Association between glycated albumin and adverse outcomes in patients with heart failure.

AIMS/INTRODUCTION: Diabetes mellitus is a traditional risk factor for heart failure (HF), and glycated albumin (GA) is a marker to assess short-term glycemic control. Whether GA has prognostic significance in patients with HF remains unclear. MATERIALS AND METHODS: A total of 717 patients with HF were enrolled in the prospective cohort study. Patients were grouped by the normal upper limit of GA (17%). Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate the association between GA and prognosis. RESULTS: During a mean follow-up of 387 days, 232 composite endpoint events of hospitalization for HF or all-cause death occurred. Kaplan-Meier analysis showed a higher rate of adverse events in the higher GA group (GA >17%; log-rank test P < 0.001). GA was an independent predictor of adverse events, both as a continuous variable (per 1% change: hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.00-1.06, P = 0.030) and as a categorical variable (GA >17%: HR 1.36, 95% CI 1.03-1.80, P = 0.032). Restricted cubic splines showed a linear association between GA and adverse events (P for non-linearity = 0.231). There was no significant difference in adverse outcome risk between those with diabetes and GA ≤17% and those without diabetes, whereas the prognosis was worse in those with diabetes and GA >17% (HR 1.56, 95% CI 1.16-2.11, P = 0.004). Compared to the group with normal levels of GA and glycated hemoglobin, the group with GA >17% and glycated hemoglobin >6.5% had a higher risk of adverse events (HR 1.49, 95% CI 1.06-2.10, P = 0.022). CONCLUSIONS: GA was an independent predictor of HF prognosis. Combining GA and glycated hemoglobin might improve the predictive power of adverse outcomes in patients with HF.

BMI moderates the relationship between depression and chronic obstructive pulmonary disease: A cross­sectional survey.

BACKGROUND: Prior research has established a connection between depression and chronic obstructive pulmonary disease (COPD). However, the influence of age and BMI on this association remains unclear. OBJECTIVES: We used the National Health and Nutrition Examination Survey (NHANES) database to explore the relationship between depression and COPD, and to investigate whether age and Body mass index (BMI) act as moderators in this relationship. METHODS: We analyzed data from 10,940 participants in the NHANES database. Depression served as the independent variable. COPD status served as the outcome variable. We employed multivariable logistic regression to examine the relationship between depression and COPD. RESULTS: Of the 10,940 respondents surveyed, about 3.9 % had COPD and 8.5 % had depression. The prevalence of depression in COPD patients was significantly greater than the prevalence of overall respondents (21.1 % VS.8.5 %). We found that the association between depression and COPD was mediated by BMI status. Controlling for other covariates, the association between depression and COPD increased significantly. For the underweight group, the impact of depression on the risk of COPD was lower compared to the normal BMI group. CONCLUSION: This study confirms a significant association between depression and COPD, with BMI serving as a moderator. These findings enhance our understanding of the complex interplay between depression and COPD and underscore the importance of considering individual physical health characteristics in clinical assessments. The results have significant implications for clinical practice and public health policymaking.

IRF5 governs macrophage adventitial infiltration to fuel abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the expansion of the aortic wall. One of the most significant features is the infiltration of macrophages in the adventitia, which drives vasculature remodeling. The role of macrophage-derived interferon regulatory factor 5 (IRF5) in macrophage infiltration and AAA formation remains unknown. RNA sequencing of AAA adventitia identified Irf5 as the top significantly increased transcription factor that is predominantly expressed in macrophages. Global and myeloid cell-specific deficiency of Irf5 reduced AAA progression, with a marked reduction in macrophage infiltration. Further cellular investigations indicated that IRF5 promotes macrophage migration by direct regulation of downstream phosphoinositide 3-kinase γ (PI3Kγ, Pik3cg). Pik3cg ablation hindered AAA progression, and myeloid cell-specific salvage of Pik3cg restored AAA progression and macrophage infiltration derived from Irf5 deficiency. Finally, we found that IRF5 and PI3Kγ expression in the adventitia is significantly increased in patients with AAA. These findings reveal that the IRF5-dependent regulation of PI3Kγ is essential for AAA formation.

Removal of a pulmonary artery foreign body during pulse ablation in a patient with atrial fibrillation: A case report.

BACKGROUND: Foreign bodies in the pulmonary circulation have been documented in the literature and are typically caused by interventional procedures. However, reports of pulmonary artery foreign bodies during femoral vein puncture are rare, and there is no description of this complication from the guidewire surface flows into the pulmonary artery during a pulse ablation in a patient with atrial fibrillation. CASE SUMMARY: We described a case in which a linear foreign body suddenly appeared on fluoroscopy image during pulsed ablation of atrial fibrillation. Multiposition angiography showed that the foreign body was currently lodged in the pulmonary artery but was hemodynamically stable. We then chose to use an interventional approach to remove the foreign body from the pulmonary artery. This foreign body was subsequently confirmed to be from the hydrophilic coating of the guidewire surface. This may be related to the difficulties encountered during the puncture of the femoral vein. This is a rare and serious complication of femoral vein puncture. Therefore, we reported this case in order to avoid a similar situation. CONCLUSION: Mismatches between interventional devices from different manufacturers used for femoral venipuncture may result in pulmonary artery foreign bodies.

Rehmannia alcohol extract inhibits neuropeptide secretion and alleviates osteoarthritis pain through cartilage protection.

Osteoarthritis (OA) is a common joint disease characterized by chronic pain, and the perception of pain is closely associated with brain function and neuropeptide regulation. Rehmannia is common plant herb with anti-inflammatory and analgesic properties that is used to treat OA. However, it is unclear whether Rehmannia alleviates OA-related pain via regulation of neuropeptides and brain function. We examined the pain relief regulatory pathway in OA after treatment with Rehmannia by verifying the therapeutic effect of Rehmannia alcohol extract in vivo and vitro and exploring of the potential mechanism underlying the analgesic effect of Rahmanian using functional magnetic resonance imaging and measuring neuropeptide secretion. Our results showed that Rehmannia alcohol extract and the related active ingredient, Rehmannioside D, can delay cartilage degradation and alleviate inflammation in OA rats. The Rehmannia alcohol extract can also relieve OA pain, reduce the secretion of calcitonin gene-related peptide (CGRP) and substance P (SP), and reverse the pathological changes in the cerebral cortex and hippocampus. Our research results demonstrate that Rehmannia alleviates OA pain by protecting cartilage, preventing the stimulation of inflammatory factors on neuropeptide secretion, and influencing the relevant functional areas of the brain.

Pneumonia due to Mycobacterium cosmeticum in a patient with systemic sclerosis: A case report.

Pulmonary infection due to Mycobacterium cosmeticum was reported in only two patients previously. More studies are warranted to define its characteristics and treatments. We report a systemic sclerosis patient who had a pulmonary infection due to M. cosmeticum and then successfully recovered after treatment with combination antibiotic regimen.

NADPH Selective Depletion Nanomedicine-Mediated Radio-Immunometabolism Regulation for Strengthening Anti-PDL1 Therapy against TNBC.

Anti-PD(L)1 immunotherapy recently arises as an effective treatment against triple-negative breast cancer (TNBC) but is only applicable to a small portion of TNBC patients due to the low PD-L1 expression and the immunosuppressive tumor microenvironment (TME). To address these challenges, a multifunctional "drug-like" copolymer that possesses the auto-changeable upper critical solution temperature and the capacity of scavenging reduced nicotinamide adenine dinucleotide phosphate (NADPH) inside tumor cells is synthesized and employed to develop a hypoxia-targeted and BMS202 (small molecule antagonist of PD-1/PD-L1 interactions)-loaded nanomedicine (BMS202@HZP NPs), combining the anti-PD-L1 therapy and the low-dose radiotherapy (LDRT) against TNBC. In addition to the controlled release of BMS202 in the hypoxic TNBC, BMS202@HZP NPs benefit the LDRT by upregulating the pentose phosphate pathway (PPP, the primary cellular source for NADPH) of TME whereas scavenging the NADPH inside tumor cells. As a result, the BMS202@HZP NPs-mediated LDRT upregulate the PD-L1 expression of tumor to promote anti-PD-L1 therapy response while reprogramming the immunometabolism of TME to alleviate its immunosuppression. This innovative nanomedicine-mediated radio-immunometabolism regulation provides a promising strategy to reinforce the anti-PD-L1 therapy against TNBC.

Response of microbial community assembly and succession pattern to abiotic factors during the second round of light-flavor Baijiu fermentation.

The regulation of microbial communities is an important strategy for fermentation management. Dynamic microbiota during the Baijiu fermentation is shaped by a variety of abiotic factors. Therefore, this study aims to investigate the effects of the microbiota of the fermentation starter Daqu on the microbial assembly and the interaction of microbiota succession and abiotic factors during the second round (Ercha) of light-flavor Baijiu fermentation. The results revealed that Streptomyces, Bacillus, Lactobacillus, and Staphylococcus were the dominant bacterial genera in the initial fermentation, while Lactobacillus was dominant during the middle and later stages. Pichia and Saccharomycopsis were the dominant fungal genera during the whole fermentation process. A total of 54 volatile compounds were identified during the fermentation, among which 15 compounds, mainly including ethyl acetate, diethyl azelate, ethyl 2-hydroxyisocaproate, 3-furaldehyde, and ethylidene diacetate, were identified as important flavor metabolites. The SourceTracker software revealed that Daqu contributed 52.3 % of the bacterial community and 38.6 % of the fungal community to the fermentation. Ethanol, moisture, and pH were the major factors regulating the succession of dominant bacteria and fungi during the fermentation. The microbial succession and co-occurrence pattern driven by abiotic factors played a crucial role in shaping flavor profiles. These results provide guidance for controlling the fermentation process by optimizing operational parameters or bioaugmentation with specific microbes.

Research Progress of Conjugated Nanomedicine for Cancer Treatment.

The conventional cancer therapeutic modalities include surgery, chemotherapy and radiotherapy. Although immunotherapy and targeted therapy are also widely used in cancer treatment, chemotherapy remains the cornerstone of tumor treatment. With the rapid development of nanotechnology, nanomedicine is believed to be an emerging field to further improve the efficacy of chemotherapy. Until now, there are more than 17 kinds of nanomedicine for cancer therapy approved globally. Thereinto, conjugated nanomedicine, as an important type of nanomedicine, can not only possess the targeted delivery of chemotherapeutics with great precision but also achieve controlled drug release to avoid adverse effects. Meanwhile, conjugated nanomedicine provides the platform for combining several different therapeutic approaches (chemotherapy, photothermal therapy, photodynamic therapy, thermodynamic therapy, immunotherapy, etc.) with the purpose of achieving synergistic effects during cancer treatment. Therefore, this review focuses on conjugated nanomedicine and its various applications in synergistic chemotherapy. Additionally, the further perspectives and challenges of the conjugated nanomedicine are also addressed, which clarifies the design direction of a new generation of conjugated nanomedicine and facilitates the translation of them from the bench to the bedside.

Intelligent Nanomedicine Approaches Using Medical Gas-Mediated Multi-Therapeutic Modalities Against Cancer.

The emerging area of gas-mediated cancer treatment has received widespread attention in the medical community. Featuring unique physical, chemical, and biological properties, nanomaterials can facilitate the delivery and controllable release of medicinal gases at tumor sites, and also serve as ideal platforms for the integration of other therapeutic modalities with gas therapy to augment cancer therapeutic efficacy. This review presents an overview of anti-cancer mechanisms of several therapeutic gases: nitric oxide (NO), hydrogen sulfide (H2S), carbon monoxide (CO), oxygen (O2), and hydrogen (H2). Controlled release behaviors of gases under different endogenous and exogenous stimuli are also briefly discussed, followed by their synergistic effects with different therapeutic modes. Moreover, the potential challenges and future prospects regarding gas therapy based on nanomaterials are also described, aiming to facilitate the advancement of gas therapeutic nanomedicine in new frontiers for highly efficient cancer treatment.

Verification of pain-related neuromodulation mechanisms of icariin in knee osteoarthritis.

Knee osteoarthritis (KOA) is a common disease with no specific treatment. Icariin (ICA) is considered an agent for KOA. This study aimed to confirm the pain-related neuromodulation mechanisms of ICA on KOA. Three experiments were designed: (1) verifying the therapeutic effects of ICA in vivo and in vitro, (2) exploring the potential pain-related neuromodulation pathways involved in ICA treatment by functional magnetic resonance imaging (fMRI) and virus retrograde tracing (VRT) and (3) confirming the pain-related targets by tandem mass tag (TMT)-based quantitative proteomics and bioinformatic analyses. Experiment 1 verified the efficacy of ICA in OA animal and cell models. Experiment 2 found a series of brain regions associated with KOA reversed by ICA treatment, indicating that a pain-related hypothalamic-mediated neuromodulation pathway and an endocannabinoid (EC)-related pathway contribute to ICA mechanisms. Experiment 3 explored and confirmed four pain-related genes involved in KOA and ICA treatment. We confirmed the key role of pain-related neuromodulation mechanisms in ICA treatment associated with its analgesic effect. Our findings contribute to considering ICA as a novel therapy for KOA.

Heme Oxygenase-1 in Macrophages Impairs the Perfusion Recovery After Hindlimb Ischemia by Suppressing Autolysosome-Dependent Degradation of NLRP3.

[Figure: see text].

Cutting environmental footprints of maize systems in China through Nutrient Expert management.

Excessive fertilizer consumption, poor management, and intense pollution currently restrict sustainable agriculture in China. To address these problems, two 9-year experiments involving typical maize production systems in Northcentral China (summer maize) and Northeast China (spring maize) were conducted to evaluate the effectiveness of Nutrient Expert (NE) management, a Nutrient Decision Support System which combines 4 R nutrient management with improved varieties and optimized plant density, on reducing carbon (C) and nitrogen (N) footprints. The mean grain yields under NE were 7.4 and 11.5 tons ha-1, which were 3.9% and 6.9% higher than those of local farmers' practices (FP) in the summer and spring maize systems, respectively; the N-derived (affected by N fertilization) yield accounted for 21.7% and 73.5% of the total yield under NE, respectively. Compared with FP, NE achieved 21.8% and 16.0% lower reactive nitrogen (Nr) losses, 18.4% and 20.9% lower greenhouse gas (GHG) emissions, 24.8% and 21.4% smaller N footprints (9.1 and 2.3 kg N ton-1 grain), and 21.5% and 26.0% smaller C footprints (436 and 206 kg CO2 eq ton-1 grain) in summer and spring maize, respectively. NE reduced the N-derived N and C footprints by 30.3% and 27.2% in summer maize and 22.9% and 28.0% in spring maize, respectively, as a result of greater yields and optimal N management. Moreover, compared with summer maize, spring maize showed significantly smaller N-derived N (12.6-fold) and C (7.2-fold) footprints. The results demonstrated the ability of long-term NE management to sustain maize yields, reduce Nr losses and GHG emissions, and cut C and N footprints, indicating its potential suitability as an alternative management for sustainable agriculture. Moreover, the summer maize system still had considerable potential for environmental footprints reduction even when current NE management practices were adopted.

Estimation of nitrogen supply for winter wheat production through a long-term field trial in China.

Excessive synthetic nitrogen (N) applications, high mineral N accumulation and low N use efficiency (NUE) are current issues in intensively cultivated winter wheat production system impeding the sustainable development of agriculture in China. To solve these problems, soil accumulated N in the top 1 m of the soil profile before sowing (Nsoil), returned straw-N from the previous maize crop (Nstraw) and fertilizer N application (Nfertilizer) should be comprehensively considered N supply sources in N management. As such, the objective of this research was to determine the optimal total N supply (TNsupply) level needed to meet crop requirements while minimizing environmental impacts. A 9-year on-farm experiment was conducted in accordance with a split-plot design involving two different fertilizer management systems (main treatments) and three N application strategies (sub treatments). Extensive TNsupply levels (ranging from 61 kg ha-1 to 813 kg ha-1) were detected, and relative yield (RY), N input and N output in response to the TNsupply were measured. The relationships between TNsupply and RY, N input, and N output strongly fit linear-plateau, linear, and linear-plateau models, respectively. The minimum TNsupply levels needed to achieve the maximum RY and N output were 325 and 392 kg ha-1, respectively. On the basis of N supply capacity, the TNsupply was removed from the growing system by 61% (N input). As the N input increased past 209 kg ha-1, the NUE declined, at which point the TNsupply reached 433 kg ha-1. Therefore, the suitable TNsupply should range from 325 kg ha-1 (ensuring a total N supply for high yield and N uptake) to 433 kg ha-1 (obtaining a relatively higher NUE and less N loss to the environment). The TNsupply was highlighted to be an indicator for use in N management recommendations. Considering the average high N accumulation in winter wheat production systems, N management should essentially take into account the consumption of Nsoil, the levels of Nstraw and the minimum application of Nfertilizer to obtain high yields while minimizing environmental impacts under suitable TNsupply levels.

Formaldehyde and VOC emissions from plywood panels bonded with bio-oil phenolic resins.

Pyrolysis bio-oil was used to partially substitute for phenol in reacting with formaldehyde for the production of bio-oil phenol formaldehyde plywood (BPFP) panels, with the phenol substitution ratio being 20%, 40%, or 60%. Emissions of formaldehyde and volatile organic compounds (VOCs) from the BPFP panels were studied using solid-phase micro-extraction (SPME) followed by headspace gas chromatography/mass spectrometry (GC/MS), and were compared to those from the phenol formaldehyde plywood (PFP) panels. The sources for VOCs were analyzed, and the health risks associated with the BPFP were examined. Results showed that at 80 °C: (1) Formaldehyde emissions from the BPFP panels were increased to about 4 times that of PFP; (2) VOCs emissions were significantly reduced by up to 84.9% mainly due to the greatly reduced phenol emissions, although the total number of VOCs was increased from 20 to 35; (3) BPFP presents greatly increased carcinogenic and non-carcinogenic health risks because of its much stronger emissions of formaldehyde, N,N-dimethylformamide, benzofuran, furfural, and many chemicals from the bio-oil. It is highly advisable that the health risks are properly taken care of before the wide application of BPFP, or similar bio-oil based engineered wood products.

Data on Tougu Xiaotong capsules may inhibit p38 MAPK pathway-mediated inflammation in vitro.

The Tougu Xiaotong capsule (TXC) is a traditional herbal compound used to treat osteoarthritis (OA) in China. We performed fingerprint analysis with HPLC for the quality control of TXC. Its composition was identified by the comparison of the spectrogram and chromatographic peak of retention time with a reference substance. TXC was found to contain paeoniflorin, isofraxidin, ferulic acid, and rosmarinic acid. The chondrocytes were identified by immunohistochemical staining using collagen II. Chondrocytes that were positive for collagen II were stained brown in the cytoplasm. The toll-like receptor 4 (TLR4) was expressed on the chondrocyte membrane, which was observed using immunofluorescence microscopy. The nuclei were stained blue by 4',6-diamidino-2-phenylindole (DAPI) and TLR4 was stained green. These were observed using laser scanning confocal microscopy. The successful establishment of LPS-exposed chondrocytes was confirmed using enzyme-linked immunosorbent assay (ELISA). Lipopolysaccharide (LPS) administration significantly reduced the levels of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), and a maximum effect was observed at 8 h. We believe that these methods will be useful in future investigations of OA. This data article is related to the research article "Tougu Xiaotong capsules may inhibit p38 MAPK pathway-mediated inflammation: In vivo and in vitro verification" [1].

Rabies Virus Pseudotyped with CVS-N2C Glycoprotein as a Powerful Tool for Retrograde Neuronal Network Tracing.

Efficient viral vectors for mapping and manipulating long-projection neuronal circuits are crucial in structural and functional studies of the brain. The SAD strain rabies virus with the glycoprotein gene deleted pseudotyped with the N2C glycoprotein (SAD-RV(ΔG)-N2C(G)) shows strong neuro-tropism in cell culture, but its in vivo efficiency for retrograde gene transduction and neuro-tropism have not been systematically characterized. We compared these features in different mouse brain regions for SAD-RV-N2C(G) and two other widely-used retrograde tracers, SAD-RV(ΔG)-B19(G) and rAAV2-retro. We found that SAD-RV(ΔG)-N2C(G) enhanced the infection efficiency of long-projecting neurons by ~10 times but with very similar neuro-tropism, compared with SAD-RV(ΔG)-B19(G). On the other hand, SAD-RV(ΔG)-N2C(G) had an infection efficiency comparable with rAAV2-retro, but a more restricted diffusion range, and broader tropism to different types and regions of long-projecting neuronal populations. These results demonstrate that SAD-RV(ΔG)-N2C(G) can serve as an effective retrograde vector for studying neuronal circuits.

Tougu Xiaotong capsules may inhibit p38 MAPK pathway-mediated inflammation: In vivo and in vitro verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Tougu Xiaotong capsules (TXC) are an herbal compound commonly used to treat osteoarthritis (OA) in China. AIM OF THE STUDY: We attempted to verify TXC's therapeutic effects and mechanisms related to the p38 mitogen-activated protein kinase (MAPK) pathway in vivo and in vitro. MATERIALS AND METHODS: TXC's therapeutic effects were assessed by observing cartilage degeneration and inflammatory factors in a modified Hulth's model (in vivo) and a lipopolysaccharides (LPS)-exposed cellular model (in vitro). The expression of biomarkers related to p38 MAPK pathway-mediated inflammation was also investigated. RESULTS: TXC treatment reversed cartilage degeneration related biomarkers (ADAMTS 4, ADAMTS 5, Col I, Col V, MMP 3, MMP 9, and MMP 13) and inflammation factors (IL-1ß, TNF-α, and IL-6) in both the animal and cellular OA models. Expression of p-p38 MAPK was downregulated following TXC administration, and changes to microRNAs in the cellular models were recovered. These results indicated that the p38 MAPK pathway-related mechanism may involve therapeutic effects of TXC. CONCLUSIONS: This study verified TXC's efficacy to treat OA in vivo and in vitro and suggests that p38 MAPK pathway-related mechanisms may be involved in TXC's therapeutic effects.

The responses of extracellular enzyme activities and microbial community composition under nitrogen addition in an upland soil.

Tremendous amounts of nitrogen (N) fertilizer have been added to arable lands, often resulting in substantial effects on terrestrial ecosystems, including soil acidification, altered enzyme activities and changes in microbial community composition. Soil microbes are the major drivers of soil carbon (C) and N cycling; therefore, understanding the response of microbial communities to elevated N inputs is of significant importance. This study was carried out to investigate the influences of different N fertilization rates (0, 182, and 225 kg ha-1 representing control, low, and high N supply for each crop season for summer maize and winter wheat) on soil biochemical attributes, extracellular enzyme activities, and the microbial community composition in a winter wheat-summer maize rotation cropping system in north-central China. The results showed that N addition significantly decreased the soil pH in both the wheat and maize seasons. Microbial biomass N (MBN) decreased following N fertilization in the wheat season, while the opposite trend in MBN was observed in the maize season. Response ratio analysis showed that the activities of enzymes involved in C, N, and phosphorus cycling were significantly enhanced under N enrichment in both the wheat and maize seasons, and higher enzyme activities were noted in the high N addition treatment than in the low N addition treatment. A linear increase in fungal abundance with the N addition gradient was observed in the wheat season, whereas the fungal abundance increased and then decreased in the maize season. The bacterial abundance showed an increased and then decreased trend in response to the N addition gradient in both the wheat and maize crop seasons. Moreover, the partial least squares path model (PLS-PM) analysis showed that soil pH and soil organic carbon (SOC) were the most important soil variables, causing shifts in the soil bacteria. Furthermore, compared with the N-cycling enzymes, the C-cycling enzymes were significantly affected by the soil pH and SOC. Taken together, these results suggest that the effect of N addition on enzyme activities was consistent in both crop seasons, while the effects on MBN and microbial community composition to N addition were highly variable in the two crop seasons. Moreover, N fertilization-induced changes in the soil chemical properties such as soil acidity and SOC played a substantial role in shaping the microbial community.

Involvement of macrophage-derived exosomes in abdominal aortic aneurysms development.

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) is characterized by infiltration of inflammatory cells, extracellular matrix (ECM) degradation, and dysfunction of vascular smooth muscle cells (VSMCs). Recent studies reported that exosomes mediate intercellular communication and are involved in different diseases. Whether exosomes play a role in AAA is poorly understood. Hence, this study evaluated the function of exosomes in AAA development. METHODS: The presence of exosomes in human and calcium phosphate (CaPO4)-induced AAA tissues was determined by immunofluorescence staining of CD63 and Alix. GW4869, an inhibitor of exosome biogenesis, was intraperitoneally injected into CaPO4-induced AAA tissues to evaluate the effects of exosomal inhibition on AAA development. To explore the underlying mechanisms, the human monocytic cell line THP-1 was differentiated into macrophages, and exosomes were collected from macrophages. VSMCs were treated with macrophage-derived exosomes, and the expression of matrix metalloproteinase-2 (MMP-2) was evaluated. The activation of mitogen-activated protein kinases (MAPKs) pathways was also investigated in vitro and in vivo. RESULTS: Exosomes were detected in the adventitia of aneurysmal tissues obtained from humans and mice. They were mainly expressed in clusters of macrophages. Intraperitoneal injection of GW4869 for two weeks significantly attenuated the progression of CaPO4-induced AAA, preserved elastin integrity and decreased MMP-2 expression. Similarly, administration of GW4869 suppressed the systemic and aneurysmal exosome generation. In vitro, treatment with macrophage-derived exosomes elevated MMP-2 expression in human VSMCs, while pre-treatment with GW4869 abolished these effects. It was also found that JNK and p38 pathways mediated the production of MMP-2 in VSMCs following treatment with macrophage-derived exosomes. CONCLUSIONS: This study suggests that exosomes derived from macrophages are involved in the pathogenesis of AAA. Macrophage-derived exosomes trigger MMP-2 expression in VSMC via JNK and p38 pathways. GW4869 supplementation attenuates CaPO4-induced AAA in mice.