved the retention rate of fat grafts. In vitro, ASCs up-regulated the level of mitochondrial FAO, OCR and ATP production in macrophages, reduced lipid deposition of macrophages and promoted M2 macrophages polarization by paracine function. The ability of ASCs in group pretreated with etomoxir to reduce the foaming of macrophages, promote the transformation to M2 macrophages, and improve the retention rate of fat transplantation was weakened. Conclusions: ASCs increased the retention rate of transplanted fat by upregulating mitochondrial FAO to promote M2 polaration in macrophages. In addition, ASCs up-regulate mitochondrial FAO by paracrine effect to reduce foam cells formation and promote M2 transformation in macrophages in vitro. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is the leading cause of coronary heart disease, which is the primary cause of death worldwide. Recent studies have identified disulfidptosis as a new type of cell death that may be involved in onset and development of many diseases. However, the role of disulfidptosis in AS is not clear. In this study, bioinformatics analysis and experiments in vivo and in vitro were performed to evaluate the potential relationship between disulfidptosis and AS. AS-related sequencing data were obtained from the Gene Expression Omnibus (GEO). Bioinformatics techniques were used to evaluate differentially expressed genes (DEGs) associated with disulfidptosis-related AS. Hub genes were screened using least absolute shrinkage and selection operator (LASSO) and random forests (RF) methods. In addition, we established a foam cell model in vitro and an AS mouse model in vivo to verify the expressions of hub genes. In addition, we constructed a diagnostic nomogram with hub genes to predict progression of AS. Finally, the consensus clustering method was used to establish two different subtypes, and associations between subtypes and immunity were explored. As the results, 9 disulfidptosis-related AS DEGs were identified from GSE28829 and GSE43292 datasets. Evaluation of DEGs using LASSO and RF methods resulted in identification of 4 hub genes (CAPZB, DSTN, MYL6, PDLIM1), which were analyzed for diagnostic value using ROC curve analysis and verified in vitro and in vivo. Furthermore, a nomogram including hub genes was established that accurately predicted the occurrence of AS. The consensus clustering algorithm was used to separate patients with early atherosclerotic plaques and patients with advanced atherosclerotic plaques into two disulfidptosis subtypes. Cluster B displayed higher levels of infiltrating immune cells, which indicated that patients in cluster B may have a positive immune response for progression of AS. In summary, disulfidptosis-related genes including CAPZB, DSTN, MYL6, and PDLIM1 may be diagnostic markers and therapeutic targets for AS. In addition, these genes are closely related to immune cells, which may inform immunotherapy for AS. [ABSTRACT FROM AUTHOR]

Excess cholesterol accumulation induces the accumulation of foam cells, eventually accelerating atherosclerosis progress. Historically, the mechanisms of macrophage-derived foam cells have attracted attention because of their central role in plaque development, which was challenged by lineage tracing in union with single-cell sequencing (sc-seq). Accumulated studies have uncovered how vascular smooth muscle cells (VSMCs) proliferate and migrate to the vascular intima and accumulate, then transform into foam cells induced by surplus lipids, finally accounting for 30% to 70% of the total foam cells within the plaque of both mice and humans. Therefore, the mechanisms of VSMC-derived foam cells have received increasing attention. The review intends to summarize the transformation mechanism of VSMCs into foam cells induced by oxidized low-density lipoproteins (ox-LDL) in atherosclerosis. [ABSTRACT FROM AUTHOR]

This review focuses on the epigenetic factors that play a vital role in the formation of plaques and lead to atherosclerosis and related diseases in humans during current times. Apart from the epigenetics there are plenty more factors that influence the atherosclerotic risk in the older population of the current era. Lack of physical activities has become one of the most commonly found traits that causes obesity in people especially the middles aged adults. People working 9 - 5 in an office, or an IT firm tend spend idle time with their computer for 4 - 5 consecutive hours with barely changing their position. Lack of exercise tends to affect not only the physical health but also stress a person mentally. Chronic inflammatory diseases like atherosclerosis have a major role in the morbidity and mortality from cardiovascular disease worldwide. Atherosclerotic plaques are created by the pathophysiological process of lipids, inflammatory cells and fibrous components gradually accumulating within artery walls. Endothelial dysfunction signals the start of atherosclerosis and allows low-density lipoproteins (LDL) to enter the subendothelial region. Oxidative stress-induced changes in retained low-density lipoprotein (LDL) set off an inflammatory cascade that draws T cells and monocytes to the site of the lesion. The interaction of these immune cells with the local vascular cells encourages the production of foam cells, which fills the plaque's centre with lipids. Smooth muscle cells multiply and help produce fibrous caps as the lesion ages, which affects the stability of the plaque. Studies shows how the brain responds to physical labour and how differently the effectively the enzymes and hormones are secreted, and their actions are vastly guided based on the physical stress an individual undergoes. Among the most prominent causes of atherosclerosis epigenetics has been focused majorly in this review, where we focus on the underlying genetic factors that play a vital role in atherosclerosis and related cardiovascular diseases and also the genetic approach to a treatment is also elaborated. A number of miRNAs are involved in the cause/cure for the atherosclerosis, the following tables give an outlook regarding the same. This review aims to focus on the causes, risk factors, pathophysiology and the treatment and therapies that are currently available all the way concentrating on the genetic approach in the above-mentioned perspective. [ABSTRACT FROM AUTHOR]

This paper presents the novel development of a shape memory polymer foam based on polymer–polymer nanocomposites. Herein, polylactide (PLA)/biosourced polyamide (PA) foams are fabricated by in situ fibrillation of polymer blends and a subsequent supercritical CO2 foaming technique. In this system, PLA serves as a shape memory polymer to endow this foam with a shape memory effect (SME), and in situ generated PA nanofibers are employed to reinforce the PLA cell walls and provide an additional permanent phase. A concentration of PA, 5 wt.%, was chosen to form an entangled nanofibrillar network. Foams of PLA/PA nanoblends with the same content of constituents were fabricated to reveal the effect of minor phase morphology on the cell structure and shape memory behavior of polymer foams. Profiting from the reinforcing effect of PA nanofibers, the PLA/PA nanocomposite foam exhibits smaller foam cells, a narrower cell size distribution and a comparable cell concentration than the PLA/PA nanoblend foam. In addition, PA nanofibers, unlike PA nanodroplets, favor the shape fixation ratio and recovery ratio and shorten the shape recovery time. [ABSTRACT FROM AUTHOR]

Modified cholesterols such as oxidized low-density lipoprotein (OxLDL) contribute to atherosclerosis and other disorders through the promotion of foam cell formation and inflammation. In recent years, it has become evident that immune cell responses to inflammatory molecules such as OxLDLs depend on cellular metabolic functions. This review examines the known effects of OxLDL on immunometabolism and immune cell responses in atherosclerosis and several other diseases. We additionally provide context on the relationship between OxLDL and aging/senescence and identify gaps in the literature and our current understanding in these areas. [ABSTRACT FROM AUTHOR]

Incretin receptor agonists (IRAs), primarily composed of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and glucose-dependent insulinotropic polypeptide receptor agonists (GIPRAs), work by mimicking the actions of the endogenous incretin hormones in the body. GLP-1RAs have been approved for use as monotherapy and in combination with GIPRAs for the management of type 2 diabetes mellitus (T2DM). In addition to their role in glucose regulation, IRAs have demonstrated various benefits such as cardiovascular protection, obesity management, and regulation of bone turnover. Some studies have suggested that IRAs not only aid in glycemic control but also exhibit anti-atherosclerotic effects. These agents have been shown to modulate lipid abnormalities, reduce blood pressure, and preserve the structural and functional integrity of the endothelium. Furthermore, IRAs have the ability to mitigate inflammation by inhibiting macrophage activation and promoting M2 polarization. Research has also indicated that IRAs can decrease macrophage foam cell formation and prevent vascular smooth muscle cell (VSMC) phenotype switching, which are pivotal in atheromatous plaque formation and stability. This review offers a comprehensive overview of the protective effects of IRAs in atherosclerotic disease, with a focus on their impact on atherogenesis. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) poses a significant threat to human life and health. However, conventional antiatherogenic medications exhibit insufficient targeting precision and restricted therapeutic effectiveness. Moreover, during the progression of AS, macrophages undergo polarization toward the proinflammatory M1 phenotype and generate reactive oxygen species (ROS) to accelerate the occurrence of inflammatory storms, and ingest excess lipids to form foam cells by inhibiting cholesterol efflux. In our study, we developed a macrophage membrane-functionalized hollow mesoporous manganese dioxide nanomedicine (Col@HMnO2-MM). This nanomedicine has the ability to evade immune cell phagocytosis, enables prolonged circulation within the body, targets the inflammatory site of AS for effective drug release, and alleviates the inflammatory storm at the AS site by eliminating ROS. Furthermore, Col@HMnO2-MM has the ability to generate oxygen autonomously by breaking down surplus hydrogen peroxide generated at the inflammatory AS site, thereby reducing the hypoxic microenvironment of the plaque by downregulating hypoxia-inducible factor (HIF-1α), which in turn enhances cholesterol efflux to inhibit foam cell formation. In an APOE−/− mouse model, Col@HMnO2-MM significantly reduced inflammatory factor levels, lipid storage, and plaque formation without significant long-term toxicity. In summary, this synergistic treatment significantly improved the effectiveness of nanomedicine and may offer a novel strategy for precise AS therapy. [ABSTRACT FROM AUTHOR]

Current diagnostic technique in direct identification of multi‐site plaques and simultaneous assessment of plaque vulnerability remains a challenge, which is crucial for indicating the risk of atherosclerotic cardiovascular diseases (ASCVD). Herein, an osteopontin (OPN)‐specific nanoprobe (OPN Ab‐Au/FeNiPO4@ICG) with both multiple spectra optoacoustic tomography (MSOT) and computed tomography (CT) imaging, is constructed successfully realizing systemic screening of vulnerable plaque. OPN Ab‐Au/FeNiPO4@ICG nanoprobe specifically targeted OPN‐overexpressed foam cells and recognized the vulnerable plaque at the molecular level. In AS mice, CT imaging exhibits that OPN Ab‐Au/FeNiPO4@ICG nanoprobe effectively avoid interference from calcification and accurately visualized AS plaque. MSOT functional imaging results reveals that after the injection of OPN Ab‐Au/FeNiPO4@ICG nanoprobe, the carotid plaque exhibited a much higher MSOT signal than the aortic arch plaque (P = 0.0291). Further pathological analysis displays that the carotid plaque possessed a much higher vulnerability score (P = 0.0247), in agreement with the MSOT signals. More importantly, the linear regression analysis confirms the high correlation between the MSOT signals and plaque vulnerability with R = 0.7095 (P = 0.0216), demonstrating the potential of the proposed nanoprobe in systematic evaluation of plaque vulnerability. This work employs the dual‐model nanoprobe strategy for both plaque localization and vulnerability assessment, greatly advancing the accurate diagnosis of ASCVD. [ABSTRACT FROM AUTHOR]

Glioblastoma presents a formidable clinical challenge because of its complex microenvironment. Here, we characterized tumor-associated foam cells (TAFs), a type of lipid droplet--loaded macrophage, in human glioblastoma. Through extensive analyses of patient tumors, together with in vitro and in vivo investigations, we found that TAFs exhibit distinct protumorigenic characteristics related to hypoxia, mesenchymal transition, angiogenesis, and impaired phagocytosis, and their presence correlates with worse outcomes for patients with glioma. We further demonstrated that TAF formation is facilitated by lipid scavenging from extracellular vesicles released by glioblastoma cells. We found that targeting key enzymes involved in lipid droplet formation, such as diacylglycerol O-acyltransferase or long- chain acyl- CoA synthetase, effectively disrupted TAF functionality. Together, these data highlight TAFs as a prominent immune cell population in glioblastoma and provide insights into their contribution to the tumor microenvironment. Disrupting lipid droplet formation to target TAFs may represent an avenue for future therapeutic development for glioblastoma. [ABSTRACT FROM AUTHOR]

Osteomyelitis occurs when Staphylococcus aureus invades the bone microenvironment, resulting in a bone marrow abscess with a spatially defined architecture of cells and biomolecules. Imaging mass spectrometry and microscopy are tools that can be employed to interrogate the lipidome of S. aureus -infected murine femurs and reveal metabolic and signaling consequences of infection. Here, nearly 250 lipids were spatially mapped to healthy and infection-associated morphological features throughout the femur, establishing composition profiles for tissue types. Ether lipids and arachidonoyl lipids were altered between cells and tissue structures in abscesses, suggesting their roles in abscess formation and inflammatory signaling. Sterols, triglycerides, bis(monoacylglycero)phosphates, and gangliosides possessed ring-like distributions throughout the abscess, suggesting a hypothesized dysregulation of lipid metabolism in a population of cells that cannot be discerned with traditional microscopy. These data provide insight into the signaling function and metabolism of cells in the fibrotic border of abscesses, likely characteristic of lipid-laden macrophages. [Display omitted] • Lipids are spatially mapped to tissue types throughout an S. aureus -infected femur • Multimodal MALDI IMS uncovers lipid dynamics between bacteria and leukocytes • Molecular phenotyping suggests lipid-laden macrophages in a bone marrow abscess Good et al. present lipidomics data directly acquired from infected murine femurs, providing a unique insight into the molecular and cellular environment driving the complex pathology of bone infections. This multimodal molecular imaging approach is valuable for understanding the mechanisms by which S. aureus evades immune clearance in bone tissue. [ABSTRACT FROM AUTHOR]

This study aimed to enhance the melt strength, foamability, and microstructural properties of poly(ethylene terephthalate) (PET) foam by addition of styrene maleic anhydride (SMA) as a chain extender. The addition of SMA to the polymer increased the complex viscosity by 375%. The calculated dissipation factor for chain‐extended‐PET (CE‐PET) samples demonstrated a rise in polymer viscous behavior with increasing SMA content. The CE‐PET was more elastic than pure PET. Smaller oval‐shaped cells were produced with lower amounts of foaming agent/SMA, whereas higher ratios resulted in larger spree‐shaped cells. The reaction of SMA anhydrides with the end functional groups of the PET chains increased the chain length significantly followed by more entanglement. This behavior prevented cell growth during the foaming process. The confrontation between the physical and chemical forces among the PET chains and the gas pressure created by the foaming agent was the main mechanism of cell growth in the polymer matrix. This variation caused a 30% reduction in foam density. Statistical analysis revealed that CE‐PET foams with the largest cell size and lowest density were achieved with foaming agent amounts between 0.9 and 1.4 wt.% and SMA amounts between 4.7 and 7.3 wt.%. [ABSTRACT FROM AUTHOR]

Atherosclerosis, a chronic inflammatory cardiovascular disease, leads to arterial constriction caused by the accumulation of lipids, cholesterol, and various substances within artery walls. Such plaque can rupture, resulting in a blood clot that obstructs major arteries and may initiate myocardial infarction, ischemic stroke, etc. Atherosclerotic plaque formation begins with the accumulation of foam cells and macrophages within the intima layer of the arterial wall. At the latter stage, the smooth muscle cells migrated from deeper artery wall layers, contributing to the fibrous cap formation and plaque stabilizing. A developed plaque gradually enters the lumen and narrows down the lumen to impede blood flow. We introduce a two-phase and macroscopic model to investigate the progression of plaque growth in its advanced stage and analyze the minimum gap (Lumen Clearance) within an atherosclerotic artery so that blood cells can pass through. Cardiac troponin, a high specificity and sensitivity biomarker, facilitates early detection of elevated myocardial infarction, ischemic stroke risks, etc. This study aims at establishing a relationship between the troponin concentration in atherosclerotic arteries and their internal clearance, which could significantly improve our understanding of disease progression. Our observations show that the plaque undergoes rapid evolution in its initial stages, gradually slowing down over time to reach a stable state. A positive correlation exists between the maximum plaque depth and cardiac troponin concentration in the blood. However, the lumen clearance exhibits the opposite behavior. The speed of blood cells slows down at an enhanced plaque depth within atherosclerotic arteries. [ABSTRACT FROM AUTHOR]

Introduction: Atherosclerosis is a chronic inflammatory condition characterized by arterial foam cell accumulation. In mice, MNV-infected macrophages develop atherosclerotic lesions. Due to MNV-3's affinity for macrophages expressing CD36, CD88, and CD11b, we examined its influence on these markers. Materials and methods: Recombinant MNV-3 was recovered using a DNA-based recovery system as described previously. The third passage of MNV-3 was used to infect RAW 264.7 cells at MOI of 0.5 followed by treatment with 80µg/ml of oxLDL and samples were collected 24 hours post-treatment for various assays. Verification of MNV-3 infection was achieved through PCR, TCID50, and Western blotting analyses. The ORO staining and TCE assays were used to assess lipid droplets and total cholesterol content. The FACS and qRT-PCR assays were carried out to measure CD36, CD88, and CD11b cell surface proteins and mRNA expression levels. ELISA analysis quantified the IL-ß, TNF-a, TGF-ß, and IL-6 secretion levels. Results: MNV-3 infection in RAW 264.7 cells was confirmed by PCR with a 342bp amplicon targeting the viral subgenomic region. OxLDL inhibited MNV-3 replication in RAW 264.7 cells. Combining MNV-3 with oxLDL significantly decreases RAW 264.7 CD36, CD88, and CD11b surface protein expression. This treatment regime also significantly reduced the CD36 and CD88 transcript levels. MNV-3 with oxLDL significantly reduced IL-1ß, IL-6, and TNF-a secretion whilst TGF-ß was significantly increased. Conclusion: Combining MNV-3 with oxLDL reduced cholesterol and lipid droplets by decreasing CD36, CD88, and CD11b, reducing L-1ß, IL-6, and TNF-a secretions, and enhancing TGF-ß secretion. The study suggests that MNV-3 infection exhibits anti-atherogenic effects, potentially offering biomedical implications. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation and foam cell formation in the arterial wall. Promoting macrophage autophagy has emerged as a promising therapeutic strategy against atherosclerosis. Dipsacoside B (DB) is an oleanane-type pentacyclic triterpenoid saponin extracted from Lonicerae flos with potential anti-atherosclerotic properties. In this study, we investigated the effects of DB on atherosclerosis progression in ApoE−/− mice fed a high-fat diet and explored the underlying mechanisms in oxidized low-density lipoprotein (ox-LDL)-induced foam cells. DB treatment significantly reduced atherosclerotic lesion size, improved plaque stability, and regulated lipid metabolism without impairing liver and kidney function in ApoE−/− mice. In vitro studies revealed that DB dose-dependently inhibited ox-LDL internalization and intracellular lipid accumulation in RAW264.7 macrophages. Mechanistically, DB induced autophagy, as evidenced by increased autophagosome formation and upregulated expression of autophagy markers LC3-II and p62 both in vivo and in vitro. Inhibition of autophagy by chloroquine abolished the antiatherosclerotic and pro-autophagic effects of DB. Furthermore, DB treatment increased LC3-II and p62 mRNA levels, suggesting transcriptional regulation of autophagy. Collectively, our findings demonstrate that DB exerts anti-atherosclerotic effects by inhibiting foam cell formation via autophagy induction, providing new insights into the pharmacological actions of DB and its potential as a therapeutic agent against atherosclerosis. [ABSTRACT FROM AUTHOR]

This letter discusses a case report of a 47-year-old female patient with Xanthogranulomatous pyelonephritis (XGP), a rare and chronic inflammation of the renal parenchyma. The patient had a history of nephrolithiasis, chronic lumbago, and recurrent urinary tract infections. The diagnosis of XGP was suspected based on physical examination, imaging, and laboratory analysis, and confirmed through histopathological examination and urinary foam cell detection. The patient underwent percutaneous nephrolithotomy and drainage as treatment. The letter emphasizes the importance of urine foam cell examination for preoperative diagnosis and kidney-sparing treatment guidelines for XGP. [Extracted from the article]

Nowadays, cardiovascular diseases are the most common cause of death worldwide. Besides, atherosclerosis is a cardiovascular disease that occurs with persistent narrowing of arteries, especially medium and large-sized arteries. Atherosclerosis begins with a local elevation in the permeability of the arterial wall as a result of endothelial inflammation. Subsequently, excess LDL permeates into the arterial wall. Then, through several chemical responses and reactions, foam cells are produced. These foam cells serve as a crucial indicator for assessing the development of atherosclerosis within the arteries. In this study, the effect of endothelial layer modeling, heart rate (HR) and hypertension on the foam cell accumulation is numerically investigated in a patient-specific geometry of the human thoracic aorta. Navier–Stokes, Darcy, and mass transfer equations are used to obtain the velocity and concentration field within the domain. Regarding the dependence of endothelial cell properties on time-averaged wall shear stress, it is observed that foam cells are mainly concentrated in the outer curvature of the aortic arch, downstream of the left subclavian artery. However, considering oscillatory-shear-rate as the determinant of endothelial cell properties leads to the accumulation of foam cells in the inner curvature of the descending aorta. Regarding the HR, with the increase of HR, the volume average concentration of the foam cell decreases. However, there is no substantial difference between the cases of different HRs. Moreover, foam cell concentration significantly increases in the hypertension case. This result implies that a slight increase in the blood pressure may induce irreparable problems in the circulatory system. [ABSTRACT FROM AUTHOR]

In [3] a mathematical model of the initiation and development of atherosclerosis involving LDL and HDL cholesterol, macrophages, and foam cells was introduced. The model is a highly nonlinear and coupled system of PDEs with a free boundary – the interface between the plaque and the blood flow. We establish infinite branches of symmetry-breaking stationary solutions that bifurcate from the stationary annular solution in the combined longitude-latitude direction. After establishing various estimates for our PDE system, the Crandall-Rabinowitz theorem is applied to prove our main bifurcation theorem. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory disease characterized by the gradual formation of plaques due to lipid deposition on the inner walls of blood vessels, which can lead to narrowing, blockage, or rupture of the arteries, posing a significant risk to cardiovascular health. In this study, we study the bifurcation of a highly nonlinear and coupled model describing the early growth of atherosclerotic plaques with Holling type III functional response, involving low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, cytokines, pro-inflammatory macrophages, anti-inflammatory macrophages, and foam cells, with a free boundary separating the plaque from the blood flow region. We first prove the existence and uniqueness of radially symmetric steady-state solutions, and then establish a finite branch of symmetry-breaking steady-state solutions from the radially symmetric ones. This result helps us to understand the reason of plaque asymmetry in real life. [ABSTRACT FROM AUTHOR]

Abstract Benign prostatic hyperplasia (BPH) is a prevalent age-related condition often characterized by debilitating urinary symptoms. Its etiology is believed to stem from hormonal imbalance, particularly an elevated estradiol-to-testosterone ratio and chronic inflammation. Our previous studies using a mouse steroid hormone imbalance model identified a specific increase in macrophages that migrated and accumulated in the prostate lumen where they differentiated into lipid-laden foam cells in mice implanted with testosterone and estradiol pellets, but not in sham animals. The current study focused on further characterizing the cellular heterogeneity of the prostate in this model as well as identifying the specific transcriptomic signature of the recruited foam cells. Moreover, we aimed to identify epithelia-derived signals that drive macrophage infiltration and luminal translocation. Male C57BL/6J mice were implanted with slow-release testosterone and estradiol pellets (T + E2) or sham surgery was performed and the ventral prostates were harvested two weeks later for scRNA-seq analysis. We identified Ear2 + and Cd72 + macrophages that were elevated in response to steroid hormone imbalance, whereas a Mrc1 + resident macrophage population did not change. In addition, an Spp1 + foam cell cluster was almost exclusively found in T + E2 mice. Further markers of foam cells were also identified, including Gpnmb and Trem2, and GPNMB was confirmed as a novel histological marker with immunohistochemistry. Foam cells were also shown to express known pathological factors Vegf, Tgfb1, Ccl6, Cxcl16 and Mmp12. Intriguingly, a screen for chemokines identified the upregulation of epithelia-derived Cxcl17, a known monocyte attractant, in T + E2 prostates suggesting that it might be responsible for the elevated macrophage number as well as their translocation to the lumen. Our study identified macrophage subsets that responded to steroid hormone imbalance as well as further confirmed a potential pathological role of luminal foam cells in the prostate. These results underscore a potential pathological role of the identified prostate foam cells and suggests CXCL17-mediated macrophage migration as a critical initiating event.

Microcellular injection molding (MuCell®) using supercritical fluid (SCF) as a foaming agent to achieve weight reduction has become popular in carbon emission reduction. In the typical MuCell® process, SCF N2 is commonly used. Although SCF CO2 exhibits high solubility and can achieve a high weight reduction, controlling the foaming is not easy, and its foaming cells are usually larger and less uniform, which limits its industrial application. Our previous studies have shown that gas counter pressure (GCP) can improve the foaming quality effectively. Here, we investigated whether or not the CO2 SCF foaming quality could be improved, and weight reduction was achieved for polycarbonate (PC) material. This is quite important for the electronics industry, in which most of the housing for devices is made of PC materials. MuCell® was subjected to molding experiments using the parameters of the SCF dosage, melt temperature, mold temperature, and injection speed. The results revealed that using CO2 gas for the PC material can reduce the size of microcellular cells to 40 µm and increase the cell densities to 3.97 × 106 cells/cm3. Using GCP significantly improved the microcellular injection-molded parts by reducing the cell size to 20.9 µm (a 45.41% improvement) and increasing the cell density to 8.04 × 106 cells/cm3 (a 102.48% improvement). However, implementing GCP may slightly decrease the target weight reduction. This study reveals that microcellular injection molding of PC parts using SCF CO2 can achieve high-quality foaming and reduce the weight by about 30%. [ABSTRACT FROM AUTHOR]

Background: Capsaicin, a bioactive compound found in peppers, is recognized for its anti-inflammatory, antioxidant, and anti-lipidemic properties. This study aimed to evaluate the effects of capsaicin on atherosclerosis progression. Methods: Apolipoprotein E knockout mice and their C57BL/6 controls were utilized to assess blood lipid profile, inflammatory status, and atherosclerotic lesions. We also examined the influence of capsaicin on cholesterol influx and efflux, and the role of TRPV1 and PPARγ signaling pathways in bone marrow-derived macrophages. Results: Capsaicin treatment reduced weight gain, visceral adiposity, blood triglycerides, and total and non-HDL cholesterol. These improvements were associated with a reduction in atherosclerotic lesions in the aorta and carotid. Capsaicin also improved hepatic oxidative and inflammatory status. Systemic inflammation was also reduced, as indicated by reduced leukocyte rolling and adhesion on the mesenteric plexus. Capsaicin decreased foam cell formation by reducing cholesterol influx through scavenger receptor A and increasing cholesterol efflux via ATP-binding cassette transporter A1, an effect primarily linked to TRPV1 activation. Conclusions: These findings underscore the potential of capsaicin as a promising agent for atherosclerosis prevention, highlighting its comprehensive role in modulating lipid metabolism, foam cell formation, and inflammatory responses. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH) is a prevalent age-related condition often characterized by debilitating urinary symptoms. Its etiology is believed to stem from hormonal imbalance, particularly an elevated estradiol-to-testosterone ratio and chronic inflammation. Our previous studies using a mouse steroid hormone imbalance model identified a specific increase in macrophages that migrated and accumulated in the prostate lumen where they differentiated into lipid-laden foam cells in mice implanted with testosterone and estradiol pellets, but not in sham animals. The current study focused on further characterizing the cellular heterogeneity of the prostate in this model as well as identifying the specific transcriptomic signature of the recruited foam cells. Moreover, we aimed to identify epithelia-derived signals that drive macrophage infiltration and luminal translocation. Male C57BL/6J mice were implanted with slow-release testosterone and estradiol pellets (T + E2) or sham surgery was performed and the ventral prostates were harvested two weeks later for scRNA-seq analysis. We identified Ear2 + and Cd72 + macrophages that were elevated in response to steroid hormone imbalance, whereas a Mrc1 + resident macrophage population did not change. In addition, an Spp1 + foam cell cluster was almost exclusively found in T + E2 mice. Further markers of foam cells were also identified, including Gpnmb and Trem2, and GPNMB was confirmed as a novel histological marker with immunohistochemistry. Foam cells were also shown to express known pathological factors Vegf, Tgfb1, Ccl6, Cxcl16 and Mmp12. Intriguingly, a screen for chemokines identified the upregulation of epithelia-derived Cxcl17, a known monocyte attractant, in T + E2 prostates suggesting that it might be responsible for the elevated macrophage number as well as their translocation to the lumen. Our study identified macrophage subsets that responded to steroid hormone imbalance as well as further confirmed a potential pathological role of luminal foam cells in the prostate. These results underscore a potential pathological role of the identified prostate foam cells and suggests CXCL17-mediated macrophage migration as a critical initiating event. [ABSTRACT FROM AUTHOR]

Background: Chrysin, a polyphenolic compound, possesses antioxidant and anti-inflammatory properties. In this study, we investigated the effect of chrysin on the expression of A disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), a protease enzyme involved in degrading extracellular matrix associated with atherosclerosis. Methods and Results: We have studied the cell viability by MTT assay and foam cell formation by oil red O staining. The mRNA and protein expression of ADAMTS-4 was studied using quantitative polymerase chain reaction (qPCR) and Western blotting, respectively. Our study showed that chrysin significantly downregulates the expression of ADAMTS-4 in foam cells. Conclusion: Chrysin's ability to downregulate the expression of ADAMTS-4, a protease involved in degrading the extracellular matrix, bestows upon it a new therapeutic potential for managing atherosclerosis. Highlights: Chrysin downregulates the mRNA and protein expression of ADAMTS-4 in foam cells. [ABSTRACT FROM AUTHOR]

In-stent restenosis(ISR) is a significant cause of long-term prognosis after percutaneous coronary intervention (PCI). The inflammatory response is a critical factor in its development. Unlike the chronic inflammatory process of traditional atherosclerosis, ISR may develop acute coronary events within even months or years, and the inflammatory mechanisms of ISR are more complex. Inflammatory factors regulate various mechanisms, including monocyte macrophage proliferation, endothelial cell damage and repair, foam cell formation, and smooth muscle cell proliferation and migration after PCI. The review briefly describes the classification and risk factors of ISR. It emphasizes the role of various inflammatory factors in ISR to provide new ideas for investigating the inflammatory mechanism of ISR and clinical intervention. [ABSTRACT FROM AUTHOR]

Aim To investigate the impact of bakuchiol (BAK) on lipid accumulation in macrophage-derived foam cell and explore the underlying mechanisms. Methods MTT assay was used to determine the non-toxic concentration of BAK on foam cell. Oil red O staining, NBD cholesterol, and Dil-ox-LDL were used to assess lipid accumulation in foam cell. RT-qPCR and Western blot were utilized to measure mRNA and protein expression, respectively. Results BAK promoted cholesterol effux and reduced lipid accumulation in foam cell. BAK upregulated the mRNA and protein expression levels of ATP-binding cassette transporter A1 (ABCA1) and concurrently downregulated the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2). Treatment with the ERK1/2 activator Ro 67-7476 resulted in decreased ABCA1 protein expression compared with the BAK-treated group. Conclusion BAK reduced lipid accumulation in foam cell by inhibiting ERK1/2 phosphorylation, upregulating ABCA1 expression, and promoting cholesterol efflux, thereby suppressing foam cell formation. [ABSTRACT FROM AUTHOR]

Aim To investigate the effect of theaflavin on oxidized low density lipoprotein (ox-LDL)-induced foam cell formation and oxidative stress in THP-1 macrophages and its mechanism. Methods THP-1 derived macrophages were pretreated with 50 μmol/L theaflavin and (or) 10 μmol/L nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor ML385, then 100 mg/L ox-LDL was added to the cells for 24 h to establish the foam cell model. The effect of theaflavin on THP-1 macrophages viability was evaluated by CCK-8 assay and LDH release. The expression of inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. The release of inflammatory cytokines were detected by enzyme linked immunosorbent assay (ELISA). Intracellular lipid accumulation was detected by Oil red O staining, and lipid absorption was observed by DiL-labeled oxidized low density lipoprotein (DiL-ox-LDL) staining. Reactive oxygen species (ROS) level was detected by DCFH-DA probe. The expression of lipid uptake, cholesterol efflux and oxidative stress-related proteins were detected by Western blot and RT-qPCR. Results Treatment with 100 mg/L ox-LDL significantly decreased cell viability and cholesterol efflux-related protein expressions, increased lipid uptake, accumulation and lipid uptake-related protein expressions, and significantly promoted inflammation and ROS level, as well as the expressions of myeloperoxidase (MPO), NADPH oxidase 2 (NOX2) in THP-1 macrophages (all P<0. 05). After pretreatment with theaflavin, cell viability was increased, intracellular lipid uptake, accumulation and lipid uptake-related protein expressions were significantly reduced, cholesterol efflux-related protein expressions were significantly increased, the expression and release of IL-6, IL-1β and TNF-α were significantly decreased, ROS level was significantly decreased, and the expression of MPO and NOX2 were decreased (all P<0. 05). Pretreatment with theaflavin effectively alleviated intracellular oxidative stress by altering the expression of NRF2, heme oxygenase-1 (HO-1) and Kelch-like ECH-associated protein 1 (KEAP1) in NRF2 signaling pathway, and enhanced the translocation of NRF2 into the nucleus. After pretreatment with ML385, the expression levels of NRF2, HO-1, KEAP1 and CD36 were significantly decreased. Conclusion Theaflavin can significantly inhibit ox-LDL-induced foam cell formation, inflammation, and oxidative stress through NRF2/HO-1 signaling pathway in THP-1 macrophages. [ABSTRACT FROM AUTHOR]

Multiple layered PVDF-CNTs with different CNTs were prepared by facile melt blending process. Due to varied electrical conductivity in each layer, incident electromagnetic (EM) waves could be reflected and absorbed between these layers, and thus their electromagnetic interference (EMI) efficiency was obviously improved. EMI shielding effectiveness of a three- layered PVDF-CNTs with CNTs content of 6, 8, 10 wt. % sequentially, is 36.4 dB, compared to a 27.2 dB of single layered PVDF-8CNTs with a same sample thickness of 2 mm, an increase of 34% was induced. Furthermore, based on different viscoelasticity of PVDF-CNTs with various CNTs content, three- layered PVDF-6–8-10 CNTs foams with a gradient cell structure and thickness of 2 mm, were manufactured by an environment friendly supercritical CO2 batch foaming method, an absolute EM SE value of 35.2 dB at a frequency of 26 GHz was measured. Because of the introduction of microcellular sized cells, the electromagnetic waves were absorbed and reflected inside the cells, cooperated with the multiple reflections between different layers, an increased absorption dominated mechanism in these foamed PVDF-CNTs composites was resulted, which means a successful mechanism transformation from reflection to absorption after foaming. [ABSTRACT FROM AUTHOR]

Glucose-dependent insulinotropic polypeptide (GIP) of the incretin group has been shown to exert pleiotropic actions. There is growing evidence that advanced glycation end products (AGEs), senescent macromolecules formed at an accelerated rate under chronic hyperglycemic conditions, play a role in the pathogenesis of atherosclerotic cardiovascular disease in diabetes. However, whether and how GIP could inhibit the AGE-induced foam cell formation of macrophages, an initial step of atherosclerosis remains to be elucidated. In this study, we address these issues. We found that AGEs increased oxidized low-density-lipoprotein uptake into reactive oxygen species (ROS) generation and Cdk5 and CD36 gene expressions in human U937 macrophages, all of which were significantly blocked by [D-Ala2]GIP(1–42) or an inhibitor of NADPH oxidase activity. An inhibitor of AMP-activated protein kinase (AMPK) attenuated all of the beneficial effects of [D-Ala2]GIP(1–42) on AGE-exposed U937 macrophages, whereas an activator of AMPK mimicked the effects of [D-Ala2]GIP(1–42) on foam cell formation, ROS generation, and Cdk5 and CD36 gene expressions in macrophages. The present study suggests that [D-Ala2]GIP(1–42) could inhibit the AGE-RAGE-induced, NADPH oxidase-derived oxidative stress generation in U937 macrophages via AMPK activation and subsequently suppress macrophage foam cell formation by reducing the Cdk5-CD36 pathway. [ABSTRACT FROM AUTHOR]

Recent findings from the World Heart Federation (WHF) reported a significant increase in cardiovascular disease (CVD)-related deaths, highlighting the urgent need for effective prevention strategies. Atherosclerosis, a key precursor to CVD, involves the accumulation of low-density lipoprotein (LDL) and its oxidation within the endothelium, leading to inflammation and foam cell formation. Ginger extracts, known for their antioxidative and anti-inflammatory properties, show promise in preventing CVD initiation by inhibiting LDL oxidation and reducing foam cell formation. Our results revealed that the active fractions in ginger extracts had antioxidative effects, particularly fractions D and E. Further research is needed to identify the active compounds in these fractions and understand their mechanisms of action. In this context, microfluidic models could offer insights into the effects of ginger on monocyte recruitment in a more physiologically relevant context. Overall, ginger extracts represent a potential novel treatment for preventing CVD initiation, but additional studies are necessary to identify the active molecules in these fractions. [ABSTRACT FROM AUTHOR]

Several lines of evidence have linked the intestinal bacterium Helicobacter cinaedi with the pathogenesis of atherosclerosis, identifying the Cinaedi Antigen Inflammatory Protein (CAIP) as a key virulence factor. Oxidative stress and inflammation are crucial in sustaining the atherosclerotic process and oxidized LDL (oxLDL) uptake. Primary human macrophages and endothelial cells were pre-incubated with 10 µM diphenyl iodonium salt (DPI) and stimulated with 20 µg/mL CAIP. Lectin-like oxLDL receptor (LOX-1) expression was evaluated by FACS analysis, reactive oxygen species (ROS) production was measured using the fluorescent probe H2DCF-DA, and cytokine release was quantified by ELISA assay. Foam cells formation was assessed by Oil Red-O staining, and phosphorylation of p38 and ERK1/2 MAP kinases and NF-κB pathway activation were determined by Western blot. This study demonstrated that CAIP triggered LOX-1 over-expression and increased ROS production in both macrophages and endothelial cells. Blocking ROS abrogated LOX-1 expression and reduced LDL uptake and foam cells formation. Additionally, CAIP-mediated pro-inflammatory cytokine release was significantly affected by ROS inhibition. The signaling pathway induced by CAIP-induced oxidative stress led to p38 MAP kinase phosphorylation and NF-κB activation. These findings elucidate the mechanism of action of CAIP, which heightens oxidative stress and contributes to the atherosclerotic process in H. cinaedi-infected patients. [ABSTRACT FROM AUTHOR]

This study was to investigate the therapeutic effect of Bacillus amyloliquefaciens (Ba) on atherosclerosis (AS). THP-1 monocyte was differentiated to THP-1 macrophage (THP-M) through phorbol 12-myristate 13-acetate. After pre-treatment by 108 cfu/ml Ba lasting 6 h, THP-M was induced with 100 mg/l ox-LDL lasting 48 h to form macrophage foam cell (THP-F). RT-qPCR and flow cytometry were employed to determine the polarization of THP-M and THP-F. ApoE−/− mice with high-fat and high-cholesterol diet were used for constructing an AS model to evaluate the effect of Ba on AS. Our in vitro results showed that Ba vegetative cells pre-treatment distinctly inhibited the levels of iNOS and CD16/CD32 (M1 macrophage markers), and increased the levels of FIZZ1, Ym1, Arg1, CD163, and CD206 (M2 macrophage markers), indicating that Ba pre-treatment promoted anti-inflammatory M2-like polarization both in THP-M and THP-F. Meanwhile, it also suppressed cholesterol uptake, esterification, and hydrolysis, and efflux by THP-M and THP-F. Additionally, our animal experiments demonstrated that Ba vegetative cells treatment suppressed high cholesterol, hyperglycemia, hyperlipidemia, and the release of inflammatory factors (TNF-α, IL-6 and IL-1β) in ApoE−/− AS mice. In a word, our results indicated that Ba may protect against AS through alleviating foam cell formation and macrophage polarization through targeting certain stages of AS. [ABSTRACT FROM AUTHOR]

Despite advances in treatment, atherosclerotic cardiovascular disease remains the leading cause of death in patients with diabetes. Even when risk factors are mitigated, the disease progresses, and thus, newer targets need to be identified that directly inhibit the underlying pathobiology of atherosclerosis in diabetes. A single-cell sequencing approach was used to distinguish the proatherogenic transcriptional profile in aortic cells in diabetes using a streptozotocin-induced diabetic Apoe −/− mouse model. Human carotid endarterectomy specimens from individuals with and without diabetes were also evaluated via immunohistochemical analysis. Further mechanistic studies were performed in human aortic endothelial cells (HAECs) and human THP-1–derived macrophages. We then performed a preclinical study using an activator protein-1 (AP-1) inhibitor in a diabetic Apoe −/− mouse model. Single-cell RNA sequencing analysis identified the AP-1 complex as a novel target in diabetes-associated atherosclerosis. AP-1 levels were elevated in carotid endarterectomy specimens from individuals with diabetes compared with those without diabetes. AP-1 was validated as a mechanosensitive transcription factor via immunofluorescence staining for regional heterogeneity of endothelial cells of the aortic region exposed to turbulent blood flow and by performing microfluidics experiments in HAECs. AP-1 inhibition with T-5224 blunted endothelial cell activation as assessed by a monocyte adhesion assay and expression of genes relevant to endothelial function. Furthermore, AP-1 inhibition attenuated foam cell formation. Critically, treatment with T-5224 attenuated atherosclerosis development in diabetic Apoe −/− mice. This study has identified the AP-1 complex as a novel target, the inhibition of which treats the underlying pathobiology of atherosclerosis in diabetes. Article Highlights: The cell-specific transcriptional profile of vascular cells in diabetes-associated atherosclerosis is not known. Single-cell RNA sequencing analysis not only defined the transcriptional profile of vascular cells in diabetes but also identified the activator protein-1 (AP-1) complex as one of the important transcription factor complexes in flow-mediated endothelial cell activation and foam cell formation. Although previous studies have implicated AP-1 in atherosclerosis, our study has defined the role of AP-1 as a central regulator of a gene expression program linked to endothelial dysfunction and foam cell formation in diabetes. Importantly, inhibition of AP-1 transcription activity with T-5224 attenuated atherosclerosis development in vivo in diabetes. [ABSTRACT FROM AUTHOR]

Cathepsin B (CTSB) is a member of the cysteine protease family, primarily responsible for degrading unnecessary organelles and proteins within the acidic milieu of lysosomes to facilitate recycling. Recent research has revealed that CTSB plays a multifaceted role beyond its function as a proteolytic enzyme in lysosomes. Importantly, recent data suggest that CTSB has significant impacts on different cardiac pathological conditions, such as atherosclerosis (AS), myocardial infarction, hypertension, heart failure and cardiomyopathy. Especially in the context of AS, preclinical models and clinical sample imaging data indicate that the cathepsin activity‐based probe can reliably image CTSB activity in foam cells and atherosclerotic plaques; concurrently, it allows synchronous diagnostic and therapeutic interventions. However, our knowledge of CTSB in cardiovascular disease is still in the early stage. This paper aims to provide a comprehensive review of the significance of CTSB in cardiovascular physiology and pathology, with the objective of laying a theoretical groundwork for the development of drugs targeting CTSB. [ABSTRACT FROM AUTHOR]

Background: Macrophage-derived foam cells are essential in the progression of atherosclerosis (AS). Based on our previous study, the Huxin Formula (HXF), a traditional Chinese medicine formula, demonstrates potential in anti-atherosclerosis. Nevertheless, it is still unknown how HXF affects the formation of foam cells derived from THP-1 macrophages. Purpose: This research aims to examine the preventive role of HXF in the development of foam cells and its underlying molecular mechanism. Methods: THP-1 derived macrophages and THP-1 cells overexpressing LOX-1 (LV-OLR1) were exposed to ox-LDL to establish foam cell models, and then treated with HXF. Meantime, Oil red O staining was used to detect lipid droplet production. ELISA kit was performed to measure intracellular levels of IL-6 and TGF-β. RT-qPCR and Western Blot were then utilized to determine the LOX-1 and NF-κB mRNA/protein levels. Results: The findings indicated that HXF treatment potently reduced the lipid accumulation, downregulated IL-6 levels and upregulated TGF-β levels. However, this impact was almost reversed when LOX-1 was overexpressed in THP-1 cells stimulated with ox-LDL. Moreover, THP-1 were treated with HXF markedly reduced the levels of LOX-1 and NF-κB mRNA/protein, whereas overexpressing LOX-1 significantly reversed this effect. Conclusion: HXF reduced the formation of foam cell in ox-LDL-stimulated THP-1 macrophages via inhibiting lipid accumulation and inflammation through regulating the LOX-1/ NF-κB pathway. These present findings further indicate a potential beneficial role of HXF in ameliorating atherosclerosis and foam cell formation, while provide a novel potential therapeutic strategy for preventing atherosclerosis. [ABSTRACT FROM AUTHOR]

In this study, the effects of two environmentally-friendly pulping methods along with two different reactive compatibilization methods on the foamability of poly (lactic acid) (PLA)/rice straw (RS) biocomposites have been investigated. RS as an annually renewable agricultural waste is low-cost and available. Melt-compounding and melt-foaming processes were performed through a twin-screw extrusion processing. The correlations between processing and microstructure were studied. The findings show that the RS pulping with sodium bicarbonate (SB) solution leads to the lignocellulosic particles with a porous structure. The structure causes the filler/matrix mechanical engagement and improves the interfacial adhesion and rheological properties, hence forming smaller cells with the narrowest cell size distribution. In contrast, applying ultrasound waves on the RS pulp brings the particles to very smooth surfaces. These surfaces have the highest activity at the cell nucleation stage and considerably increase the foam's cell density. The reactive compatibilizers based on epoxy and maleic anhydride groups show opposing effects on the biocomposite microstructure, depending on the RS pulp type. The use of the reactive compatibilizers in the PLA/RS pulp treated with SB led to lighter foams with larger cells and higher cell densities and void fractions. Whereas the incorporation of the compatibilizers into the biocomposites containing RS pulp treated with SB and ultrasonic waves resulted in noticeably lower cell density and larger foam density. The extruded biocomposite foams with closed-cell microstructure can be used in insulation and packaging applications. [ABSTRACT FROM AUTHOR]

Aims: Cardiovascular disease remains a major global health concern, with atherosclerosis (AS) being a significant contributor. Vulnerable plaques play a critical role in acute cardiovascular events. Syndecan-1 (SDC-1), a vital membrane proteoglycan in the vascular endothelial glycocalyx, is believed to be associated with plaque progression. However, its precise relationship with severity and vulnerability of atherosclerotic plaque remains unclear. This study aimed to investigate SDC-1 expression and its potential correlation with plaque vulnerability in ApoE-/- atherosclerosis mouse model. Methods and results: Eight-week-old mice were induced into the AS model using a high-fat diet (HFD) and/or partial ligation of the left common carotid artery (PLCA), with a chow diet (CD) control group. After 16 weeks, plaques in the aortic root showed the following order: HFD + PLCA group > HFD group > CD + PLCA group > CD group. Immunohistochemistry revealed heightened accumulation of lipid/foam cells and CD68-labeled macrophages in the plaques, elevated vascular endothelial growth factor (VEGF), and matrix Metalloproteinase-9 (MMP-9) in the HFD + PLCA group's plaques, along with reduced collagen and α-SMA-labeled smooth muscle cells, resulting in the highest vulnerability index value. Immunohistofluorescence analysis of frozen plaque sections showed significantly higher SDC-1 expression in the AS mice group compared to the CD group, both positively correlated with plaque vulnerability. Serum analysis demonstrated elevated levels of SDC1, sphingosine 1-phosphate (S1P), and VEGF-A in the AS mice, all positively correlated with plaque vulnerability. Multivariate analysis identified SDC1 as an independent predictor of plaque vulnerability. Conclusion: This study enhances our understanding of plaque vulnerability mechanisms and presents SDC1 as a potential biomarker for atherosclerosis. These findings underscore the importance of addressing modifiable risk factors, such as diet and hemodynamics and suggest the utility of serum SDC1 as a valuable clinical marker. Ultimately, these insights may lead to more effective strategies in combating cardiovascular diseases and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is the primary pathology behind various cardiovascular diseases and the leading cause of death and disability globally. Recent evidence suggests that AS is a chronic vascular inflammatory disease caused by multiple factors. In this context, the NLRP3 inflammasome, acting as a signal transducer of the immune system, plays a critical role in the onset and progression of AS. The NLRP3 inflammasome is involved in endothelial injury, foam cell formation, and pyroptosis in AS. Therefore, targeting the NLRP3 inflammasome offers a new treatment strategy for AS. This review highlights the latest insights into AS pathogenesis and the pharmacological therapies targeting the NLRP3 inflammasome, focusing on optimal targets for small molecule inhibitors. These insights are valuable for rational drug design and the pharmacological assessment of new targeted NLRP3 inflammasome inhibitors in treating AS. [ABSTRACT FROM AUTHOR]

The formation of macrophage-derived foam cells has been recognized as the pathological hallmark of atherosclerotic diseases. However, the pathological evolution dynamics and underlying regulatory mechanisms remain largely unknown. Herein, we introduce a single-particle rotational microrheology method for pathological staging of macrophage foaming and antiatherosclerotic explorations by probing the dynamic changes of lysosomal viscous feature over the pathological evolution progression. The principle of this method involves continuous monitoring of out-of-plane rotation-caused scattering brightness fluctuations of the gold nanorod (AuNR) probe-based microrheometer and subsequent determination of rotational relaxation time to analyze the viscous feature in macrophage lysosomes. With this method, we demonstrated the lysosomal viscous feature as a robust pathological reporter and uncovered three distinct pathological stages underlying the evolution dynamics, which are highly correlated with a pathological stage-dependent activation of the NLRP3 inflammasome-involved positive feedback loop. We also validated the potential of this positive feedback loop as a promising therapeutic target and revealed the time window-dependent efficacy of NLRP3 inflammasome-targeted drugs against atherosclerotic diseases. To our knowledge, the pathological staging of macrophage foaming and the pathological stage-dependent activation of the NLRP3 inflammasome-involved positive feedback mechanism have not yet been reported. These findings provide insights into in-depth understanding of evolutionary features and regulatory mechanisms of macrophage foaming, which can benefit the analysis of effective therapeutical drugs as well as the time window of drug treatment against atherosclerotic diseases in preclinical studies. [ABSTRACT FROM AUTHOR]

The rising incidences of atherosclerosis have necessitated efforts to identify novel targets for therapeutic interventions. In the present study, we observed increased expression of the mechanosensitive calcium channel Piezo1 transcript in mouse and human atherosclerotic plaques, correlating with infiltration of PIEZO1-expressing macrophages. In vitro administration of Yoda1, a specific agonist for PIEZO1, led to increased foam cell apoptosis and enhanced phagocytosis by macrophages. Mechanistically, PIEZO1 activation resulted in intracellular F-actin rearrangement, elevated mitochondrial ROS levels and induction of mitochondrial fragmentation upon PIEZO1 activation, as well as increased expression of anti-inflammatory genes. In vivo, ApoE−/− mice treated with Yoda1 exhibited regression of atherosclerosis, enhanced stability of advanced lesions, reduced plaque size and necrotic core, increased collagen content, and reduced expression levels of inflammatory markers. Our findings propose PIEZO1 as a novel and potential therapeutic target in atherosclerosis. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a major reason for the high morbidity and mortality of cardiovascular diseases. Macrophage inflammation and foam cell formation are the key pathological processes of atherosclerosis. Ginsenoside compound K (CK) is a metabolite derived from ginseng. CK has anti atherosclerotic effect, but the molecular mechanism remains to be elucidated. We aim to explore the protective effect of CK against ox-LDL-induced inflammatory responses and foam cells formation in vitro and explore its potential mechanisms. Through the results of oil red O staining, Western blot, and qPCR, we found that CK significantly inhibited the foam cell formation, reduced the expression of SR-A1 and increased ABCA1 and ABCG1 expression. In addition, CK increased the number of autophagosomes and upregulated the LC3II/LC3I ratio and the expressions of ATG5 and Beclin-1 but decreased p62 expression. Moreover, CK significantly inhibited the NF-kB, p38, and JNK MAPK signaling pathway. Altogether, CK attenuated macrophage inflammation and foam cell formation via autophagy induction and by modulating NF-kB, p38, and JNK MAPK signaling. Thus, CK has potential as a therapeutic drug for atherosclerosis. [ABSTRACT FROM AUTHOR]

Introduction: An ongoing inflammatory is condition in atherosclerosis in which there is fat streak, a buildup of foam cells with lipid content in the artery's intimal layer act as precursor to atherosclerosis. Peltophorum pterocarpum stem bark extract found to be effective in inhibition of platelet aggregation and possess anti-inflammatory effect that may be useful in treating atherosclerosis. Therefore, the goal of the current investigation is to ascertain if the ethanolic extract of Peltophorum pterocarpum stem bark (EEPP) has anti-atherosclerosis effect in Wistar rats using a high fat diet in atherosclerotic induced atherosclerosis model for 60 days. Atherosclerosis was induced in male Wistar rats by giving them a high-fat diet. Following induction, oral doses of EEPP (250, 500 mg/kg) and atorvastatin (10 mg/kg) were administered orally to the rats for the following 20 days. Methods: The literature was searched using PubMed and google scholar search Engines. A total 30 plants were mentioned through database searches. Papers from between 1999 and 2022 were included. An attempt was made to document relevant literature that is only focused on potential effect of various plants in treatment of atherosclerosis. Results: In comparison to the control group, EEPP was able to significantly lower the raised serum levels of total cholesterol, triglyceride, LDL, and VLDL while significantly increasing the levels of HDL. When compared to the diseased control group, EEPP significantly lessened damage to the endothelial lining of the aorta and had an impact on lumen size by lowering cholesterol buildup. [ABSTRACT FROM AUTHOR]

Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs of foam cells. Using knockout and transgenic mice of both sexes, here we show that LDAH inhibits atherosclerosis development and promotes stable lesion architectures. Broad and targeted lipidomic analyzes of primary macrophages and comparative lipid profiling of atheroma identified a broad impact of LDAH on esterified sterols, including natural liver X receptor (LXR) sterol ligands. Transcriptomic analyzes coupled with rescue experiments show that LDAH modulates the expression of prototypical LXR targets and leads macrophages to a less inflammatory phenotype with a profibrotic gene signature. These studies underscore the role of LDs as reservoirs and metabolic hubs of bioactive lipids, and suggest that LDAH favorably modulates macrophage activation and protects against atherosclerosis via lipolytic mobilization of regulatory sterols. The mechanisms and consequences of bioactive lipids release from lipid droplets remain poorly understood. Here the authors link a lipid droplet enzyme to mobilization of esters of regulatory sterols in foam cells and protection against atherosclerosis. [ABSTRACT FROM AUTHOR]

The objective of this study was to elucidate the protective role of quercetin in atherosclerosis by examining its effect on the phenotypic switch of vascular smooth muscle cells (VSMCs) to macrophage-like cells and the underlying regulatory pathways. Aorta tissues from apolipoprotein E-deficient (ApoE KO) mice fed a high-fat diet (HFD), treated with or without 100 mg/kg/day quercetin, were analyzed for histopathological changes and molecular mechanisms. Quercetin was found to decrease the size of atherosclerotic lesions and mitigate lipid accumulation induced by HFD. Fluorescence co-localization analysis revealed a higher presence of macrophage-like vascular smooth muscle cells (VSMCs) co-localizing with phospho-Janus kinase 2 (p-JAK2), phospho-signal transducer and activator of transcription 3 (p-STAT3), and Krüppel-like factor 4 (KLF4) in regions of foam cell aggregation within aortic plaques. However, this co-localization was reduced following treatment with quercetin. Quercetin treatment effectively inhibited the KLF4-mediated phenotypic switch in oxidized low-density lipoprotein (ox-LDL)-loaded mouse aortic vascular smooth muscle cells (MOVAS), as indicated by decreased expressions of KLF4, LGALS3, CD68, and F4/80, increased expression of alpha smooth muscle actin (α-SMA), reduced intracellular fluorescence Dil-ox-LDL uptake, and decreased lipid accumulation. In contrast, APTO-253, a KLF4 activator, was found to reverse the effects of quercetin. Furthermore, AG490, a JAK2 inhibitor, effectively counteracted the ox-LDL-induced JAK2/STAT3 pathway-dependent switch to a macrophage-like phenotype and lipid accumulation in MOVAS cells. These effects were significantly mitigated by quercetin but exacerbated by coumermycin A1, a JAK2 activator. Our research illustrates that quercetin inhibits the KLF4-mediated phenotypic switch of VSMCs to macrophage-like cells and reduces atherosclerosis by suppressing the JAK2/STAT3 pathway. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]