Targeted drug delivery systems for atherosclerosis

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 23, 2025

Atherosclerosis is a complex cardiovascular disease driven by multiple factors, including aging, inflammation, oxidative stress, and plaque rupture. The progression of this often covert, emphasizing the need for early biomarkers effective intervention measures. In recent years, advancements in therapeutic strategies have highlighted potential targeting specific processes atherosclerosis, such as localization, macrophage activity, key enzymes. Based on this, review discusses role targeted drugs treatment atherosclerosis. It also focuses their clinical efficacy anti-atherosclerosis ability to provide more precise approaches. findings underscore that future research can concentrate exploring newer drug delivery systems further refine enhance long-term dynamic management

Язык: Английский

---

An integrative analysis of single-cell and bulk transcriptome and bidirectional mendelian randomization analysis identified C1Q as a novel stimulated risk gene for Atherosclerosis

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Дек. 21, 2023

Background The role of complement component 1q (C1Q) related genes on human atherosclerotic plaques (HAP) is less known. Our aim to establish C1Q associated hub using single-cell RNA sequencing (scRNA-seq) and bulk analysis diagnose predict HAP patients more effectively investigate the association between (ischemic stroke) bidirectional Mendelian randomization (MR) analysis. Methods scRNA-seq bulk-RNA data were download from Gene Expression Omnibus (GEO) database. C1Q-related was screened GBM, LASSO XGBoost algorithms. We built machine learning models distinguish types atherosclerosis generalized linear receiver operating characteristics (ROC) analyses. Further, we scored HALLMARK_COMPLEMENT signaling pathway ssGSEA confirmed gene expression through qRT-PCR in RAW264.7 macrophages apoE-/- mice. Furthermore, risk assessed MR analysis, with as exposure ischemic stroke (IS, large artery atherosclerosis) outcomes. Inverse variance weighting (IVW) used main method. Results utilized dataset (GSE159677) identify 24 cell clusters 12 types, revealed seven DEGs both GEO datasets. then select C1QA C1QC DEGs. findings indicated that training validation cohorts had satisfactory diagnostic accuracy for identifying HPAs. Additionally, SPI1 a potential TF responsible regulating two HAP. further correlated activated C1QC. high levels C1QA, ox-LDL-treated mice qPCR. results there positive genetic IS, evidenced by an odds ratio (OR) 1.118 (95%CI: 1.013–1.234, P = 0.027). Conclusion authors have developed validated novel signature comprising HAP, while has provided evidence supporting favorable IS.

Язык: Английский

---

LY86 facilitates ox-LDL-induced lipid accumulation in macrophages by upregulating SREBP2/HMGCR expression

BMC Cardiovascular Disorders, Год журнала: 2024, Номер 24(1)

Опубликована: Май 31, 2024

Abstract LY86, also known as MD1, has been implicated in various pathophysiological processes including inflammation, obesity, insulin resistance, and immunoregulation. However, the role of LY86 cholesterol metabolism remains incompletely understood. Several studies have reported significant up-regulation mRNA atherosclerosis; nevertheless, regulatory mechanism by which is involved this disease unclear. In study, we aimed to investigate whether affects ox-LDL-induced lipid accumulation macrophages. Firstly, confirmed that indeed process atherosclerosis found high expression levels human atherosclerotic plaque tissue. Furthermore, our findings suggest may mediate intracellular induced ox-LDL through SREBP2/HMGCR pathway. This could be associated with increased synthesis resulting from enhanced endoplasmic reticulum stress response.

Язык: Английский

---

Identification and experimental validation of KMO as a critical immune-associated mitochondrial gene in unstable atherosclerotic plaque

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 18, 2024

Abstract Background The heightened risk of cardiovascular and cerebrovascular events is associated with the increased instability atherosclerotic plaques. However, lack effective diagnostic biomarkers has impeded assessment plaque currently. This study was aimed to investigate identify hub genes unstable plaques through integration various bioinformatics tools, providing novel insights into detection treatment this condition. Methods Weighted Gene Co-expression Network Analysis (WGCNA) combined two machine learning methods were used strongly instability. cell-type identification by estimating relative subsets RNA transcripts (CIBERSORT) method utilized assess immune cell infiltration patterns in atherosclerosis patients. Additionally, Set Variation (GSVA) conducted potential biological functions, pathways, mechanisms To further validate efficiency expression genes, immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA) performed on collected human carotid blood samples. Immunofluorescence co-staining also confirm association between cells, as well their colocalization mitochondria. Results CIBERSORT analysis demonstrated a significant decrease CD8 T cells an obvious increase M0 macrophages patients atherosclerosis. Subsequently, highly relevant modules (blue green) identified. Through intersection mitochondria-related 50 crucial Further employing least absolute shrinkage selection operator (LASSO) logistic regression support vector recursive feature elimination (SVM-RFE) algorithms revealed six significantly Among them, NT5DC3 , ACADL SLC25A4 ALDH1B1 MAOB exhibited positive correlations negative macrophages, while kynurenine 3-monooxygenas ( KMO ) correlation cells. IHC RT-qPCR analyses samples, ELISA upregulation expression, along decreased both stable samples compared control among three key mentioned above, only showed Furthermore, tissues cultured mouse macrophage lines assessed using immunofluorescence techniques. Finally, lentivirus-mediated silencing successfully transduced aortas high-fat-fed ApoE-/- mice, results indicating that attenuated formation promoted stability mice. Conclusions suggest mitochondria-targeted gene holds promise valuable biomarker for assessing

Язык: Английский

---

Identification and validation of immune cells and hub genes alterations in recurrent implantation failure: A GEO data mining study

Frontiers in Genetics, Год журнала: 2023, Номер 13

Опубликована: Янв. 9, 2023

Introduction: Recurrent implantation failure (RIF) is a distressing problem in assisted reproductive technology (ART). Immunity plays vital role recurrent occurrence and development, but its underlying mechanism still needs to be fully elucidated. Through bioinformatics analysis, this study aims identify the RIF-associated immune cell types immune-related genes. Methods: The differentially expressed genes (DEGs) were screened based on Gene Expression Omnibus (GEO) datasets. Then, enrichment analysis protein-protein interaction (PPI) conducted with DEGs. clarified by combining single sample gene set (ssGSEA) CIBERSORT. Differentially types-related modules identified weighted co-expression network (WGCNA) local maximal quasi-clique merger (lmQCM) analysis. overlapping between DEGs contained mentioned above delineated as candidate hub validated another two external Finally, microRNAs (miRNAs) long non-coding RNAs (lncRNAs) that interacted predicted, competing endogenous RNA (ceRNA) regulatory was structured. Results: In present study, we collected 324 RIF control group, which functions mainly enriched signaling pathways. Regarding differential types, group had higher proportion of activated memory CD4 T cells lower γδ endometrial tissue. three (ALOX5AP, SLC7A7, PTGS2) verified effectively discriminate from individuals specificity rate 90.8% sensitivity 90.8%. addition, constructed key ceRNA expected mediate molecular mechanisms RIF. Conclusion: Our intricate correlation provided new offer promising diagnostic therapeutic targets for

Язык: Английский

---

Nonnegative matrix factorization analysis and multiple machine learning methods identified IL17C and ACOXL as novel diagnostic biomarkers for atherosclerosis

BMC Bioinformatics, Год журнала: 2023, Номер 24(1)

Опубликована: Май 12, 2023

Abstract Background Atherosclerosis is the common pathological basis for many cardiovascular and cerebrovascular diseases. The purpose of this study to identify diagnostic biomarkers related atherosclerosis through machine learning algorithm. Methods Clinicopathological parameters transcriptomics data were obtained from 4 datasets (GSE21545, GSE20129, GSE43292, GSE100927). A nonnegative matrix factorization algorithm was used classify arteriosclerosis patients in GSE21545 dataset. Then, we identified prognosis-related differentially expressed genes (DEGs) between subtypes. Multiple methods detect pivotal markers. Discrimination, calibration clinical usefulness predicting model assessed using area under curve, plot decision curve analysis respectively. expression level feature validated GSE100927. Results 2 molecular subtypes identified, 223 DEGs identified. These are not only epithelial cell proliferation, mitochondrial dysfunction, but also immune pathways. Least absolute shrinkage selection operator, random forest, support vector machine- recursive elimination show that IL17C ACOXL as markers atherosclerosis. prediction displayed good discrimination calibration. Decision showed clinically useful. Moreover, verified other 3 GEO datasets, have predictive performance. Conclusion associated with higher incidence ischemic events.

Язык: Английский

---

ITGB2 is a central hub-gene associated with inflammation and early fibro-atheroma development in a swine model of atherosclerosis

Atherosclerosis Plus, Год журнала: 2023, Номер 54, С. 30 - 41

Опубликована: Ноя. 16, 2023

The complex dynamic interplay between different biological pathways involved in atherosclerosis development has rendered the identification of specific therapeutic targets a challenging quest. We aimed to identify genes and mechanistic associated with early fibro-atheromas swine model atherosclerosis.The Wisconsin Miniature Swine™ Familial Hypercholesterolemia (WMS-FH, n = 11) genetically related WMS controls (WMS-N, were used. infrarenal aorta was harvested from both groups for histopathologic transcriptomic profiling at 12 months. Bioinformatic analysis performed hub central disease pathophysiology. expression ITGB2, top ranked gene, manipulated cell culture interconnected tested.Fibro-atheromatous lesions documented all WMS-FH aortic tissues displayed internal elastic lamina (IEL) disruption, significant reduction myofibroblast presence disorganized collagen deposition. No observed control group. A total 266 differentially expressed (DEGs) upregulated tissues, while 29 downregulated. Top identified included C1QA, LCP2, SPI1, CSF1R, C5AR1, CTSS, MPEG1, C1QC, CSF2RB. Overexpression ITGB2 resulted elevated other porcine endothelial cells.In translational atherosclerosis, as gene inflammation fibroatheroma making it potential target this stage disease.

Язык: Английский

---

Novel immune cell infiltration-related biomarkers in atherosclerosis diagnosis

PeerJ, Год журнала: 2023, Номер 11, С. e15341 - e15341

Опубликована: Май 1, 2023

Background Immune cell infiltration (ICI) has a close relationship with the progression of atherosclerosis (AS). Therefore, current study was aimed to explore role genes related ICI and investigate potential mechanisms in AS. Methods Single-sample gene set enrichment analysis (ssGSEA) applied immune AS controls. Genes infitration were mined by weighted co-expression network (WGCNA). The function those analyzed analyses Kyoto Encyclopedia Genomes (KEGG) Gene Ontology (GO). interactions among visualized protein-protein interaction (PPI) network, followed identification hub through Cytoscape software. A receiver operating characteristic (ROC) plot generated assess performance diagnosis. expressions measured reverse transcription quantitative real-time PCR (RT-qPCR) human leukemia monocyticcell line (THP-1) derived foam cells macrophages, which mimic control, respectively. Results We observed that proportions 27 significantly elevated Subsequent integrative differential expression WGCNA identified 99 cell-related differentially expressed (DEGs) between control. Those DEGs associated tryptophan metabolism extracellular matrix (ECM)-related functions. Moreover, constructing PPI we found 11 pattern ROC two independent datasets showed calsequestrin 2 (CASQ2), nexilin F-Actin binding protein (NEXN), metallopeptidase 12 (MMP12), C-X-C motif chemokine ligand 10 (CXCL10), phospholamban (PLN), heme oxygenase 1 (HMOX1), ryanodine receptor (RYR2), chitinase 3 like (CHI3L1), 9 (MMP9), actin alpha cardiac muscle (ACTC1) had good distinguishing from control samples. Furthermore, biomarkers shown be correlated angiogenesis checkpoints. In addition, 239 miRNAs 47 factor s (TFs), may target regulate their expressions. Finally, RT-qPCR results consistent sequencing results.

Язык: Английский

---

Identification of the shared mechanisms and common biomarkers between Sjögren’s syndrome and atherosclerosis using integrated bioinformatics analysis

Frontiers in Medicine, Год журнала: 2023, Номер 10

Опубликована: Авг. 31, 2023

Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by exocrine and extra-glandular symptoms. The literature indicates that SS an independent risk factor for atherosclerosis (AS); however, its pathophysiological mechanism remains undetermined. This investigation aimed to elucidate the crosstalk genes pathways influencing pathophysiology of AS via bioinformatic analysis microarray data.Microarray datasets (GSE40611) (GSE28829) were retrieved from Gene Expression Omnibus (GEO) database. Differentially expressed (DEGs) acquired using R software's "limma" packages, functions common DEGs determined Ontology Kyoto Encyclopedia analyses. protein-protein interaction (PPI) was established STRING hub assessed cytoHubba plug-in validated external validation (GSE84844 SS; GSE43292 AS). set enrichment (GSEA) immune infiltration also conducted.Eight 8 identified intersection four topological algorithms in PPI network. Four (CTSS, IRF8, CYBB, PTPRC) then verified as important cross-talk between with area under curve (AUC) ≥0.7. Furthermore, revealed lymphocytes macrophages are essentially linked pathogenesis SS. Moreover, shared enriched multiple metabolisms disease-related pathways, evidenced GSEA analyses.This first study explore AS. key genes, including CTSS, PTPRC, associated These their correlation cells could be potential diagnostic therapeutic target.

Язык: Английский

---

Design of siRNAs Against Immune-Implicated Atherosclerosis Genes: Computational Study

Turkish computational and theoretical chemistry/Turkish computational and theoretical chemistry :, Год журнала: 2023, Номер 8(2), С. 12 - 18

Опубликована: Июль 5, 2023

Atherosclerosis is a chronic, immune-implicated, disease with high numbers of mortality globally. The aim the current study to target these genes by specific siRNA utilizing bioinformatics tools. Eight siRNAs were designed via RNAxs from C1QA and ITBG2 gene sequences retrieved NCBI database. GC% Tm calculated through OligoCalc web interface. In addition, hybridization energy corresponding as well docking argonaute 2 protein performed using DuplexFold HDock. exhibited acceptable GC content values. Besides, scores highly significant block expression mentioned genes. conclusion, are superior candidates for silencing immune-mediated atherosclerotic which deserve further consideration.

Язык: Английский

---