Background and objectives: Phenotypic switching in vascular smooth muscle cells (VSMCs) has been linked to aortic aneurysm, but the phenotypic landscape in aortic aneurysm is poorly understood. The present study aimed to analyse the phenotypic landscape, phenotypic differentiation trajectory, and potential functions of various VSMCs phenotypes in aortic aneurysm. Methods: Single-cell sequencing data of 12 aortic aneurysm samples and 5 normal aorta samples (obtained from GSE166676 and GSE155468) were integrated by the R package Harmony. VSMCs were identified according to the expression levels of ACTA2 and MYH11. VSMCs clustering was determined by the R package ‘Seurat’. Cell annotation was determined by the R package ‘singleR’ and background knowledge of VSMCs phenotypic switching. The secretion of collagen, proteinases, and chemokines by each VSMCs phenotype was assessed. Cell‒cell junctions and cell–matrix junctions were also scored by examining the expression of adhesion genes. Trajectory analysis was performed by the R package ‘Monocle2’. qPCR was used to quantify VSMCs markers. RNA fluorescence in situ hybridization (RNA FISH) was performed to determine the spatial localization of vital VSMCs phenotypes in aortic aneurysms. Results: A total of 7150 VSMCs were categorize into 6 phenotypes: contractile VSMCs, fibroblast-like VSMCs, T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs. The proportions of T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs were significantly increased in aortic aneurysm. Fibroblast-like VSMCs secreted abundant amounts of collagens. T-cell-like VSMCs and macrophage-like VSMCs were characterized by high chemokine levels and proinflammatory effects. Adipocyte-like VSMCs and mesenchymal-like VSMCs were associated with high proteinase levels. RNA FISH validated the presence of T-cell-like VSMCs and macrophage-like VSMCs in the tunica media and the presence of mesenchymal-like VSMCs in the tunica media and tunica adventitia. Conclusion: A variety of VSMCs phenotypes are involved in the formation of aortic aneurysm. T-cell-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs play pivotal roles in this process.

Background Aortic aneurysm has a subtle onset, high rupture mortality, rapid progression in younger individuals, and increasing annual mortality rates. Our study aimed to estimate the global burden and trends of early-onset aortic aneurysm from 1990 to 2021. Methods Participants aged 15–39 years from 204 countries and regions (Global Burdern of Disease, GBD) from 1990 to 2021.The primary assessment indicators include age-standardized death rates (ASDR), age-standardized disability-adjusted life years rates (ASDALYR), annual average percent change (AAPC), attributable risk factor proportions, slope index, concentration index, and predictive model for early-onset aortic aneurysm. Results From 1990 to 2021, the ASDR for aortic aneurysm in adolescents and young adults increased from 0.12 (95% confidence interval [CI] 0.11, 0.14) to 0.13 (0.11, 0.14) per 100,000 population, with an AAPC of 0.08% (-0.08%, 0.25%). The ASDALYR rose from 7.25 (6.52, 8.30) to 7.35 (6.51, 8.37), with an AAPC of 0.07% (-0.09%, 0.23%). Both ASDR and ASDALYR are higher in males than females, with a declining trend in females. Higher Socio-Demographic Index (SDI) countries exhibit higher ASDR and ASDALYR compared to lower SDI countries, with a continuous decline observed in high SDI nations. Smoking remains the top risk factor, with population growth being the primary driver. Models predict a global increase in aortic aneurysm deaths, predominantly among males. Conclusion The overall burden of early-onset aortic aneurysms has exhibited an increasing trend over the last three decades, especially in lower SDI countries. There is an urgent need to develop targeted prevention and control strategies across different regions and countries worldwide.

Background: Atherosclerosis (AS) is a chronic arterial pathology and a leading cause of vascular disease-related mortality. Fatty streaks in the arterial wall develop into atherosclerosis and characteristic plaques. Clinical interventions typically involve lipid-lowering medications and drugs for stabilizing vulnerable plaques, but no direct therapeutic agent specifically targets atherosclerosis. Garlic, also locally known as DASUAN, is recognized as a widely sold herbal dietary supplement esteemed for its cardiovascular benefits. However, the specific mechanisms of garlic’s anti-atherosclerotic effects remain unclear.Aims: This study aims to elucidate the pharmacological mechanisms through which garlic ameliorates atherosclerosis.Methods: The study identified the major active components and targets of garlic by screening the TCMSP, TCM-ID, and, ETCM databases. Atherosclerosis-associated targets were obtained from the DisGeNET, GeneCards, and DiGSeE databases, and garlic intervention targets were determined through intersection. Utilizing the intersected genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using R software. A garlic component-disease target network was constructed using Cytoscape. RNA-seq datasets from the GEO database were utilized to identify differentially expressed genes (DEGs) associated with atherosclerosis. The target genes were intersected with DEGs and the FerrDb (ferroptosis database). Molecular docking predicted the binding interactions between active components and the core targets. In vitro and in vivo experiments validated the identified core targets.Results: The integration of garlic drug targets with atherosclerotic disease targets identified 230 target genes. Intersection with RNA-seq DEGs revealed 15 upregulated genes, including 8 target genes related to ferroptosis. Molecular docking indicated favorable affinities between garlic active components [Sobrol A, (+)-L-Alliin, Benzaldoxime, Allicin] and target genes (DPP4, ALOX5, GPX4). Experimental validation showed that GARLIC reduces the expression of ferroptosis-related genes in AS, suggesting its therapeutic potential through the regulation of ferroptosis.Conclusion: Garlic ameliorates atherosclerosis by targeting intra-plaque ferroptosis and reducing lipid peroxidation. These findings provide novel insights into the pharmacological mechanisms underlying the efficacy of garlic in treating AS.

Abdominal aortic aneurysm (AAA) is a serious cardiovascular disease associated with chronic inflammation. The purpose of this study was to use the Olink proteomics to reveal serum inflammatory markers in AAA. We examined the expression levels of 92 inflammation-related proteins in patients with AAA (n = 18) and healthy individuals (n = 10) using the Olink proximity extension assay (PEA) inflammatory plate. Olink proteomics identified 38 differential proteins. Combined analysis of Olink proteomics and GSE183464 showed interleukin-6 (IL-6) and tumor necrosis factor receptor superfamily member 9 (TNFRSF9) were upregulated at both gene and protein levels in AAA patients. The ELISA results were consistent with the Olink proteomics results, and the receiver operating characteristic (ROC) curve analysis revealed that the binding of TNFRSF9 and IL-6 has high diagnostic value (Olink AUC = 0.9056; ELISA AUC = 0.950). Subsequently, elevated TNFRSF9 expression in AAA was confirmed by animal models, suggesting that TNFRSF9 may serve as a potential biomarker for AAA.

Notably, the C‐X‐C Motif Chemokine Ligand 12/C‐X‐C Chemokine Receptor Type 4 (CXCL12/CXCR4) signalling pathway's activation is markedly increased in a mouse model of abdominal aortic aneurysms (AAA). Nonetheless, the precise contribution of this pathway to AAA development remains to be elucidated. The AAA mouse model was induced by local incubation with elastase and oral administration of β‐aminopropionitrile. The activity level of the CXCL12/CXCR4 axis was evaluated in both human AAA patients and the mouse model. Smooth muscle cell lineage tracing determined the expression and localisation of CXCR4 in normal aorta and AAA tissue. By transfecting the MiR206‐3p sponge to reduce the level of MiR206‐3p in AAA, the effects of the CXCL12/CXCR4 pathway on AAA progression as well as the apoptosis and phenotypic transformation of vascular smooth muscle cells (VSMCs) were studied in vivo and in vitro. Single‐cell RNA sequencing analysis, serum ELISA, and in vivo experiments indicate a pronounced activation of the CXCL12/CXCR4 axis in both AAA patients and the mouse model. Specific blocking of the CXCL12/CXCR4 axis significantly inhibited further expansion and rupture of the abdominal aorta and reduced the infiltration of inflammatory cells in the aorta and inhibited the phenotypic transformation of contractile VSMCs into a macrophage‐like state. Our findings propose that MiR206‐3p sponge represents an innovative therapeutic strategy to attenuate AAA progression and rupture risk, primarily through the suppression of the CXCL12/CXCR4 signalling pathway.

Lower extremity peripheral artery disease (PAD) is a growing global health problem. New methods to diagnose PAD have been explored in recent years. At present, the majority of imaging methods for PAD focus on the macrovascular blood flow, and the exploration of microcirculation and tissue perfusion of PAD remains largely insufficient. In this report, we applied three new imaging technologies, i.e., second near-infrared region (NIR-II, 900–1,880 nm wavelengths) imaging, optical coherence tomography angiography (OCTA), and laser speckle flowgraphy (LSFG), in a PAD patient with a healthy human subject as control. Our results showed that the PAD patient had poorer tissue perfusion than the control without observed adverse effects. Moreover, compared with the first near-infrared region (NIR-I, 700–900 nm wavelengths) imaging results, NIR-II imaging had a higher signal-to-background ratio and resolution than NIR-I imaging and detected microvessels that were not detected by NIR-I imaging. These observations suggested that NIR-II imaging, OCTA, and LSFG are potentially safe and effective methods for diagnosing PAD.