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Background: Atherosclerotic cardiovascular diseases remain the leading cause of mortality in diabetic patients, with endothelial cell (EC) dysfunction serving as the initiating step of atherosclerosis, which is exacerbated in diabetes. Krüppel-like factor 11 (KLF11), known for its missense mutations leading to the development of diabetes in humans, has also been identified as a novel protector of vascular homeostasis. However, its role in diabetic atherosclerosis remains unexplored. Methods: Diabetic atherosclerosis was induced in both EC-specific KLF11 transgenic and knockout mice in the Ldlr−/− background by feeding a diabetogenic diet with cholesterol (DDC). Single-cell RNA sequencing (scRNA-seq) was utilized to profile EC dysfunction in diabetic atherosclerosis. Additionally, gain- and loss-of-function experiments were conducted to investigate the role of KLF11 in hyperglycemia-induced endothelial cell dysfunction. Results: We found that endothelial KLF11 deficiency significantly accelerates atherogenesis under diabetic conditions, whereas KLF11 overexpression remarkably inhibits it. scRNA-seq profiling demonstrates that loss of KLF11 increases endothelial-to-mesenchymal transition (EndMT) during atherogenesis under diabetic conditions. Utilizing gain- and loss-of-function approaches, our in vitro study reveals that KLF11 significantly inhibits EC inflammatory activation and TXNIP-induced EC oxidative stress, as well as Notch1/Snail-mediated EndMT under high glucose exposure. Conclusion: Our study demonstrates that endothelial KLF11 is an endogenous protective factor against diabetic atherosclerosis. These findings indicate that manipulating KLF11 could be a promising approach for developing novel therapies for diabetes-related cardiovascular complications. [ABSTRACT FROM AUTHOR]

Cardiovascular plaques result from atherosclerosis. Autopsy investigations of unnatural deaths provide atherosclerosis research. A Central European cohort was studied in a cross-sectional study to determine the origin of atherosclerosis and the link between arterial status and pathobiological variables. This study incorporated 3400 autopsy reports (n = 2318 men; aged 0─96 years; 1928─2010) of persons who died by unnatural causes (suicide, homicide, accident). Age, sex, BMI, abdominal fat thickness, and arterial status of six vascular areas were gathered. The arterial state was divided into five subgroups according to its status. BMI declined from 22.82 kg/m2 in 1931 to 18.43 kg/m2 in 1947, then increased to 27.88 kg/m2 in 2005. Atherosclerotic degeneration begins in the abdominal aorta, then the thoracic, coronary, carotid, ascending, and cerebral arteries. All blood arteries deteriorated faster in men than women until 55. Abdominal aorta damage was the fastest in both sexes. Age is the biggest predictor of atherosclerosis, followed by sex, overweight, and abdominal thickness, according to logistic regression. This is the largest Central European autopsy investigation of six vascular areas. Both sexes develop atherosclerosis in the abdominal aorta in the first decade of life. Being overweight increases the risk. The findings of this study aid healthcare providers in personalized therapy. [ABSTRACT FROM AUTHOR]

Cerebral revascularization for the treatment of atherosclerotic steno-occlusive disease (ASOD) was found to have no benefit compared with medical treatment. However, there is also criticism that with sufficiently long-term follow-up, a crossover might emerge demonstrating the advantages of surgery. Therefore, we examined the long-term outcome of cerebral revascularization performed on patients with carefully selected ASOD at our center. Patients undergoing bypass surgery for non-moyamoya ischemic disease were retrospectively identified. The inclusion criteria were symptomatic ASOD with hemodynamic insufficiency, follow-up of more than 5 years, and stroke or surgical complications during follow-up. The clinical course and radiological findings were investigated. Poor outcomes were predicted using machine learning (ML) models, and Shapley additive explanation (SHAP) values and feature importance of each model were analyzed. A total of 109 patients were included from 2007 to 2018. The 30-day risk of any stroke or death was 6.4% (7/109). The risk of ipsilateral ischemic stroke during median follow-up of 116 months was 7.3% (8/109). The SHAP values showed that previously and empirically known stroke risk factors exert a relatively consistent effect on the prediction of models. The number of lesions with stenosis > 50% (odds ratio [OR] 5.77), age (OR 1.13), and coronary artery disease (OR 5.73) were consistent risk factors for poor outcome. We demonstrated an acceptable long-term outcome of cerebral revascularization surgery for patients with hemodynamically insufficient and symptomatic ASOD. Multicenter studies are encouraged to predict poor outcomes and suitable patients with large numbers of quantitative and qualitative data. [ABSTRACT FROM AUTHOR]

Objective: This research is aimed at unravelling the intricate relationship between transient receptor potential vanilloid 6 (TRPV6), protein kinase A (PKA), uncoupling protein 2 (UCP2), and atherosclerosis. By shedding light on the role of the TRPV6/PKA/UCP2 pathway in inhibiting inflammatory response and cell apoptosis in coronary atherosclerotic plaques, this study provides valuable insights into potential therapeutic targets for treating coronary artery disease (CAD). Methods: We established animal and cell models of atherosclerosis. The expression of TRPV6 was measured using immunohistochemistry and immunofluorescence. Cytokine levels were detected by enzyme‐linked immunosorbent assay (ELISA). Cell viability and apoptosis ratio were measured using cell counting kit‐8 (CCK‐8) and flow cytometry. The binding relationship between TRPV6 and PKA was validated using chromatin immunoprecipitation (CHIP) and coimmunoprecipitation (CoIP). Finally, the expression of the TRPV6/PKA/UCP2 signaling pathway and apoptosis‐related factors was detected using western blot (WB) and quantitative real‐time polymerase chain reaction (qRT‐PCR). Results: TRPV6 was significantly decreased in atherosclerosis mouse and cell model. CHIP and CoIP assays indicated that TRPV6 binds to PKA and positively regulated its expression in oxidized low‐density lipoprotein (ox‐LDL)–treated human umbilical vein endothelial cells (HUVECs). Overexpression of TRPV6 significantly increased cell viability and inhibited apoptosis, whereas silencing TRPV6 had the opposite effect. Additionally, the overexpression of TRPV6 remarkably declined the expression of tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), and interleukin‐1 beta (IL‐1β). However, after silencing PKA, this effect was partially reversed, the cell viability and inflammatory response remarkably enhanced, and apoptosis significantly declined in oe‐TRPV6 + si‐PKA group. Conclusions: In summary, our study demonstrated that TRPV6 inhibited apoptosis and inflammatory response in the atherosclerosis cell model through the regulation of the PKA/UCP2 pathway. [ABSTRACT FROM AUTHOR]

The risk of atherosclerotic cardiovascular diseases (ASCVDs) can be reduced by lowering low-density lipoprotein cholesterol (LDL-C) concentrations. Nevertheless, ASCVDs still cause most deaths worldwide. Here, we discuss the prevention of ASCVD and the event risk with a focus on heart-healthy diets, i.e., low intakes of saturated and trans-fatty acids and cholesterol, and high intakes of unsaturated fatty acids, viscous fibre, and dietary phytostanols as fatty acid esters, according to international dyslipidaemia treatment guidelines. Calculations based on both FINRISK and Cholesterol Treatment Trialists' Collaborators regression equations indicate that heart-healthy diets combined with phytostanol ester reduce LDL-C concentrations to such an extent that the 10-year estimated reduction in the incidence of coronary artery disease would be 23%. This information can be used, in particular, to prevent the development of subclinical atherosclerosis in healthy middle-aged populations and the progression of atherosclerosis to ASCVD. The outcome of simple and feasible dietary changes, and, when needed, combined with statins, can be significant: reduced mortality, an increased number of healthy life-years, and reduced healthcare costs. [ABSTRACT FROM AUTHOR]

Introduction: Atherosclerosis (AS) is considered the underlying cause of many diseases, particularly cardiovascular and cerebrovascular diseases. Inulin, a type of fructan, has shown potential in improving atherosclerosis, although there are conflicting findings. It is hypothesized that the polymerization degree of inulin may largely influence its therapeutic effectiveness. Therefore, this study aimed to investigate the effects and mechanisms of short-chain and long-chain inulin in AS. Methods: ApoE−/− mice fed a high fat diet (HFD) were used to establish an atherosclerosis model. These mice received daily oral administration of either short-chain or long-chain inulin for 12 weeks. Plasma lipid metabolism-related indices were measured using biochemical analysis, and plasma immunological indices were analyzed via ELISA. The aorta, aortic root regions, liver tissue, adipose tissue, and colon tissue were examined through various staining techniques, including ORO staining, hematoxylin and eosin staining, Alcian blue staining, and immunofluorescent or immunohistochemical assays. Microbiome analysis was conducted in the cecal content. Results: The results indicated that both short-chain and long-chain inulin substantially reduced the formation of atherosclerotic plaques. Inulin also improved plasma lipid concentrations and hepatic lipid metabolism, and partially alleviated both localized (atherosclerotic lesions) and systemic inflammation. Short-chain inulin was more effective than long-chain inulin in reducing atherosclerotic plaques formation, enhancing lipid metabolism and reducing inflammation. Additionally, both types of inulin showed similar effectiveness in enhancing intestinal epithelial barrier integrity, gut microbiota composition and functionality. Conclusion: These findings suggest that inulin has a protective role against atherosclerosis by enhancing lipid metabolism, reducing inflammation, and improving intestinal barrier and gut microbiota. As a dietary intervention, shortchain inulin is more effective than long-chain inulin, offering clinical implications for using inulin as a therapeutic agent for atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a significant public health concern associated with a high prevalence of carotid plaques, which are indicators of atherosclerosis and predictors of adverse cardiovascular outcomes. Inflammation is a hallmark of CKD, contributing to both renal dysfunction and cardiovascular complications. This study aims to investigate the association between inflammatory markers—systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), aggregate inflammatory status index (AISI), monocyte to high-density lipoprotein cholesterol ratio (MHR), neutrophil to high-density lipoprotein cholesterol ratio (NHR), neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR)—and carotid plaques in CKD patients, and to explore the potential mediating role of estimated glomerular filtration rate (eGFR) in this relationship. Methods: A cross-sectional analysis was conducted on patients admitted to the Division of Nephrology between January 2023 and June 2023. The primary endpoint was the presence of carotid plaques assessed using ultrasound imaging. Multivariable logistic regression models were used to examine the associations between inflammatory markers and carotid plaques, and trend tests were performed to evaluate the trending association of carotid plaques risk and inflammatory markers in tertiles. Restricted cubic spline (RCS) analysis was used to assess potential non-linear relationships, and subgroup analyses were conducted to examine consistency across different strata. Mediation analysis was performed to explore the role of eGFR. Results: Of the 609 participants, 387 were included in the final analysis after applying exclusion criteria. Elevated levels of LnSIRI (OR = 1.87, 95% CI = 1.25–2.80), LnSII (OR = 1.67, 95% CI = 1.09–2.56), LnAISI (OR = 1.70, 95% CI = 1.22–2.37), LnMHR (OR = 1.94, 95% CI = 1.15–3.26), LnNHR (OR = 1.82, 95% CI = 1.10–3.02), and LnMLR (OR = 2.26, 95% CI = 1.18–4.34) were significantly associated with the presence of carotid plaques. There were significant trends for increasing tertiles of SIRI, AISI, MHR and NHR. RCS analysis showed no significant non-linear associations. Subgroup analyses indicated similar associations across most strata. eGFR partially mediated these relationships, with proportions mediated ranging from 14.7 to 17.5%. Conclusions: Inflammatory markers are significantly associated with carotid plaques in CKD patients, with eGFR playing a partial mediating role. These findings highlighted the importance of managing inflammation and maintaining renal function to mitigate the risk of atherosclerosis in CKD patients. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Insomnia (ISM) is one of the non-traditional drivers of atherosclerosis (AS) and an important risk factor for AS-related cardiovascular disease. Our study aimed to explore the shared pathways and diagnostic biomarkers of ISM-related AS using integrated bioinformatics analysis. Methods: We download the datasets from the Gene Expression Omnibus database and the GeneCards database. Weighted gene co-expression network analysis and gene differential expression analysis were applied to screen the ASrelated gene set. The shared genes of ISM and AS were obtained by intersecting with ISM-related genes. Subsequently, candidate diagnostic biomarkers were identified by constructing protein-protein interaction networks and machine learning algorithms, and a nomogram was constructed. Moreover, to explore potential mechanisms, a comprehensive analysis of shared genes was carried out, including enrichment analysis, protein interactions, immune cell infiltration, and single-cell sequencing analysis. Results: We successfully screened 61 genes shared by ISM and AS, of which 3 genes (IL10RA, CCR1, and SPI1) were identified as diagnostic biomarkers. A nomogram with excellent predictive value was constructed (the area under curve of the model constructed by the biomarkers was 0.931, and the validation set was 0.745). In addition, the shared genes were mainly enriched in immune and inflammatory response regulation pathways. The biomarkers were associated with a variety of immune cells, especially myeloid immune cells. Conclusion: We constructed a diagnostic nomogram based on IL10RA, CCR1, and SPI1 and explored the inflammatory-immune mechanisms, which indicated new insights for early diagnosis and treatment of ISM-related AS. [ABSTRACT FROM AUTHOR]

Background: Endovascular recanalization is a feasible option for treating symptomatic non-acute middle cerebral artery occlusion (MCAO) patients. Hence, we aimed to establish a new angiographic scoring to grade the recanalization difficulty of MCAO to determine the suitable patients for endovascular treatment. Methods: We retrospectively analyzed a total of 113 consecutive recurrent symptomatic non-acute MCAO patients who underwent endovascular recanalization from July 2015 to August 2021 in four Chinese comprehensive stroke centers. All patients were reappraised using a new angiographic scoring based on the stump morphology, the MCA occlusion length, MCA bend, and the distal vascular bed of MCAO. We used the final results to establish the patients' outcomes. Results: The total successful recanalization and perioperative complication rates were 83.2% (94/113) and 15.9% (18/113), respectively. No deaths occurred within 30 days. Moreover, 96.9, 90, 87.5, 52.6, and 50% of the patients achieved recanalization with scores of 0, 1, 2, 3, and 4 (p < 0.001), respectively. However, the perioperative complication rate showed the opposite trend. (3.1% vs. 7.5% vs. 6.3% vs. 52.6% vs. 50%; p < 0.001). The median time of successful microwire crossing of the occlusion lesion (TMO) in the score 0 group was shorter than the other groups (2 min, 9 min, 8.5 min, 14 min, and 20 min; p < 0.001). When a score of 2 was used as the optimal cut-off point, the sensitivity and specificity were 86.2 and 63.2%, respectively. Conclusion: The new angiographic scoring can effectively predict the successful recanalization rate, perioperative complication rate, and TMO of endovascular recanalization for non-acute MCAO. It can also be used as an effective clinical evaluation tool to determine the suitable non-acute MCAO patients for recanalization, especially with a score = 2. [ABSTRACT FROM AUTHOR]

Curcumin, a polyphenolic compound derived from the widely used spice Curcuma longa, has shown anti-atherosclerotic effects in animal models and cultured vascular cells. Inflammation is a major contributor to atherosclerosis development and progression. We previously reported that the induction of the proinflammatory molecule TRAF3IP2 (TRAF3 Interacting Protein 2) or inhibition of the matrix metallopeptidase (MMP) regulator RECK (REversion Inducing Cysteine Rich Protein with Kazal Motifs) contributes to pro-oxidant, proinflammatory, pro-mitogenic and pro-migratory effects in response to external stimuli in vascular smooth muscle cells. Here we hypothesized that EF24, a curcumin analog with a better bioavailability and bioactivity profile, reverses interleukin (IL)-18-induced TRAF3IP2 induction, RECK suppression and the proinflammatory phenotype of primary human aortic smooth muscle cells (ASMC). The exposure of ASMC to functionally active recombinant human IL-18 (10 ng/mL) upregulated TRAF3IP2 mRNA and protein expression, but markedly suppressed RECK in a time-dependent manner. Further investigations revealed that IL-18 inhibited both miR-30a and miR-342 in a p38 MAPK- and JNK-dependent manner, and while miR-30a mimic blunted IL-18-induced TRAF3IP2 expression, miR-342 mimic restored RECK expression. Further, IL-18 induced ASMC migration, proliferation and proinflammatory phenotype switching, and these effects were attenuated by TRAF3IP2 silencing, and the forced expression of RECK or EF24. Together, these results suggest that the curcumin analog EF24, either alone or as an adjunctive therapy, has the potential to delay the development and progression of atherosclerosis and other vascular inflammatory and proliferative diseases by differentially regulating TRAF3IP2 and RECK expression in ASMC. [ABSTRACT FROM AUTHOR]

(1) Background: In 2022, the World Stroke Organization said there were more than 12.2 million new cases of stroke each year, between all ages and sexes. Six and a half million people die each year from stroke. Ischemic stroke accounts for 7.6 million (62%) cases, with 3.3 million (51%) deaths. Stroke is mainly linked to the atherosclerosis of a large artery. (2) Objective: Since the carotid artery directly supplies the brain, we used age-dependent mechanical mapping on the healthy common carotid artery (CCA) with the aim of being able to predict and thus potentially prevent ischemic stroke. (3) Methods: We assessed the CCA stiffness of 95 healthy control (CTL) females (2.23–39.46 years) and 107 healthy CTL males (2.85–40 years). Cine-loops of B-mode CCA data were digitally recorded with conventional medical ultrasound devices. Arterial wall elastic moduli were estimated offline using a proprietary non-invasive imaging-based biomarker algorithm (ImBioMark). Statistical analyzes were carried out with Excel software. (4) Results: Females showed a linear regression profile of CCA elastic moduli ranging from 41 ± 2 kPa to 54 ± 17 kPa (R2 = 0.88), while males showed one ranging from 38 ± 5 kPa to 63 ± 22 kPa (R2 = 0.83). For qualitative and quantitative illustrations, the elastic modulus data of CTLs were compared with those of subjects with Kawasaki disease and subjects born prematurely, respectively. (5) Conclusions: This study introduced some fundamental features of the mechanical evolution of the CCA as a function of age (2–40 years). Since atherosclerotic arteriopathy starts early in life, this gives the ability to predict risks of stroke and other cardiovascular diseases with the possibility of applying a more comprehensive range of potential preventive measures early in life. This is consistent with preventive medicine objectives which aim to be more predictive to implement pre-emptive measures as opposed to diagnostic and curative approaches. [ABSTRACT FROM AUTHOR]

Background: We aimed to explore the predictive role of soluble urokinase plasminogen activator receptor (suPAR) in patients undergoing coronary angiography by systematically evaluating its association with adverse cardiovascular events at 10 years follow-up. Methods: The KORONEF study was a single-center, observational, prospective study with 492 subjects included. In the multivariable Cox regression model, we checked the impact of suPAR, neutrophil elastase, myeloperoxidase, and DNase 1 on long-term outcomes. Results: The mean study population age was 64.4 ± 9.9 years, and there were 37.2% women. We divided the population into tertiles of suPAR levels (T1 0.793–2.135 ng/mL; T2 2.136–2.868 ng/mL; and T3 2.872–8.677 ng/mL). Patients with higher suPAR concentrations were more often females (tertile 1 vs. tertile 3: 27.4% vs. 50.6%, p < 0.001) and older age (60.8 ± 8.7 years vs. 68.8 ± 9.5 years, p < 0.001). They also characterized higher incidence of diabetes (17.7% vs. 38.0%, p < 0.001), previous myocardial infarction (22% vs. 44.8%, p < 0.001), and chronic kidney disease (3% vs. 18.4%, p < 0.001), but lower incidence of dyslipidemia (54.3% vs. 35.6%). The 10-year all-cause death rates were 14.6% vs. 34.1%, HR 2.68, 95% CI 1.66–4.33, p < 0.001 for tertile 2, and 14.6% vs. 39.9%, HR 3.24, 95% CI 2.03–5.17, p < 0.001 for tertile 3. The optimal cut-off suPAR value of 2.39 ng/mL provided a sensitivity of 66.9% and a specificity of 54.6% in predicting all-cause death. Conclusions: The association of elevated suPAR with increased mortality risk suggests its potential relevance in predicting long-term outcomes and may help inform more individualized management strategies for high-risk patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: Hypertension increases the risk of developing atherosclerosis and arterial stiffness, with secondarily enhanced wall stress pressure that damages the artery wall. The coexistence of atherosclerosis and hypertension leads to artery stenosis and microvascular angiopathies, during which the intravascular mechanical hemolysis of red blood cells (RBCs) occurs, leading to increased platelet activation, dysfunction of the endothelium and smooth muscle cells due to a decrease in nitric oxide, and the direct harmful effects of hemoglobin and iron released from the red blood cells. This study analyzed the impact of hypertension and physical exercise on the risk of hemolysis in the left coronary artery. Methods: To analyze many different cases and consider the decrease in flow through narrowed arteries, a flow model was adopted that considered hydraulic resistance in the distal section, which depended on the conditions of hypertension and exercise. The commercial ANSYS Fluent 2023R2 software supplemented with user-defined functions was used for the simulation. CFD simulations were performed and compared with the FSI simulation results. Results: The differences obtained between the FSI and CFD simulations were negligible, which allowed the continuation of analyses based only on CFD simulations. The drops in pressure and the risk of hemolysis increased dramatically with increased flow associated with increased exercise. A relationship was observed between the increase in blood pressure and hypertension, but in this case, the increase in blood pressure dropped, and the risk of hemolysis was not so substantial. However, by far, the case of increased physical activity with hypertension had the highest risk of hemolysis, which is associated with an increased risk of clot formation that can block distal arteries and lead to myocardial hypoxia. Conclusions: The influence of hypertension and increased physical exercise on the increased risk of hemolysis has been demonstrated. [ABSTRACT FROM AUTHOR]

Objectives: This study examined the association between sarcopenic obesity and arterial stiffness using bioelectrical impedance analysis (BIA). Methods: This retrospective cross-sectional study included 20,601 Korean adults from January 2016 to December 2023. Sarcopenia was defined as height-adjusted appendicular skeletal muscle mass [(ASM/height2) <5.7 in women and <7.0 in men] using BIA. Obesity was defined by body mass index or waist circumference. Arterial stiffness was assessed by measuring brachial-ankle pulse wave velocity (baPWV). The participants were categorized into four groups: normal, sarcopenia, obesity, and sarcopenic obesity. The baPWV values were compared among the four groups to investigate the association between sarcopenic obesity and arterial stiffness using adjusted multivariate analyses. Results: The mean baPWV of the sarcopenic obesity group was higher (p < 0.001) than that of the other groups. The odds ratio for having high baPWV (>1800 cm/s) in the sarcopenic obesity group was 2.40 (95% CI, 1.07–5.38) after adjusting for age, sex, exercise, smoking, heavy alcohol consumption, hypertension, and dyslipidemia. Conclusions: Sarcopenic obesity was independently associated with increased arterial stiffness. [ABSTRACT FROM AUTHOR]

Background/Objectives: The multifactorial nature of atherosclerotic cardiovascular disease (ASCVD) implicates genetic, environmental, and dietary habits. Antioxidants found in foods have garnered attention for their potential role in mitigating ASCVD risk by combating oxidative stress. This study seeks to confirm the findings of previous research through a large-scale cross-sectional analysis performed in a unique population with Korea National Health and Nutrition Examination Survey data to explore the association between the composite dietary antioxidant index (CDAI) and ASCVD prevalence among middle- and old-aged individuals in South Korea. Methods: This study includes data from 2016 to 2021. The CDAI was calculated based on nutrition intake, including zinc, beta-carotene, vitamin A, vitamin C, vitamin E, and docosahexaenoic acid. This cross-sectional analysis explored the relationship between the CDAI and ASCVD after adjusting for relevant covariates. Logistic regression models were employed, and subgroup analyses by sex were conducted to discern sex-specific effects. Results: A total of 19,818 individuals were analyzed, with 7.0% of them diagnosed with ASCVD. CDAI distribution and antioxidant analyses revealed higher CDAI levels in non-ASCVD individuals. Standardized antioxidant values increased across CDAI quartiles. Initially, a significant association (odds ratio [95% confidence interval]: 0.96 [0.94–0.99]) was found between the CDAI and ASCVD, which was attenuated after adjusting for covariates (1.0 [0.98–1.02]). Subgroup analyses by sex showed nuanced associations, with the CDAI potentially reducing the risk of ASCVD in men (0.71 [0.53–0.94]) while increasing it in women (1.4 [1.01–1.95]). Conclusions: This study provides valuable insights into the association between dietary antioxidant intake and the risk of ASCVD, highlighting sex-specific differences. [ABSTRACT FROM AUTHOR]

Inflammation plays a crucial role in atherosclerosis and nonalcoholic fatty liver disease (NAFLD). We previously engineered a recombinant Lactococcus lactis strain expressing the Ling-Zhi immunomodulatory protein (L. lactis-LZ8). This study investigated the anti-atherosclerotic effects of L. lactis-LZ8 in rabbits fed a high-fat diet (HFD). Changes in body weight, serum lipid profiles, and liver function were monitored. The aorta and liver tissues were analyzed for gross pathology and histopathology. Eight-week administration of L. lactis-LZ8 with HFD ameliorated atherosclerosis by downregulating protein and gene expression associated with lipid metabolism and inflammation in the aortas. The rabbits receiving L. lactis-LZ8 exhibited a significant dose-dependent reduction in hepatic fat accumulation. RNA sequencing of the livers revealed that inflammatory genes in the L. lactis-LZ8 groups were downregulated compared to the HFD group. Disease ontology enrichment analysis indicated that these genes were involved in atherosclerosis. Gene set enrichment analysis plots revealed significant enrichment in the gene sets related to cholesterol homeostasis. CIBERSORT immune cell fraction analysis indicated significant infiltration by regulatory T cells, CD8+ T cells, activated dendritic cells, and natural killer cells in the L. lactis-LZ8 group. Our studies underscore LZ8's role in precision nutrition, providing a potential solution to the current challenges in modifying atherosclerosis and NAFLD. [ABSTRACT FROM AUTHOR]

In rheumatoid arthritis (RA), the risk of cardiovascular death is 50% higher compared to the general population. This increased risk is partly due to the systemic inflammation characteristic of RA and changes in the lipoprotein profiles. This study investigated plasma lipid levels, lipid ratios, and the composition and functionality of high-density lipoprotein (HDL) in control individuals and RA subjects based on the disease's inflammatory score (DAS28). This study included 50 control (CTR) individuals and 56 subjects with RA, divided into remission/low-activity disease (DAS28 < 3.2; n = 13) and active disease (DAS28 ≥ 3.2; n = 43). Plasma lipids (total cholesterol, TC; triglycerides, TG) and the HDL composition (TC; TG; phospholipids, PL) were determined using enzymatic methods; apolipoprotein B (apoB) and apoA-1 were measured by immunoturbidimetry. HDL-mediated cholesterol efflux and anti-inflammatory activity were assessed in bone marrow-derived macrophages. Comparisons were made using the Mann–Whitney test, and binary logistic regression was used to identify the predictors of active RA. A p-value < 0.05 was considered significant. TC, HDLc, and the TC/apoB ratio were higher in RA subjects compared to the CTR group. Subjects with active disease exhibited higher levels of TG and the TG/HDLc ratio and lower levels of HDLc, the TG/apoB ratio, TC, and apoA-1 in HDL particles compared to those with remission/low-activity RA. Increased levels of HDLc [odds ratio (OR) 0.931, 95% CI = 0.882–0.984], TC/apoB (OR 0.314, 95% CI = 0.126–0.78), HDL content in TC (OR 0.912, 95% CI = 0.853–0.976), PL (OR 0.973, 95% CI = 0.947–1.000), and apoA-1 (OR 0.932, 95% CI = 0.882–0.985) were associated with a decreased risk of active disease, but BMI (OR 1.169, 95% CI = 1.004–1.360) and TG (OR 1.031, 95% CI = 1.005–1.057) were positively associated with active disease. A reduction in HDL-mediated cholesterol efflux increased the OR for active RA by 26.2%. The plasma levels of HDLc, along with the composition and functionality of HDL, influence the inflammatory score in RA and may affect the development of cardiovascular disease. [ABSTRACT FROM AUTHOR]

The molecular mechanisms by which cardiovascular risk factors promote the development of atherosclerosis are poorly understood. We have recently shown that genetic ablation of myeloid glycogen synthase kinase (GSK)-3α attenuates atherosclerotic lesion development in low-density lipoprotein receptor-deficient (Ldlr−/−) mice. However, the precise contributions of GSK3α/β in atherogenesis are not known. The aim of this study is to investigate the effect of GSK3α and/or β deficiency on lesional inflammation and plaque vascularization. Five-week-old female Ldlr−/− mice were fed a high-fat diet for 10 weeks to establish atherosclerotic lesions. Mice were harvested at 15 weeks of age and atherosclerotic lesions were characterized. The results indicate that, in addition to significantly reducing plaque volume, GSK3α-deficiency decreases inflammation, reduces vasa vasorum density at the aortic sinus, and reduces plasma c-reactive protein (CRP) levels. GSK3β-deficiency is associated with decreased plasma CRP levels but does not affect lesional inflammation or vascularization. These results suggest GSK3α may be an applicable target for the development of novel anti-atherogenic therapies. [ABSTRACT FROM AUTHOR]

This narrative review aims specifically to explore the relationship between tobacco exposure and systemic sclerosis (SSc), idiopathic inflammatory myositis (IIM), and systemic lupus erythematosus (SLE). Relevant articles were obtained by searching key terms such as "tobacco," "smoking," "scleroderma," "myositis," "lupus," and "Sjögren's" in PubMed and Google Scholar databases. The selected articles ranged from the years 2010 to 2023. Inclusion criteria were based on the relevance and contribution to the field of study. Systemic sclerosis is a complex condition involving multiple immune cell lines that can be influenced by tobacco. However, the existing literature does not provide sufficient evidence to support an increased risk of SSc in smokers or the impact on treatment options. Cigarette smoking does increase the risk of skin ulcerations in SSc patients. In addition, cigarette smoking has been associated with IIM through genetic and molecular mechanisms. Smokers with dermatomyositis or polymyositis are at an elevated risk of atherosclerosis and interstitial lung disease. Similarly, smoking in patients with SLE increases the risk of organ damage, thrombosis, and disease severity compared with non-smokers. Smokers with SLE also have more difficulty in controlling disease flares compared with non-smokers. Tobacco exposure can lead to secondary complications in patients with IIM and SLE, although the course of treatment may not differ significantly. No definitive conclusions can be drawn to the clear relationship between tobacco smoking and Sjögren's's syndrome. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of bufrudin on lipid metabolism and vascular plaques in ApoE-/- mice with atherosclerosis. Methods A total of 24 male ApoE-/- mice fed with high-fat diet were randomly divided into the model group, the high-dose and the low-dose groups of bufrudin, and the simvastatin positive group, with six mice in each group. Another six C57BL/6J mice were taken as the blank control group and fed with normal diet. After continuous administration for eight weeks. the blood lipid level was detected after the last administration, and the pathological changes of aortic vessels were observed by HE staining and Masson staining. Immunohistochemical staining was used to observe the effects of bufrudin on proliferating Cell nuclear antigen (PCNA) and caspase-3 protein in aortic atherosclerotic plaques of mice. Results Compared with the blank control group, the levels of serum total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) in the model group were significantly increased, and the level of high density lipoprotein cholesterol (HDL-C) was significantly decreased, and differences were statistically significant (P<0.01). Compared with the model group, the levels of serum TC, TG and LDL-C in the high-dose and lowdose groups of bufrudin were significantly decreased, and the level of HDL-C was significantly increased, the differences were statistically significant (P<0.01). Masson staining showed that compared with the model group, the collagen content in the vascular plaque of mice in the high and low dose groups of bufrudin was significantly increased, and the difference was statistically significant (P < 0.01) The results of immunohistochemical staining showed that compared with the blank control group, the expression of PCNA protein in the aortic atherosclerotic plaque of the model group was significantly down-regulated, and the expression of caspase-3 protein was significantly up-regulated, the differences were statistically significant (P < 0.01) Compared with the model group. the expression of PCNA protein in the aortic atherosclerotic plaque of the mice in the bufrudin group was significantly up-regulated, and the expression of caspase-3 protein in the bufrudin high-dose group was significantly down-regulated, the differences were statistically significant (P < 0.05) Conclusion Bufrudin can inhibit the development of atherosclerosis by reducing serum lipid levels in ApoE mice, delaying smooth muscle cell apoptosis, and stabilizing vascular plaques. [ABSTRACT FROM AUTHOR]

ABSTRACT The relationships between the atherogenic index of plasma (AIP) and carotid–femoral pulse wave velocity (cfPWV) in adults were investigated. A total of 1398 subjects were included according to the inclusion criteria. Demographic data, medical history, and biochemical indicators were collected. The cfPWV was measured using the Complior Analyse device. AIP was calculated using the following formula: AIP = log (triglycerides/high‐density lipoprotein cholesterol). Correlation analysis, multiple linear regression, and logistic regression were performed to explore the relationships between AIP and cfPWV. Compared to the cfPWV normal group, the cfPWV elevated group had a higher level of AIP (p < 0.05). In all subjects, mild‐to‐moderate correlations were found between AIP and cfPWV (p < 0.05). Stepwise multiple linear regression analysis revealed that AIP was an independent factor associated with cfPWV (β = 0.156, p < 0.05). Logistic regression analysis indicated that the prevalence of cfPWV ≥ 10 m/s increased with the rise of AIP (OR = 18.291, p < 0.05). The ROC curve analysis showed that the area under the curve for AIP was 0.697. The critical point for AIP was determined as 0.00 by the Youden index (sensitivity of 76.2% and specificity of 54.3%). Stepwise multiple linear regression analysis showed that in the young and middle‐aged group with normal cfPWV, AIP was an independent factor associated with cfPWV (p < 0.05). In adults, AIP is an independent factor associated with an increased cfPWV. When AIP > 0.00, it has a certain predictive value in the screening of atherosclerosis. [ABSTRACT FROM AUTHOR]

Atherosclerosis serves as the primary catalyst for numerous cardiovascular diseases. Growing evidence suggests that the immune response is involved in every stage of atherosclerotic plaque evolution. Rapid, but not specific, innate immune arms, including neutrophils, monocytes/macrophages, dendritic cells (DCs) and other innate immune cells, as well as pattern-recognition receptors and various inflammatory mediators, contribute to atherogenesis. The specific adaptive immune response, governed by T cells and B cells, antibodies, and immunomodulatory cytokines potently regulates disease activity and progression. In the inflammatory microenvironment, the heterogeneity of leukocyte subpopulations plays a very important regulatory role in plaque evolution. With advances in experimental techniques, the fine mechanisms of immune system involvement in atherosclerotic plaque evolution are becoming known. In this review, we examine the critical immune responses involved in atherosclerotic plaque evolution, in particular, looking at atherosclerosis from the perspective of evolutionary immunobiology. A comprehensive understanding of the interplay between plaque evolution and plaque immunity provides clues for strategically combating atherosclerosis. [ABSTRACT FROM AUTHOR]

Background and Aims Vascular smooth muscle cell (VSMC) senescence is crucial for the development of atherosclerosis, characterized by metabolic abnormalities. Tumour necrosis factor receptor-associated protein 1 (TRAP1), a metabolic regulator associated with ageing, might be implicated in atherosclerosis. As the role of TRAP1 in atherosclerosis remains elusive, this study aimed to examine the function of TRAP1 in VSMC senescence and atherosclerosis. Methods TRAP1 expression was measured in the aortic tissues of patients and mice with atherosclerosis using western blot and RT–qPCR. Senescent VSMC models were established by oncogenic Ras, and cellular senescence was evaluated by measuring senescence-associated β-galactosidase expression and other senescence markers. Chromatin immunoprecipitation (ChIP) analysis was performed to explore the potential role of TRAP1 in atherosclerosis. Results VSMC-specific TRAP1 deficiency mitigated VSMC senescence and atherosclerosis via metabolic reprogramming. Mechanistically, TRAP1 significantly increased aerobic glycolysis, leading to elevated lactate production. Accumulated lactate promoted histone H4 lysine 12 lactylation (H4K12la) by down-regulating the unique histone lysine delactylase HDAC3. H4K12la was enriched in the senescence-associated secretory phenotype (SASP) promoter, activating SASP transcription and exacerbating VSMC senescence. In VSMC-specific Trap1 knockout Apoe KO mice (Apoe KO Trap1 SMCKO), the plaque area, senescence markers, H4K12la, and SASP were reduced. Additionally, pharmacological inhibition and proteolysis-targeting chimera (PROTAC)-mediated TRAP1 degradation effectively attenuated atherosclerosis in vivo. Conclusions This study reveals a novel mechanism by which mitonuclear communication orchestrates gene expression in VSMC senescence and atherosclerosis. TRAP1-mediated metabolic reprogramming increases lactate-dependent H4K12la via HDAC3, promoting SASP expression and offering a new therapeutic direction for VSMC senescence and atherosclerosis. [ABSTRACT FROM AUTHOR]

Persistent inflammation is a major contributor in the development of various inflammatory diseases like atherosclerosis. Our study investigates how transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, interacts with microRNA-146a (miR-146a), within the context of inflammation and atherosclerosis. Micro-RNAs play a critical role in controlling gene expression, and miR-146a is notable for its anti-inflammatory actions. TRPV4 is activated by diverse soluble and mechanical stimuli, and often associated with inflammatory responses in various diseases. Here, we find that TRPV4 negatively regulates miR-146a expression in macrophages, especially following stimulation by lipopolysaccharides or alterations in matrix stiffness. We show that in atherosclerosis, a condition characterized by matrix stiffening, TRPV4 decreases miR-146a expression in aortic tissue macrophages. We find that TRPV4's impacton miR-146a is independent of activation of NFkB, Stat1, P38, and AKT, but is rather mediated through a mechanism involving histone deacetylation instead of DNA methylation at the miR-146a promoter site. Furthermore, we show that N-terminal residues 1 to 130 in TRPV4 is essential in suppression of miR-146a expression in LPS-stimulated macrophages. Altogether, this study identifies a regulatory mechanism of miR-146a expression by TRPV4 which may open new potential therapeutic strategies for managing inflammatory diseases. [ABSTRACT FROM AUTHOR]

Objective: Asthma is linked to atherosclerosis, yet the underlying mediators remain elusive. Eosinophils may contribute to both asthmatic and atherosclerotic inflammation. Hence, this study aimed to explore the potential associations of eosinophils with artery changes among patients with asthma. Methods: We assessed strain values of the common carotid arteries (CCAs) via vascular speckle tracking and compared asthma patients with low (< 300/µl) and high (≥ 300/µl) blood eosinophil counts (BEC). Results: We enrolled 100 patients, 42 with a BEC of < 300 and 58 with a BEC of ≥ 300 n/µl. Patients with high BEC exhibited more severe disease, characterized, e.g., by a higher frequency of acute exacerbations (1.3 ± 2.1 vs. 2.6 ± 2.4 n/year, p = 0.005). Both groups presented similar profiles in terms of conventional cardiovascular risk. The high BEC group demonstrated elevated arterial stiffness, reflected by reduced radial strain (mean radial strain of the right CCA: 2.7 ± 1.4% for BEC ≥ 300 n/µl vs. 3.5 ± 1.7% for BEC < 300 n/µl, p = 0.008; left CCA: 2.6 ± 1.4% vs. 4.1 ± 2.2%, p < 0.001). A weak yet statistically significant negative correlation was observed between BEC and radial strain for the right CCA (R2 = 0.131, b=-0.001, p = 0.001) and left CCA (R2 = 0.086, b=-0.001, p = 0.015). However, the prevalence of cerebrovascular disease was similar in both groups (31,0% vs. 50,0%, p = 0.057). Conclusion: We identified a correlation between BEC and vascular stiffness, which supports the hypothesis that eosinophils may promote atherosclerosis. Clinical trial number: Due to the exploratory and predominantly retrospective nature of the study, trial registration was not conducted. The only prospective procedure conducted was the angiological sonography to evaluate the current state. No ensuing health-related interventions were performed specifically for this study. [ABSTRACT FROM AUTHOR]

Curcumin is a natural polyphenol, with a different name diferuloylmethane, found in Curcuma longa (turmeric) with remarkable antioxidant, antimicrobial, anti-inflammatory, antiangiogenic, and antiplatelet aggregation properties. In recent years, several studies have verified that curcumin may benefit glucolipid metabolic disorders due to its various properties. Glucolipid metabolic disorders, major health threats to human life, is a series of diseases with the metabolic disturbance of glucose and lipid which are influenced by genetic, environmental, psychiatric, dietary, and other factors, including diabetes, hyperlipidemia, hypertension, obesity, metabolic dysfunction-associated fatty liver disease, and atherosclerosis. Here, we discusses the effects and underlying mechanisms on how curcumin alleviate the glucolipid metabolic disorders. [ABSTRACT FROM AUTHOR]

Atherosclerosis remains a major contributor to cardiovascular disease, the leading cause of global morbidity and mortality. Despite the elucidation of several molecular, biochemical, and cellular aspects that contribute to the etio‐pathogenesis of atherosclerosis, much remains to be understood about the onset and progression of this disease. Emerging evidence supports a role for exosomes in the cellular basis of atherosclerosis. Indeed, exosomes of activated monocytes seem to accentuate a positive feedback loop that promotes recruitment of pro‐inflammatory leukocytes. Moreover, in addition to their role in promoting proliferation and invasion of vascular smooth muscle cells, exosomes can also induce neovascularization within lesions and increase endothelial permeability, two important features of fibrous plaques. Depending on their sources and cargo, exosomes can also induce clot formation and contribute to other hallmarks of atherosclerosis. Taken together, it is becoming increasingly evident that a better understanding of exosome biology is integral to elucidating the pathogenesis of atherosclerosis, and may thus provide insight into a potentially new therapeutic target for this disease. [ABSTRACT FROM AUTHOR]

Background Results Conclusion Maintaining low concentrations of plasma low‐density lipoprotein cholesterol (LDLc) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and delays the age at which mature atherosclerotic plaques develop. This substantially reduces the lifetime risk of atherosclerotic cardiovascular disease (ASCVD) events. In this context, plaque development and vulnerability result not only from lipid accumulation but also from inflammation.Changes in the composition of immune cells, including macrophages, dendritic cells, T cells, B cells, mast cells and neutrophils, along with altered cytokine and chemokine release, disrupt the equilibrium between inflammation and anti‐inflammatory mechanisms at plaque sites. Considering that it is not a competition between LDLc and inflammation, but instead that they are partners in crime, the present narrative review aims to give an overview of the main inflammatory molecular pathways linked to raised LDLc concentrations and to describe the impact of lipid‐lowering approaches on the inflammatory and lipid burden. Although remarkable changes in LDLc are driven by the most recent lipid lowering combinations, the relative reduction in plasma C‐reactive protein appears to be independent of the magnitude of LDLc lowering.Identifying clinical biomarkers of inflammation (e.g. interleukin‐6) and possible targets for therapy holds promise for monitoring and reducing the ASCVD burden in suitable patients. [ABSTRACT FROM AUTHOR]

Background: Acute coronary syndrome continues to be a significant cardiovascular issue. Statins are commonly acknowledged as medications that reduce LDL-C levels and stabilize plaques. Nevertheless, their efficacy is limited. Presently, PCSK9 inhibitors are suggested to be advantageous in patients who are already receiving statin treatment. The study seeks to assess the safety and effectiveness of PCSK9 inhibitors in individuals who have been treated with statins after experiencing acute coronary syndrome (ACS), as well as investigate the impact on the characteristics of coronary plaque. Methods: Articles were identified from PubMed, Cochrane Central Register of Controlled Trials, and ProQuest. Our analysis comprised trials and observational studies that compared the plaque phenotype, lipid profile, and safety outcomes between PCSK9 inhibitors and a control group in patients with acute coronary syndrome who were already being treated with statins. The random-effect model was used to measure the pooled effect, which was presented in terms of mean difference, standardized mean difference, and risk ratio. Results: Acquired 12 studies that fulfilled our criteria. The addition of PCSK9 inhibitors ameliorates the plaque phenotype significantly in terms of percent atheroma volume (P = 0.02), total atheroma volume (P < 0.010), fibrous cap thickness (P < 0.00001), lipid arc (P < 0.00001), quantitative flow ratio (P = 0.003), and diameter of stenosis (P = 0.0003) but not in lipid/lesion length (P = 0.17). The administration of PCSK9 inhibitors led to a considerable improvement in all lipid profiles (P < 0.00001). Regarding safety analysis, there is no substantial disparity in the likelihood of non-serious side events (RR 1.21; P = 0.2), however, a significant reduction in the risk of serious adverse effects (RR 0.77; P = 0.04) in the PCSK9 inhibitor group. Conclusions: The addition of PCSK9 inhibitors compared to statin-only treatment led to a majority of patients experiencing significant benefits in terms of safety and efficacy following ACS. [ABSTRACT FROM AUTHOR]

The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention. [ABSTRACT FROM AUTHOR]

This work is an analytical review dedicated to the search for driver mechanisms of epigenetic changes in atherosclerosis pathogenesis. The disease affects the cardiovascular system in the adult population, mainly the elderly and senile. Atherosclerosis is accompanied by progressive deposition of cholesterol and lipoproteins in vessels intima with inflammation, narrowing of the lumen, and impaired blood supply to tissues and organs. These processes are characterized by changes in the expression of the CACNA1C, GABBR2, TCF7L2, DCK, NRP1, PBX1, FANCC, CCDC88C, TCF12, and ABLIM1 genes. Prevention of atherosclerosis is physical activity, the mechanisms of which are not fully understood. Experimental models have shown that regular training not only has a protective effect on the development of atherosclerosis but also inhibits the progression of an already developed disease with a decrease in vascular stenosis and an increase in the concentration of collagen and elastin and matrix metalloproteinases in plaques. These results have been confirmed by clinical studies. The purpose of this review was to systematize the accumulated results on the causes of epigenetic changes, including those under the influence of regular training, causing changes in the expression of specific microRNAs in atherosclerosis. It was found that physical exercise in Apo–/– mice increases the expression of miR-126 and miR-146a (inhibiting the TLR4 and TRAF genes), miR-20a (affecting PTEN), and miR-492 (suppressing RETN gene mRNA). Clinical studies have shown an increase in the levels of miR-146a, miR-126, miR-142-5p, and miR-424-5p and a decrease in the transcription of miR-15a-5p, miR-93-5p, and miR-451 under the influence of aerobic training. It has been suggested that the drivers of epigenetic changes in atherosclerosis are transposons pathologically activated during aging, the transcription of which can change under the influence of physical training, which is accompanied by impaired expression of long noncoding RNAs and microRNAs derived from transposons. Analysis of the published data allowed us to identify 36 such microRNAs, 25 of which showed identical changes in levels during aging and atherosclerosis. [ABSTRACT FROM AUTHOR]

Atherosclerosis, as the main root cause, makes cardiovascular diseases (CVDs) a substantial worldwide health concern. Inflammation and disrupted cholesterol metabolism are the primary clinical risk elements contributing to the onset of atherosclerosis. Few works exist on the improvement effect of gut microbiota on atherosclerosis. One specific probiotic strain, Enterococcus faecium NCIMB11508, has shown promise in mitigating inflammation. Consequently, it is critical to investigate its potential in reducing the progression of atherosclerosis. In our study, we administered E. faecium NCIMB11508 orally to ApoE−/− mice, resulting in a decrease in the formation of atherosclerotic lesions. Additionally, it demonstrated the ability to lower the inflammatory factor levels both in the aorta and blood serum while maintaining the integrity of the small intestine against lipopolysaccharides. Moreover, E. faecium NCIMB11508 had a beneficial impact on the gut microbiota composition by increasing the levels of short-chain fatty acids (SCFAs), which in turn helped to reduce inflammation and protect the intestine. The probiotic E. faecium NCIMB11508, according to our research, has a definitive capacity to prevent atherosclerosis progression by beneficially altering the SCFA composition in the gut microbiota of ApoE−/− mice. [ABSTRACT FROM AUTHOR]

Introduction: Atherosclerosis is a leading cause of cardiovascular disease, characterized by lipid accumulation and chronic inflammation within arterial walls. Early detection in young adults is crucial for preventing adverse cardiovascular events. This study investigates the associations between inflammatory indices, lipid biomarkers, and the presence of atherosclerosis in patients aged 18 to 55 years. Methods: A cross-sectional study was conducted involving 89 participants divided into two groups: 62 patients with documented atherosclerosis (main group) and 27 healthy controls without significant atherosclerosis. Comprehensive data—including demographic information, medication use, imaging results, laboratory parameters, and calculated inflammatory indices (SIRI, SII, AISI, NLR, PLR, MLR)—were collected. Statistical analyses included correlation assessments, group comparisons using the Mann–Whitney U test, logistic regression modeling, feature importance analysis with Random Forest and Gradient Boosting classifiers, receiver operating characteristic (ROC) curves, and K-means clustering. Results: Significant differences were observed between the main and control groups. Patients with atherosclerosis exhibited elevated inflammatory indices (SIRI, NLR, MLR, SII) and lipid profile abnormalities (higher TC and LDL-C, lower HDL-C). Lp(a) and ANGPTL3 levels were significantly higher in the main group (p < 0.001 and p < 0.01, respectively). Logistic regression identified SIRI and ANGPTL3 as significant predictors of atherosclerosis, with the model demonstrating high accuracy (77%) and sensitivity (93%). Feature importance analysis confirmed the significance of SIRI and ANGPTL3, alongside traditional lipid biomarkers, in predicting disease presence. ROC analysis showed excellent model performance (AUC > 0.80). Clustering analysis revealed two distinct patient subgroups characterized by predominant inflammatory profiles or lipid metabolism disturbances. Conclusions: Systemic inflammation and lipid abnormalities play significant roles in early atherosclerosis among young adults. Elevated SIRI and ANGPTL3 levels are potent predictors of disease presence. The integration of inflammatory indices and lipid biomarkers into predictive models enhances risk stratification and supports personalized medicine approaches. [ABSTRACT FROM AUTHOR]

Background/Objectives: The identification of coronary artery disease (CAD) high-risk individuals is a major clinical need for timely diagnosis and intervention. Many different polygenic scores (PGSs) for CAD risk are available today to estimate the genetic risk. It is necessary to carefully choose the score to use, in particular for studies on populations, which are not adequately represented in the large datasets of European biobanks, such as the Italian one. This work aimed to analyze which PGS had the best performance within the Italian population. Methods: We used two Italian independent cohorts: the EPICOR case–control study (576 individuals) and the Atherosclerosis, Thrombosis, and Vascular Biology (ATVB) Italian study (3359 individuals). We evaluated 266 PGS for cardiovascular disease risk from the PGS Catalog, selecting 51 for CAD. Results: Distributions between patients and controls were significantly different for 49 scores (p-value < 0.01). Only five PGS have been trained and tested for the European population specifically. PGS003727 demonstrated to be the most accurate when evaluated independently (EPICOR AUC = 0.68; ATVB AUC = 0.80). Taking into account the conventional CAD risk factors further enhanced the performance of the model, particularly in the ATVB study (p-value = 0.0003). Conclusions: European CAD PGS could have different risk estimates in peculiar populations, such as the Italian one, as well as in various geographical macro areas. Therefore, further evaluation is recommended for clinical applicability. [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]

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily recognized for its role in lipid metabolism, but recent evidence suggests that it may have broader implications due to its diverse tissue expression. Objective: This review aims to explore the multifaceted functions of PCSK9, highlighting its pro‐atherosclerotic effects, including its impact on circulating lipoprotein variables, non‐low‐density lipoprotein receptors, and various cell types involved in atherosclerotic plaque development. Conclusions: PCSK9 exhibits diverse roles beyond lipid metabolism, potentially contributing to atherosclerosis through multiple pathways. Understanding these mechanisms could offer new insights into therapeutic strategies targeting PCSK9 for cardiovascular disease management. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is an important pathological feature of cardiovascular diseases such as myocardial infarction, stroke and other highly fatal diseases. Phlegm and dampness are considered to be an important pathogenesis of AS, which is difficult to heal and can cause complications. The establishment of an animal model with AS and phlegm-dampness syndrome, which could reflect the features of traditional Chinese medicine (TCM), and objective evaluation system are an important element of modern integrated TCM and western medicine research on cardiovascular diseases. It is of great significance for TCM to prevent and treat cardiovascular diseases. This article summarizes the scientific connotations of traditional Chinese and western medicine for AS and phlegm-dampness syndrome, comprehensively summarizes the current status of construction and evaluation in experimental animal model, analyzes the problems of current model, and discusses the factors of model construction and evaluation. Our aim is to establish normalized and standardized animal model with AS of phlegm-dampness syndrome. [ABSTRACT FROM AUTHOR]

For symptomatic stenosis in the middle cerebral artery (MCA), intracranial angioplasty and stenting are frequently employed. However, limited data exist regarding their long-term impact. Our study demonstrates the long-term advantages in preventing ischemic events through a 5-year follow-up period. A set of 41 individuals with symptomatic stenosis in the MCA who underwent angioplasty or stenting procedures between October 2004 and April 2018 at various hospitals in Southwest China were prospectively enrolled in the study. The rates of successful revascularization, complications, imaging observations, and clinical outcomes were systematically assessed. A total of 41 individuals successfully underwent stenting, respectively. After stenting, the extent of stenosis was decreased from 71.8% (56–87.8%) to 24.9% (0–45%). The mean follow-up period is 36.9 ± 13.68 months (range, 11–67 months). There was no deterioration of neurological function or a new ischemic event. A DSA or CT angiography was conducted after the procedure and demonstrated no in-stent restenosis. No patient experienced restenosis below 50% during the mean follow-up period. The morbidity and mortality rates of the case series were 7.3% and 2.4%, respectively. In the treatment of symptomatic MCA atherosclerotic stenoses, intracranial angioplasty and stenting are demonstrated to be technically feasible and safe. Its early and long-term efficacy on ischemic event prevention is acceptable, with a reduced level of restenosis, although the representative sample is tiny. [ABSTRACT FROM AUTHOR]

Background: Coronary artery calcium score (CACS) and carotid intima-media thickness (CIMT) are important markers for early detection of coronary atherosclerosis. The study aimed to investigate the relationship between the CIMT and the CACS as markers for atherosclerotic coronary artery disease (CAD). Methods: This single-center prospective study enrolled 41 cases with suspected CAD. The cases underwent carotid artery US and CA noncontrast CT (NCCT). A radiologist with eight years of experience in vascular US imaging performed the carotid artery US, while two radiologists with ten years of experience in cardiac imaging analyzed the coronary artery CT images and assigned a CAC-DRS category for each case. We used the Pearson correlation test to calculate the correlation between CIMT and CACS. The receiver operating characteristics (ROC) curve was used to estimate the best cutoff value of CIMT in predicting CA heavy calcification. Results: The study included 41 cases of suspected CAD, of which 12-showed heavy, and 29 showed non-heavy CA calcification. The mean CACS was 163, and the highest CIMT was 0.785 mm among the included patients. There was a significant positive correlation between the CACS and the highest CIMT (r 0.606 and P <0.001). A CIMT > 0.8 mm was the best cutoff for predicting heavy calcification, with a sensitivity of 91.7%, a specificity of 65.5%, and an accuracy of 73.2% based on ROC curve analysis. Conclusions: CIMT and CACS can be considered non-invasive predictive measures for CA atherosclerosis and subsequent CAD. Moreover, these markers might help cardiologists in clinical management. [ABSTRACT FROM AUTHOR]

Background and aims: We previously reported that Oxy210, an oxysterol-based drug candidate, exhibits antifibrotic and anti-inflammatory properties. We also showed that, in mice, it ameliorates hepatic hallmarks of non-alcoholic steatohepatitis (NASH), including inflammation and fibrosis, and reduces adipose tissue inflammation. Here, we aim to investigate the effects of Oxy210 on atherosclerosis, an inflammatory disease of the large arteries that is linked to NASH in epidemiologic studies, shares many of the same risk factors, and is the major cause of mortality in people with NASH. Methods: Oxy210 was studied in vivo in APOE*3-Leiden.CETP mice, a humanized mouse model for both NASH and atherosclerosis, in which symptoms are induced by consumption of a high fat, high cholesterol "Western" diet (WD). Oxy210 was also studied in vitro using two cell types that are important in atherogenesis: human aortic endothelial cells (HAECs) and macrophages treated with atherogenic and inflammatory agents. Results: Oxy210 reduced atherosclerotic lesion formation by more than 50% in hyperlipidemic mice fed the WD for 16 weeks. This was accompanied by reduced plasma cholesterol levels and reduced macrophages in lesions. In HAECs and macrophages, Oxy210 reduced the expression of key inflammatory markers associated with atherosclerosis, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand 2 (CCL2), vascular cell adhesion molecule-1 (VCAM-1), and E-Selectin. In addition, cholesterol efflux was significantly enhanced in macrophages treated with Oxy210. Conclusions: These findings suggest that Oxy210 could be a drug candidate for targeting both NASH and atherosclerosis, as well as chronic inflammation associated with the manifestations of metabolic syndrome. [ABSTRACT FROM AUTHOR]

The inhibitor-kappaB kinase epsilon (IKKε) represents a non-canonical IκB kinase that modulates NF-κB activity and interferon I responses. Inhibition of this pathway has been linked with atherosclerosis and metabolic dysfunction-associated steatotic liver disease (MASLD), yet the results are contradictory. In this study, we employed a combined model of hepatic PCSK9D377Y overexpression and a high-fat diet for 16 weeks to induce atherosclerosis and liver steatosis. The development of atherosclerotic plaques, serum lipid concentrations, and lipid metabolism in the liver and adipose tissue were compared between wild-type and IKKε knock-out mice. The formation and progression of plaques were markedly reduced in IKKε knockout mice, accompanied by reduced serum cholesterol levels, fat deposition, and macrophage infiltration within the plaque. Additionally, the development of a fatty liver was diminished in these mice, which may be attributed to decreased levels of multiple lipid species, particularly monounsaturated fatty acids, triglycerides, and ceramides in the serum. The modulation of several proteins within the liver and adipose tissue suggests that de novo lipogenesis and the inflammatory response are suppressed as a consequence of IKKε inhibition. In conclusion, our data suggest that the knockout of IKKε is involved in mechanisms of both atherosclerosis and MASLD. Inhibition of this pathway may therefore represent a novel approach to the treatment of cardiovascular and metabolic diseases. [ABSTRACT FROM AUTHOR]

The triad formed by thyroid dysfunction, metabolic syndrome (MetS), and cardiovascular (CV) risk forms a network with many connections that aggravates health outcomes. Thyroid hormones (THs) play an important role in glucose and lipid metabolism and hemodynamic regulation at the molecular level. It is noteworthy that a bidirectional association between THs and MetS and their components likely exists as MetS leads to thyroid dysfunction, whereas thyroid alterations may cause a higher incidence of MetS. Thyroid dysfunction increases insulin resistance, the circulating levels of lipids, in particular LDL-C, VLDL-C, and triglycerides, and induces endothelial dysfunction. Furthermore, THs are important regulators of both white and brown adipose tissue. Moreover, the pathophysiological relationship between MetS and TH dysfunction is made even tighter considering that these conditions are usually associated with inflammatory activation and increased oxidative stress. Therefore, the role of THs takes place starting from the molecular level, then manifesting itself at the clinical level, through an increased risk of CV events in the general population as well as in patients with heart failure or acute myocardial infarction. Thus, MetS is frequently associated with thyroid dysfunction, which supports the need to assess thyroid function in this group, and when clinically indicated, to correct it to maintain euthyroidism. However, there are still several critical points to be further investigated both at the molecular and clinical level, in particular considering the need to treat subclinical dysthyroidism in MetS patients. [ABSTRACT FROM AUTHOR]

Patients with unstable angina present clinical characteristics of atherosclerotic plaque vulnerability, contrary to chronic coronary syndrome patients. The process of athersclerotic plaque destabilization is also regulated by microRNA particles. In this study, the investigation on expression levels of microRNAs inhibiting the expression of proteins that protect from atherosclerotic plaque progression (miR-92a inhibiting KLF2, miR-10b inhibiting KLF4, miR-126 inhibiting MerTK, miR-98 inhibiting IL-10, miR-29b inhibiting TGFβ1) was undertaken. A number of 62 individuals were enrolled—unstable angina (UA, n = 14), chronic coronary syndrome (CCS, n = 38), and healthy volunteers (HV, n = 10). Plasma samples were taken, and microRNAs expression levels were assessed by qRT-PCR. As a result, the UA patients presented significantly increased miR-10b levels compared to CCS patients (0.097 vs. 0.058, p = 0.033). Moreover, in additional analysis when UA patients were grouped together with stable patients with significant plaque in left main or proximal left anterior descending ("UA and LM/proxLAD" group, n = 29 patients) and compared to CCS patients with atherosclerotic lesions in other regions of coronary circulation ("CCS other" group, n = 25 patients) the expression levels of both miR-10b (0.104 vs. 0.046; p = 0.0032) and miR-92a (92.64 vs. 54.74; p = 0.0129) were significantly elevated. In conclusion, the study revealed significantly increased expression levels of miR-10b and miR-92a, a regulator of endothelial protective KLF factors (KLF4 and KLF2, respectively) in patients with more vulnerable plaque phenotypes. [ABSTRACT FROM AUTHOR]

Atherosclerosis, a term derived from the Greek "athero" (atheroma) and "sclerosis" (hardening), is a long-standing process that leads to the formation of atheromatous plaques in the arterial wall, contributing to the development of atherosclerotic cardiovascular disease. The proliferation and migration of vascular smooth muscle cells (VSMCs) and the switching of their phenotype play a crucial role in the whole process. Retinoic acid (RA), a natural derivative of vitamin A, has been used in the treatment of various inflammatory diseases and cell proliferation disorders. Numerous studies have demonstrated that RA has an important inhibitory effect on the proliferation, migration, and dedifferentiation of vascular smooth muscle cells, leading to a significant reduction in atherosclerotic lesions. In this review article, we explore the effects of RA on the pathogenesis of atherosclerosis, focusing on its regulatory action in VSMCs and its role in the phenotypic switching, proliferation, and migration of VSMCs. Despite the potential impact that RA may have on the process of atherosclerosis, further studies are required to examine its safety and efficacy in clinical practice. [ABSTRACT FROM AUTHOR]

Background: To date, PCSK9 inhibitors are well known for eliminating cardiac and cerebral artery ischemia events by lowering the serum lipid level. However, the pathophysiological value of in-plaque PCSK9 expression is still unclear. Methods: Advanced plaques removed by carotid endarterectomy were sectioned and stained to identify the PCSK9 expression pattern and its co-expression with rupture-relevant markers. To investigate the correlation of PCSK9 expression with regional blood shear flow, hemodynamic characteristics were analyzed using computational fluid dynamics, and representative parameters were compared between PCSK9 positive and negative staining plaques. To explore this phenomenon in vitro, human aortic vascular smooth muscle cells were used to overexpress and knock down PCSK9. The impacts of PCSK9 modulations on mechanical sensor activity were testified by western blot and immunofluorescence. Real-time polymerase chain reaction was used to evaluate the transcription levels of downstream rupture-prone effectors. Results: PCSK9 distribution in plaque preferred cap and shoulder regions, residing predominantly in smooth muscle actin-positive cells. Cap PCSK9 expression correlated with fibrous cap thickness negatively and co-expressed with MMP-9, both pointing to the direction of plaque rupture. A hemodynamic profile indicated a rupture-prone feature of cap PCSK9 expression. In vitro, overexpression and knockdown of PCSK9 in human aortic vascular smooth muscle cells has positive modulation on mechanical sensor Yes-associated protein 1 (YAP) activity and transcription levels of its downstream rupture-prone effectors. Serial section staining verified in situ colocalization among PCSK9, YAP, and downstream effectors. Conclusions: Cap PCSK9 possesses a biomarker for rupture risk, and its modulation may lead to a novel biomechanical angle for plaque interventions. [ABSTRACT FROM AUTHOR]

Atherosclerosis is commonly known as an inflammatory disease that is characterized by lipid deposition in the arterial wall, causing gradual restriction or complete blockade of blood flow, which can cause complications such as myocardial infarction, stroke, or peripheral artery disease. Several factors contribute to initiation and progression of atherosclerotic plaque formation. The role of macrophages and leukocytes in atherosclerosis has been well explored. Here, we provide an overview of what has been reported on the role and impact of the arterial cells on plaque formation, and vice versa. The atherogenic environment can trigger transformation and dedifferentiation of the endothelial cells (ECs), smooth muscle cells, and fibroblasts (FBs) whereby they can either directly contribute to plaque formation or influence its composition. Recent studies have demonstrated the plasticity in the identity of the arterial cells, the formation of intermediate cell types that share the characteristics of multiple cell types, and have revealed novel roles and functions for these cells in atherosclerosis. The potential for all vascular cells to cross-transdifferentiate, and detection of cells with mosaic characteristics in the atherosclerotic plaques reveal that the plaque environment is a complex and dynamic environment that could regulate the disease progression independent from the circulating lipid levels. We will also provide an overview on the interplay between sex and atherosclerosis, which has remained an underexplored area. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to perform specific causal validation of nursing diagnosis Risk for thrombosis (00291) of the NANDA International (NANDA‐I) classification. Methods: This is a case–control study conducted in a university hospital from January to October 2020. A total of 516 adult patients were included—344 in the Case Group (with venous or arterial thrombosis evidenced by imaging) and 172 in the Control Group (without thrombosis). Statistical analysis was performed by univariate and multivariate logistic regression test, and odds ratios were calculated to measure the effect of exposure between groups. The study was approved by the Research Ethics Committee. Findings: The patients were predominantly female and aged 59 ± 16 years. In the univariate logistic analysis, five risk factors were significantly associated with thrombosis, two at‐risk populations and 12 associated conditions. In the multivariate regression model, the following risk factors remained independently associated (p < 0.05): inadequate knowledge of modifiable factors (OR: 3.03; 95% CI: 1.25–8.56) and ineffective medication self‐management (OR: 3.2; 95% CI:1.77–6.26); at‐risk populations with history (OR: 2.16; 95% CI: 1.29–3.66) and family history of thrombosis (OR:2.60; 95% CI: 1.03–7.49); and the conditions associated with vascular diseases (OR:6.12; 95% CI:1.69–39.42), blood coagulation disorders (OR: 5.14; 95% CI:1.85–18.37), atherosclerosis (OR:2.07; 95% CI: 1.32–3.27), critical illness (OR: 2.28; 95% CI: 1.42–3.70), and immobility (OR: 2.09; 95% CI: 1.10–4.12). Conclusions: The clinical validation allowed to establish strong evidence for the refinement of the diagnosis Risk for thrombosis and, consequently, to raise its level of evidence in the classification of NANDA‐I. Implications for nursing practice: The evidence pointed out by this study favors the establishment of thrombosis diagnosis in an accurate way by nurses in clinical practice, directing preventive interventions to patients in this risk condition. [ABSTRACT FROM AUTHOR]

Lipoprotein (a), also known as Lp(a), is a type of lipoprotein that is structurally similar to low-density lipoprotein (LDL). It consists of an LDL-like particle with a specific protein called apolipoprotein (a) attached to it. Elevated levels of Lp(a) in the blood are significantly involved in the development of cardiovascular diseases, particularly atherosclerosis and aortic stenosis, by contributing to inflammation, oxidative stress, and calcification. Numerous epidemiological studies confirm the strong association between high Lp(a) levels and an increased risk of cardiovascular events such as myocardial infarction and stroke, highlighting the importance of including Lp(a) screening in comprehensive cardiovascular health evaluations. The positive correlation between high Lp(a) levels and increased cardiovascular risk underscores the need for developing appropriate and effective treatments to lower Lp(a) levels in patients. [ABSTRACT FROM AUTHOR]

Puerarin (Pue) has significant antioxidant and anti‐inflammatory properties. This work was designed to clarify and investigate the potential mechanisms of Pue in atherosclerosis (AS) progression. In vivo, acrolein (Acr) was inhaled through drinking water to construct AS model. In vitro, CCK‐8 assay and lactate dehydrogenase (LDH) assay kit were used to detect cell viability. Apoptosis was detected by flow cytometry. The content of malondialdehyde (MDA) was determined by commercial kit, the level of inflammatory factors was detected by ELISA, and proteins were determined by western blot. Pue administration could effectively reduce blood lipid level in Acr‐fed mice. Pue suppressed oxidative stress, the formation of atherosclerotic plaques, and the process of aortic histological changes. Pue pretreatment decreased MDA in HUVECs and maintained the activity of antioxidant enzymes. Pue upregulated SIRT1/Nrf2 cascade in HUVECs. Pue increased MYH9 and inhibited NLRP3 inflammasome‐related proteins, and the inhibition of MYH9 significantly impaired Pue‐induced Nrf2 activation. Moreover, HUVEC cytotoxicity and apoptosis are alleviated by Pue, in addition to NLRP3‐mediated pyroptosis in HUVECs induced by Acr. MYH9 inhibitors effectively suppressed the pyroptosis induced by Acr and prevented injury to HUVECs. In addition, Pue promoted SIRT1/Nrf2 cascade activation in HUVECs. Pue may alleviate Acr‐induced AS by activating the MYH9‐mediated SIRT1/Nrf2 cascade to inhibit inflammasome activation. [ABSTRACT FROM AUTHOR]

Free fatty acids (FFAs) have emerged as significant risk factors for atherosclerosis (AS). Prolonged exposure to FFAs induces vascular endothelial injury, including inflammatory responses and oxidative stress, which are central events in AS. Chromofungin (CHR), a peptide derived from chromogranin A (CGA), has been implicated in various biological functions. However, its physiological roles in endothelial biology and its involvement in the pathological development of AS have not been previously reported. In the present study, we investigated the underlying mechanisms through which CHR exerts its beneficial effects on FFA‐challenged human aortic endothelial cells (HAECs). We found that treatment with CHR ameliorated the FFA‐induced reduction in cell viability and increase in lactate dehydrogenase (LDH) release. Additionally, CHR mitigated oxidative stress by reducing mitochondrial reactive oxygen species (ROS) levels and increasing superoxide dismutase (SOD) activity. Furthermore, exposure to FFAs increased NADPH oxidase (NOX) 4 expression at both the mRNA and protein levels, which were attenuated by CHR in a dose‐dependent manner. Notably, CHR reduced the levels of nucleotide‐binding domain and leucine‐rich repeat‐containing (NLR) family pyrin domain containing 3 (NLRP3), apoptosis‐associated speck‐like protein containing a CARD (ASC), and cleaved caspase‐1 (p10), key components of the NLRP3 inflammasome complex, as well as interleukin 1β (IL‐1β) and interleukin‐18 (IL‐18) expression. Mechanistically, it was demonstrated that FFAs reduced the phosphorylation of AMP‐activated protein kinase (AMPK) and acetyl‐CoA carboxylase (ACC), which were rescued by CHR in a dose‐dependent manner. Conversely, inhibition of AMPK with its specific inhibitor compound C abolished the protective effects of CHR against FFA‐induced activation of the NLRP3 inflammasome in HAECs. Based on these findings, we conclude that CHR may serve as a promising agent for maintaining normal endothelial cell function and treating AS. [ABSTRACT FROM AUTHOR]