Cardiac fibrosis following myocardial infarction (MI) is a critical determinant of progressive cardiac dysfunction, yet the underlying mechanisms driving this pathological process remain incompletely understood. Elucidating these regulatory pathways holds profound implications for improving post-MI prognosis. Our prior work demonstrated that chronic intermittent hypoxia (CIH) exacerbates cardiac fibrosis while modulating the expression of long non-coding RNA (lncRNA) nonnmmut065573 (tentatively designated LncRNA-IH) in cardiac tissues. Herein, we sought to determine the role of LncRNA-IH in post-MI cardiac fibrosis and its underlying mechanisms. Using a C57BL/6 mouse model of MI, we established a mouse model with cardiac-specific overexpression of LncRNA-IH to evaluate post-MI cardiac fibrosis. In vitro, primary cardiac fibroblasts (MCF) and the PA12 cell line were subjected to LncRNA-IH overexpression or siRNA-mediated knockdown, and cell proliferation and migration were assessed. Transcriptomic profiling was performed to characterize LncRNA-IH-induced changes in cardiac gene expression and signaling pathways, aiming to elucidate the molecular mechanisms involved. Results showed that CIH significantly exacerbated post-MI cardiac fibrosis, and LncRNA-IH was predominantly localized to cardiac fibroblasts. Cardiac-specific overexpression of LncRNA-IH in MI mice markedly exacerbated post-MI cardiac dysfunction and fibrosis. In vitro, LncRNA-IH overexpression significantly enhanced the proliferation and migration capacities of primary cardiac fibroblasts and PA12 cells, whereas these effects were abrogated by LncRNA-IH knockdown. Transcriptomic analysis revealed that LncRNA-IH elicited significant alterations in cardiac gene expression profiles, specifically activating the TGF-β1 signaling pathway and upregulating the expression of its downstream target, ZEB1. Collectively, our findings indicate that LncRNA-IH promotes cardiac fibroblast proliferation and migration, thereby exacerbating post-MI cardiac remodeling, at least in part through activation of the TGF-β1 signaling pathway. This study identifies LncRNA-IH as a potential therapeutic target for mitigating post-MI cardiac fibrosis and preserving cardiac function.

BackgroundDyslipidemia remains a major modifiable contributor to China's cardiovascular disease (CVD) burden, yet large-scale evidence on risk-stratified management gaps is lacking.MethodsIn this nationwide study across 1,785 hospitals in 28 Chinese provinces, 604,250 outpatients with dyslipidemia were enrolled. We analyzed lipid levels, quantified control rate among treated population and rates of requiring lipid-lowering therapy (LLT) among untreated population across regions, socioeconomic status, and demographic groups.ResultsTotal cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were higher among females, middle-aged individuals, and individuals with obesity. LDL-C levels were also higher among urban residents, while TC showed no significant urban-rural difference. Triglyceride (TG) levels were higher in males, middle-aged individuals, individuals with obesity, and rural residents. Among treated population, LDL-C/non-HDL-C control rates reached 95% in low-risk, 70-90% in moderate-risk, 40-50% in high-risk, and 5-15% in very-high-risk groups. Among untreated population, rates of requiring LLT reached about 20% in the low-risk group and over 70% in moderate- and high-risk groups. After adjusting for covariates, males, older individuals, smokers, patients with hypertension or type 2 diabetes mellitus, as well as those in rural and low-gross-domestic-product areas were associated with lower lipid control rates and higher treatment needs.ConclusionsOur findings highlight the urgent need for risk-stratified lipid management in primary care, improved access to LLT, and policies addressing regional and socioeconomic disparities to enhance lipid control and reduce CVD burden in China. Lessons from China can inform global strategies to improve lipid management and reduce the CVD burden.

ObjectiveThis study aimed to develop a novel risk prediction model for coronary heart disease (CHD) based on lipid subfraction and lipidomics data.MethodsLipid subfraction analysis was conducted on 624 subjects (312 CHD, 312 controls) using Vertical Auto Profile (VAP). The participants were randomly divided into a training cohort (n = 422, 211 CHD, 211 controls) and a validation cohort (n = 202, 101 CHD, 101 controls) at a 2:1 ratio, stratified by CHD status. Untargeted lipidomics was performed on 16 subjects (8 CHD, 8 controls) randomly selected from the total enrolled population using UHPLC-Q-TOF/MS. Lasso regression with ten-fold cross-validation was applied to screen key predictive factors, followed by multivariate logistic regression to construct a risk prediction model. The false discovery rate (FDR) was controlled using the Benjamini–Hochberg procedure for multiple comparisons. Model discriminative performance was evaluated using ROC curve analysis.ResultsA total of 2,335 lipid molecules across eight classes were identified. After FDR correction, the differential lipids remained statistically significant. CHD patients exhibited significant upregulation of RLP-C and sdLDL-C-related lipid components, while HDL2B-related lipids were markedly downregulated. KEGG pathway enrichment analysis revealed that differential lipids were mainly enriched in glycerophospholipid metabolism, choline metabolism in cancer, and fat digestion and absorption. Multivariate logistic regression identified Lp(a) (OR = 1.288), RLP-C (OR = 3.848), sdLDL-C (OR = 5.317), age (OR = 1.053), systolic blood pressure (OR = 1.075), and fasting plasma glucose (OR = 3.903) as independent risk factors for CHD, whereas HDL2B (OR = 1.416 × 10−6) was a protective factor. In the validation cohort, the model achieved an AUC of 0.867 (95% CI: 0.8087–0.9252). Using an optimal cutoff of 0.4726 (Youden index = 0.628), the model demonstrated a sensitivity of 81.4% and a specificity of 81.4%.ConclusionThis study successfully constructed a multivariate logistic regression risk prediction model integrating novel lipid subfractions (sdLDL-C, RLP-C, HDL2B, Lp(a)) and routine clinical variables (age, SBP, FPG). The model exhibits acceptable predictive performance and may provide a complementary tool for CHD risk assessment, pending external validation in larger prospective cohorts.

Background and aims Targeting key enzymes in hepatic de novo lipogenesis (DNL) presents a promising strategy for treating hypercholesterolemia. However, the precise regulatory mechanisms governing hepatic DNL remain incompletely understood. Cytosolic citrate plays a crucial role in DNL, with aconitase 1 (ACO1), a key enzyme in citrate metabolism, potentially influencing lipid metabolism. The aim of this study was to clarify the role of hepatic ACO1 in regulating both hepatic and systemic lipid homeostasis. Methods ACO1 expression and activity were assessed in liver tissues from multiple hypercholesterolemic animal models. Using liver-specific genetic manipulation, we examined the effects of hepatic ACO1 knockout and overexpression on hypercholesterolemia and atherosclerosis. Targeted metabolomics and stable isotope-based flux analysis were used to profile hepatic substrate utilization patterns. Results Hepatic ACO1 expression was significantly reduced in both hypercholesterolemic patients and animal models. Hepatocyte-specific ACO1 deletion exacerbated dyslipidemia, while ACO1 overexpression improved hypercholesterolemia, hepatic steatosis, and atherosclerosis in mouse models. Mechanistically, ACO1 overexpression redirected cytosolic citrate metabolism toward α-ketoglutarate, thereby limiting acetyl-CoA availability for DNL and suppressing fatty acid and cholesterol synthesis. These lipid-lowering effects were dependent on ACO1 enzymatic activity, as catalytically inactive ACO1 mutants failed to replicate the observed benefits. Conclusion Our findings identify hepatic ACO1 as a critical regulator of lipid metabolism homeostasis. Promoting ACO1-mediated citrate redirection effectively mitigates hypercholesterolemia and atherosclerosis by suppressing hepatic DNL, highlighting ACO1 as a potential target for lipid-lowering therapies.

Rationale: Abdominal aortic aneurysm (AAA) is a highly lethal cardiovascular disorder for which there is no effective medication to date. Kinesin family member 13b (KIF13B), a vital motor protein, has been recently identified as a novel regulator of lipid metabolism. However, the role of KIF13B in AAA development has not been documented. Methods: We determined the expression of KIF13B in aortic tissues from clinical patients and porcine pancreatic elastase (PPE) or angiotensin II (ANG II)-induced AAA mouse models. To investigate the influence of KIF13B on AAA expansion, we established global, myeloid cell-specific and vascular smooth muscle cell (VSMC)-specific conditional Kif13b-deficient mice in PPE and/or ANG II-induced AAA models. Results: RNA-seq data from GEO database (GSE57691) revealed a significant decrease in KIF13B gene expression within the aortic tissues of patients with AAA. KIF13B protein levels were largely reduced in aortic tissue samples from patients and two mouse models with AAA. Complete inactivation of Kif13b or depleting Kif13b from myeloid cells but not smooth muscle cells (SMCs) exacerbated AAA development. Mechanistic studies identified transcription factor EB (TFEB) as a critical downstream target of KIF13B. KIF13B stabilized and upregulated TFEB by enhancing its deubiquitination through an interaction with deubiquitinase USP9X to maintain the proper function of lysosomes, thus inhibiting the senescence-associated secretory phenotype (SASP) and proinflammatory response of macrophages. Moreover, restoration of macrophage Kif13b or senolytic therapy dramatically mitigated AAA expansion in vivo. Conclusions: In the present study, we provided a new insight into the pathogenesis of AAA and defined a KIF13B-USP9X-TFEB axis that is essential for the regulation of macrophage function, suggesting that macrophage-derived Kif13b is a beneficial regulator of vascular homeostasis and targeting KIF13B could be a potential therapeutic approach for the treatment of human AAA disease in future clinical trial.

AT hook DNA-binding protein (AHDC1/Gibbin) is a nuclear protein with currently undefined function and structure. De novo nonsense or frameshift mutations in the AHDC1 gene have been identified as the causative factor for Xia-Gibbs syndrome (XGS, OMIM#615829) in 2014, a neurodevelopmental disorder characterized by intellectual disability and developmental delay (1). XGS occurs in infancy and is often accompanied by hypotonia, followed by global developmental and expressive language delays, ultimately leading to intellectual disabilities (2).Whole-exome sequencing has identified more than 390 individuals worldwide with XGS, with the number continually increasing as sequencing diagnostic techniques are widely adopted. The XGS registry was established in 2014, with detailed clinical records contributed by over 100 families who have consented to participate in additional research activities (3), presenting the opportunity to uncover the mutation spectrum and pathogenesis of XGS. Given the clinical importance, urgent investigations are required to explore the functional role of AHDC1/Gibbin and unravel the molecular mechanisms underlying its pathogenic mutations. In this opinion article, we synthesize recent findings on the pathogenic variants of the AHDC1 gene and its protein biological functions, highlighting several critical scientific inquiries that demand immediate attention.XGS primarily arises from spontaneous pathogenic truncating mutations of the AHDC1 gene on chromosome 1 at locus 1p36.11. Notably, only the sixth exon of the AHDC1 gene encodes protein, while the rest are non-coding regions. The coding sequence exhibits remarkable conservation among species at the nucleotide level.Similarly, the 3' non-coding exons maintain a level of conservation akin to that of coding exons, implying their potential importance (1). To date, pathogenic mutations have been discovered in most parts of the AHDC1 gene, predominantly as frameshift mutations (4) (Figure 1A). However, the exact correlation between these AHDC1 mutation sites and the clinical phenotypes of patients remains incompletely understood. Clinical studies involving 20 individuals carrying 16 different AHDC1 mutations in XGS have suggested a potential association between truncating mutations at the protein's C-terminus and non-verbal disabilities (3). However, it is worth noting that the same recurrent mutations observed in multiple patients exhibit diverse phenotypic variations among different individuals (3). Furthermore, a nonsense mutation at the N-terminus of the AHDC1/Gibbin protein results in a shorter form of the mutant protein, which demonstrates more severe phenotypic effects compared to proteins with C-terminal truncations (5). These observations underscore the phenotypic heterogeneity caused by AHDC1 mutations, which has been well summarized by Khayat et al. (4). Missense mutations in AHDC1 are also likely to produce full-length proteins that could act through similar mechanisms (6,7). Additionally, large de novo deletions encompassing the entire AHDC1 locus have been associated with XGS (8)(9)(10).Disruptions in the 5'UTR region of AHDC1 leading to reduced gene expression have also been documented (11), supporting the hypothesis that AHDC1 haploinsufficiency may contribute to its related developmental disorders. More research is essential to understand the effects of different mutations on AHDC1 expression and the protein's structure and function.Investigating the functional loss or gain due to AHDC1 mutations is crucial for understanding XGS pathogenesis and may aid in therapeutic development and inform research on other developmental disorders. However, correlating specific mutation sites to phenotypic outcomes remains a challenge due to limited understanding and statistical data. Deciphering these complexities will depend on a comprehensive understanding of the full range of functions of the AHDC1/Gibbin protein and a detailed examination of how various mutations affect its activity.The study of AHDC1/Gibbin is fraught with difficulties: the large, 1603-amino-acid protein complicates the understanding of its functional domains, purification of recombinant proteins, crystal structure analysis, and in vitro functional studies. The cellular state of AHDC1/Gibbin (monomeric or multimeric), its nuclear distribution patterns (4), and its interacting partners remain enigmatic, presenting barriers to delineating its role in diseases. Furthermore, a lack of animal models for direct observation and the gene's ubiquitous expression across tissues pose additional challenges in unraveling AHDC1/Gibbin's function. These complexities make it difficult to advance our understanding of AHDC1/Gibbin's role in XGS and beyond.Recently, Collier et al. (12) discovered that AHDC1/Gibbin serves as a crucial controller in mesodermal lineage specification, thus providing a potential framework for understanding the pathogenesis of XGS. Through its interaction with chromatin regulatory factors and DNA methylation, AHDC1/Gibbin plays a pivotal role in preserving accurate chromatin contacts between promoters and enhancers of mesodermal genes during the differentiation process. Consequently, the loss of AHDC1/Gibbin disrupts these chromatin contacts, resulting in the dysregulated expression of mesodermal-specific genes and the consequent abnormal development of the epithelial tissue. However, the mechanism through which AHDC1/Gibbin contributes to chromatin looping has yet to be fully elucidated. Nevertheless, this study is highly commendable as it uncovers a comprehensive molecular landscape of AHDC1/Gibbin during the differentiation of hESC into epithelial lineages.Although this study does not definitively characterize the precise function of AHDC1/Gibbin, it suggests that AHDC1/Gibbin is a crucial player in chromatin structural organization and transcription regulation. It is implicated in the modulation of DNA methylation and chromatin contacts, similar to other chromatin organization regulators such as methyl-CpG binding protein 2 (MECP2) and activity dependent neuroprotective protein (ADNP). However, the specific molecular mechanisms underlying AHDC1/Gibbin's impact on DNA methylation and its interaction with chromatin are still unknown. Furthermore, AHDC1/Gibbin's transcription regulatory and lineage-determining roles are limited to cellular differentiation, similar to MECP2 and ADNP. The interacting protein profiles of AHDC1/Gibbin also resemble those of MECP2 and ADNP. Additionally, the variation in protein localization patterns of AHDC1/Gibbin in the cell nucleus due to different mutations (4) suggests that structural changes in AHDC1/Gibbin protein contribute to XGS pathogenesis, mirroring potential functions similar to MECP2 (13). Therefore, it is reasonable to hypothesize that AHDC1/Gibbin dysfunction could affect specific genes through physical factors in three-dimensional chromatin organization, similar to the role of MECP2 and ADNP. Phenotypic heterogeneity caused by AHDC1 mutations may also potentially stem from differences in chromatin organization and transcriptional expression patterns arising from distinct AHDC1 mutation sites. Future studies might validate this hypothesis by investigating the three-dimensional structure of normal and mutated AHDC1/Gibbin proteins and their impact on chromatin organization.Changes in chromatin structure and DNA methylation have been shown to contribute to the development and progression of various neurological and metabolic disorders, such as epilepsy, Alzheimer's disease, schizophrenia, autism, cancer and obesity. Considering that the AHDC1/Gibbin protein may serve as a regulator of chromatin structure, DNA methylation, and gene transcription, structural and functional deficits in this protein are likely to induce widespread disruptions in gene expression. Support for these notions has been obtained from the work by Collier and colleagues (12), which, when coupled with the globally consistent gene expression pattern of AHDC1 observed across tissues, hints at the potentially extensive pathological reach of AHDC1/Gibbin dysfunction. Current research also supports that AHDC1/Gibbin plays a multifaceted and diverse role. For example, AHDC1 gene mutations have been discovered in patients with syndromic obesity (14). We recently discovered that mice with Ahdc1 deficiency exhibit notable obesity and energy metabolism disruption (15). Additionally, Xia-Gibbs syndrome patients experience both epilepsy and autism (3); whole-genome sequencing has revealed rare AHDC1 germline variants in first-degree relatives of familial pancreatic cancer patients (16); and there is a heightened risk of long-term kidney disease in patients with rare missense variants in AHDC1 (17). Further investigations are imperative to achieve a comprehensive comprehension of AHDC1/Gibbin's involvement in these diverse diseases and to illuminate the complete range of pathological consequences resulting from AHDC1 mutations.Despite the successful generation of an Ahdc1 knockout mouse model by Collier et al. (12), both homozygous and heterozygous mice were unable to survive.Considering that XGS is typically diagnosed after birth and patients can live into adulthood, the availability of a viable animal model is essential for accurately mimicking the natural history of the disease and investigating potential therapeutic approaches. We have established a mouse model with a heterozygous deletion targeting exon 6 of Ahdc1 and found a ~50% reduction in Ahdc1 gene expression (15), using a different strain and breeding method than the Collier's study. While Collier et al. used the C57BL/6J strain for mosaic CRISPR mutants (12), we opted for the C57BL/6N strain and successfully generated heterozygotes through multiple rounds of in vitro fertilization. Our research suggests that this model shows neurobehavioral abnormalities and can partially mimic the phenotype of XGS patients (unpublished).Future studies should focus on creating mouse models with pathogenic mutations and investigating the tissue-specific and adult biological functions of AHDC1/Gibbin through conditional knockouts.In summary, unraveling the molecular mechanism of XGS linked to AHDC1 mutations requires future investigation into AHDC1/Gibbin's structure and function and its mutation-induced dysfunctions using advanced technologies at in vitro, cellular, and animal levels. The disruption of AHDC1/Gibbin protein's role in chromatin structure, DNA methylation, and gene regulation could be a key mechanism underlying XGS. (Figure 1B). Understanding AHDC1/Gibbin's structure and biological functions, as well as the determinants and mechanisms governing its

Hypercholesterolemia is an independent risk factor for cardiovascular disease and lowering circulating levels of low-density lipoprotein cholesterol (LDL-C) can prevent and reduce cardiovascular events. MicroRNA-181d (miR-181d) can reduce the levels of triglycerides and cholesterol esters in cells. However, it is not known whether miR-181d-5p can lower levels of circulating LDL-C. Here, we generated two animal models of hypercholesterolemia to analyze the potential relationship between miR-181d-5p and LDL-C. In hypercholesterolemia model mice, adeno-associated virus (AAV)-mediated liver-directed overexpression of miR-181d-5p decreased the serum levels of cholesterol and LDL-C and the levels of cholesterol and triglyceride in the liver compared with control mice. Target Scan 8.0 indicated Proprotein convertase subtilisin/kexin type 9 (PCSK9) to be a possible target gene of miR-181d-5p, which was confirmed by in vitro experiments. miR-181d-5p could directly interact with both the PCSK9 3'-UTR and promoter to inhibit PCSK9 translation and transcription. Furthermore, Dil-LDL uptake assays in PCSK9 knockdown Huh7 cells demonstrated that miR-181d-5p promotion of LDL-C absorption was dependent on PCSK9. Collectively, our findings show that miR-181d-5p targets the PCSK9 3'-UTR to inhibit PCSK9 expression and to reduce serum LDL-C. miR-181d-5p is therefore a new therapeutic target for the development of anti-hypercholesterolemia drugs.

BackgroundAtherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality globally. Hypercholesterolemia accelerates atherosclerotic development and is an independent modifiable risk factor for ASCVD. Reducing cholesterol levels is effective in preventing ASCVD. Acetyl-L-carnitine (ALC) is an endogenous molecule that plays a primary role in energy metabolism; however, its effect on cholesterol metabolism remains unclear.MethodsWe collected plasma samples and clinical data from 494 individuals with hyperlipidemia. Targeted metabolomics were used to measure plasma ALC levels and explore the association of ALC with clinical cholesterol levels. Additionally, we explored the effects of ALC in cholesterol levels and cholesterol metabolism in a murine hypercholesterolemia model. An LDLR−/− mouse-based atherosclerotic model was established to investigate the roles of ALC on atherosclerotic progression.ResultsPlasma ALC concentrations were significantly negatively correlated with plasma total cholesterol (TC) levels (r = −0.43, p < 0.0001) and low-density lipoprotein cholesterol (LDL-C; r = −0.53, p < 0.0001). Incorporating ALC into the diet significantly reduced plasma TC and LDL-C levels, downregulated genes involved in cholesterol synthesis, such as sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy-3-methyl-glutaryl-CoA reductase, and upregulated low-density lipoprotein receptor expression. ALC supplementation substantially lowered plasma TC levels and inhibited atherosclerosis in LDLR−/− mice.ConclusionALC reduced atherosclerotic plaque formation by lowering plasma cholesterol levels via suppression of SREBP2-mediated cholesterol synthesis, thus suggesting that ALC is a potential therapeutic target for ASCVD.

Microplastics (MPs) is an emerging pollutant potentially harmful to health. Medical practices using plastic devices, such as percutaneous coronary interventions (PCI), may result in MPs entering into the blood. The purpose of this study was to quantify the effect of PCI on microplastic levels in patients' blood. Laser direct infrared (LDIR) was used to detect MPs in the blood of 23 patients before and after PCI. MPs in the water in which devices used in PCI were washed were also examined. The concentration of MPs in the blood was significantly elevated (93.57 ± 35.95 vs. 4.96 ± 3.40 particles/10 mL of blood, P < 0.001) after PCI compared to before, and the increased MPs were polyamide (PA), polyethylene (PE), polyurethane (PU), and polyethylene terephthalate (PET), which was consistent with the types of MPs detected in the device washing water. The maximum diameter of MPs in blood before PCI was 50 µm, whereas after PCI it was 213 µm, and even 336 µm in device washing water. These findings indicated that PCI will cause MPs to enter the blood, and devices used during PCI were a major source, a range of medical practices that use plastic devices may be a new route for MPs to enter the human body.

Objective: Excessive daytime sleepiness (EDS) frequently accompanies obstructive sleep apnea (OSA) and may increase cardiovascular risks. The majority of coronary artery disease (CAD) patients receive understandard treatments, it is not clear whether EDS is associated with increased residual cardiovascular risks in CAD patients with OSA. Method: This study is a prospective cohort study that included 1215 consecutive CAD patients underwent overnight sleep study with a 3.7 year follow-up. Sleepiness was is determined by the Epworth Sleepiness Scale questionnaire. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, stroke, and heart failure. Kaplan-Meier model and Cox proportional hazards models were used to explore the relationship between residual cardiovascular risks and EDS. Result: 1027 cases were eventually enrolled, and a total of 129 patients experienced cardiovascular and cerebrovascular events. Participants with EDS had a higher risk of MACCE compared to those without EDS (17.02% vs. 9.58%, P = 0.005). The presence of EDS is associated with higher incidence of MACCE compared to non-EDS patients (HR 2.833; 95%CI:1.394-5.762; P < 0.001). EDS was significantly associated with increased incidence of MACCE in OSA patients (HR 1.765; 95%CI:1.276-2.543; P = 0.193), while there was no significant association between EDS and cardiovascular risks in non-OSA patients (HR 1.233; 95%CI: 0.893-2.755; P = 0.127). Conclusions: The existence of EDS may lead to increased cardiovascular risks, EDS is associated with increased cardiovascular risks in CAD patients, especially in patients with OSA.

Microplastics are ubiquitous in the environment. Human body can be exposed to microplastics through inhalation and ingestion and some microplastics can enter the blood and accumulate in various tissues and organs throughout the body. Animal experiments have suggested that microplastics may promote atherosclerosis. However, data on microplastics in human arteries and clinical evidence supporting a link between microplastics and atherosclerosis are currently lacking. Pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) was used in this study to detect microplastics in three types of human arteries: coronary and carotid arteries with atherosclerotic plaques, as well as the aorta without plaques. Microplastics were detected in all 17 arterial samples, with an average concentration of 118.66 ± 53.87 μg/g tissue. Four types of microplastics were identified: polyethylene terephthalate (PET, 73.70%), polyamide-66 (PA-66, 15.54%), polyvinyl chloride (PVC, 9.69%), and polyethylene (PE, 1.07%). Most importantly, the concentration of microplastics in arteries containing atherosclerotic plaques, both coronary arteries (156.50 ± 42.14 vs. 76.26 ± 14.86 μg/g tissue, P = 0.039), and carotid arteries (133.37 ± 60.52 vs. 76.26 ± 14.86 μg/g tissue, P = 0.015), was significantly higher than that in aortas which did not contain atherosclerotic plaques, suggesting that microplastics might be associated with atherosclerosis in humans. This study provides valuable data for further hazard assessments of microplastics on human cardiovascular health.

Postoperative atrial fibrillation (POAF) is a common complication after coronary artery bypass grafting (CABG) surgery. Gut microbiota and its metabolites have been implicated in the development of AF. However, whether the gut–host metabolic interaction contributes to POAF is still unknown. This study aimed to investigate the POAF-associated gut microbiota metabolism biomarkers and related risk model. The POAF (N = 30) patients and non-POAF (N = 60) patients from the discovery cohort exhibited significantly different microbiome and metabolome profiles. The differentiated features were mainly implicated in the bile acids (BAs) and short-chain fatty acids metabolism, inflammation, and oxidative stress. Random forest analysis identified the combination of five secondary BAs showed a powerful performance on predicting POAF in the discovery cohort, highlighting significant values of area under the curve (AUC = 0.954) and correct classification rate (CCR, 93.3%). In addition, the five secondary BAs-based risk model also exhibited good performance in differentiating the POAF (N = 114) and non-POAF individuals (N = 253) in an independent validation cohort (AUC = 0.872; CCR = 90.4%). This work revealed perturbed microbial and metabolic traits in POAF, providing potential avenues for the prediction and prevention of POAF after CABG.

Coronavirus disease 2019 (COVID-19) is continuously posing high global public health concerns due to its high morbidity and mortality. This study aimed to construct a convenient risk model for predicting in-hospital mortality of COVID-19 Omicron variant. A total of 1324 hospitalized patients with Omicron variant were enrolled from Beijing Anzhen Hospital. During hospitalization, the Omicron variant mortality rate was found to be 24.4%. Using the datasets of clinical demographics and laboratory tests, three machine learning algorithms, including best subset selection, stepwise selection, and least absolute shrinkage and selection operator regression analyses were employed to identify the potential predictors of in-hospital mortality. The results found that a panel of twenty-four clinical variables (including age, hyperlipemia, stroke, tumor, and several cardiovascular markers) identified by stepwise selection model exhibited significant performances in predicting the in-hospital mortality of COVID-19. The resultant nomogram showed good discrimination, highlighted by the areas under the curve values of 0.88 for 10 days, 0.81 for 20 days, and 0.82 for 30 days, respectively. Furthermore, decision curve analysis showed a significant reliability and precision for the established stepwise selection model. Collectively, this study developed an accurate and convenience risk model for predicting the in-hospital mortality of COVID-19 Omicron.

Microplastics, widely present in the environment, are implicated in disease pathogenesis through oxidative stress and immune modulation. Prevailing research, primarily based on animal and cell studies, falls short in elucidating microplastics' impact on human cardiovascular health. This cross-sectional study detected blood microplastic concentrations in patients presenting with chest pain using pyrolysis–gas chromatography/mass spectrometry and evaluating inflammatory and immune markers through flow cytometry, to explore the potential effects of microplastic on acute coronary syndrome. The study included 101 participants, comprising 19 controls and 82 acute coronary syndrome cases. Notably, acute coronary syndrome patients exhibited elevated microplastic concentrations, with those suffering from acute myocardial infarction presenting higher loads compared to those with unstable angina. Furthermore, patients at intermediate to high risk of coronary artery disease displayed significantly higher microplastic accumulations than their low-risk counterparts. A significant relationship was observed between increased microplastic levels and enhanced IL-6 and IL-12p70 contents, alongside elevated B lymphocyte and natural killer cell counts. These results suggest an association between microplastics and both vascular pathology complexity and immunoinflammatory response in acute coronary syndrome, underscoring the critical need for targeted research to delineate the mechanisms of this association.

BackgroundHigh-fat diet (HFD)-induced hyperlipidemia, which is associated with gut microbiota disturbances, remains a major public health challenge. Glycerolipid metabolism is responsible for lipid synthesis and is thus involved in the development of hyperlipidemia. However, possible association between the HFD-modulated gut microbiome and the glycerolipid metabolism pathway remains unclear.MethodsHamsters were fed a HFD for 4 weeks to establish a hyperlipidemia model. Fecal, plasma and liver samples collected from hamsters fed a HFD or a normal chow diet (NCD) were used for integrative metagenomic and untargeted metabolomic analyses to explore changes in the composition and functions of the gut microbiota, and relevant metabolites. Spearman rank correlation analysis was used to explore correlations between gut microbes and circulating glycerolipid metabolites, gut microbes and lipids, and circulating glycerolipid metabolites and lipids.ResultsThe gut microbial composition of HFD hamsters showed significant alterations at the phylum, genus, and species levels that were skewed toward metabolic disorders compared with that of NCD hamsters. Functional characterization by KEGG analysis identified enrichment of the glycerolipid metabolism pathway in the gut microbiome of HFD hamsters. Plasma and liver metabolomics further indicated the upregulation and enrichment of glycerolipid metabolites in HFD hamsters. The Faecalibaculum, Allobaculum, and Eubacterium genera were positively correlated with plasma glycerolipid metabolites and lipid indices.ConclusionThe findings of this study suggest an association between glycerolipid metabolism and the HFD-modulated gut microbiome that is involved in the development of hyperlipidemia.

BACKGROUND:The effectiveness of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is still uncertain, especially for patients with ischemic left ventricular dysfunction. This study aimed to assess hibernating myocardium (HM), as determined by single-photon emission computed tomography (SPECT) and 18F-FDG positron emission tomography (PET), and to compare the benefits of PCI and optimal medical therapy (OMT). METHODS:A retrospective study collected data from 332 patients with CTO and ischemic left ventricular dysfunction. The study compared patients who underwent PCI or OMT via propensity score matching (PSM) analysis which was performed with a 1:2 matching protocol using the nearest neighbour matching algorithm. The primary endpoint of the study was the occurrence of major adverse cardiac events (MACE), defined as a composite of cardiac death, readmission for worsening heart failure (WHF), revascularization and myocardial infarction (MI). RESULTS:After PSM, there were a total of 246 individuals in the PCI and OMT groups. Following Cox regression, hibernating myocardium/total perfusion defect (HM/TPD) was identified as an independent risk factor (hazard ratio (HR): 1.03, 95% confidence interval (CI): 1.008-1.052, p = .007). The cut-off value of HM/TPD was 38%. The results of the subgroup analysis suggest that for patients with HM/TPD >38%, the OMT group had a greater risk of MACE (p = .035). A sensitivity analysis restricting patients with single-vessel CTO lesions, HM/TPD remained an independent predictor (HR 1.025, 95% CI 1.008-1.043, p = .005). CONCLUSION:HM/TPD is an independent predictor of MACE, and for patients with HM/TPD > 38%, CTO-PCI had a lower risk of MACE compared with OMT. However, further validation is still needed through large-scale studies.

Abdominal aortic aneurysm (AAA) is a potentially life-threatening vascular disease primarily in the male elderly population, but there is a lack of approved medical therapies to prevent the progression and rupture of AAA. Activating Transcription Factor 4 (ATF4) has been established to be involved in cardiovascular diseases, such as heart failure and calcific aortic valve disease. However, the role of ATF4 in the pathogenesis of AAA remains unclear. We found that ATF4 expression was significantly increased in patients with AAA and mouse models of AAA and was mainly confined to macrophages in arteries. ATF4 knockdown significantly attenuated aneurysm formation in experimental mouse model of AAA, while ATF4 overexpression promoted the development of AAA. RNA sequencing suggested that ATF4 was strongly related to the biological function of acute inflammatory response. Macrophages-specific ATF4 knockout significantly reduced the incidence and development of AAA, and decreased M1 polarization of macrophages in mice. Sphingomyelin phosphodiesterase 3 (SMPD3), a regulator of inflammatory responses in monocytes/macrophages, has been identified as a target gene of ATF4 through RNA sequencing, ChIP sequencing, and standard ChIP analyses. ATF4 induces M1 polarization of macrophages through the activation of SMPD3, thereby promoting inflammatory responses. Together, these results suggest that ATF4 mediated macrophage M1 polarization by regulating the expression of target genes SMPD3, leading to an increased inflammatory response, which further promotes the formation and development of AAA. These findings suggest ATF4 may be a new therapeutic target for AAA.

Cardiovascular disease is the leading cause of morbidity and mortality worldwide, and dyslipidemia is one of the major risk factors [...]