Arteriosclerosis, Thrombosis, and Vascular Biology最新文献

{"title":"Metabolites Associated With Long-Term Risk of Peripheral Artery Disease: The ARIC Study.","authors":"Eyram Cyril Bansah, Xiao Hu, Shoshana H Ballew, Morgan E Grams, Vijay Nambi, Elizabeth Selvin, Josef Coresh, Eric Boerwinkle, Bing Yu, Kunihiro Matsushita","doi":"10.1161/ATVBAHA.126.324549","DOIUrl":"10.1161/ATVBAHA.126.324549","url":null,"abstract":"<p><strong>Background: </strong>Lower extremity peripheral artery disease (PAD) is a major contributor to cardiovascular morbidity and mortality; however, the metabolic pathways underlying disease development and progression are poorly understood.</p><p><strong>Methods: </strong>We conducted a prospective cohort study of 3759 participants from the ARIC study (Atherosclerosis Risk in Communities; mean age, 53.5 years; 60% women; 62% Black participants) with untargeted metabolomic profiling at baseline (1987-1989). Incident PAD (458 cases) and its severe form with rest pain or tissue loss, critical limb ischemia (CLI; 135 cases), were identified through hospitalization codes over a median follow-up of 27 years. We used Cox regression with adjustment for traditional risk factors and accounted for multiple testing using a false discovery rate correction at a threshold of 0.05. Risk prediction improvement was evaluated using Harrell C statistics and the net reclassification improvement.</p><p><strong>Results: </strong>Thirteen metabolites were significantly associated with incident PAD and primarily reflected dysregulated glycemic control, impaired redox balance, and altered lipid remodeling (eg, higher levels of mannose and lower levels of 1,5-anhydroglucitol, gamma-glutamyl dipeptides, and lysophospholipids). For CLI, 18 metabolites were identified, 11 of which were unique to CLI and reflected intensified oxidative and bioenergetic stress (eg, homocitrulline, arabonate, and 1-linoleoylglycerol). Metabolites significantly improved risk prediction for PAD beyond traditional risk factors (∆C statistic, 0.017 [95% CI, 0.008-0.025] from a base C statistic of 0.770; net reclassification improvement, 0.053 [95% CI, 0.018-0.083]) and particularly CLI (∆C statistic, 0.041 [95% CI, 0.018-0.064] from a base C statistic of 0.823; net reclassification improvement, 0.176 [95% CI, 0.085-0.268]).</p><p><strong>Conclusions: </strong>Distinct metabolomic profiles were associated with incident PAD and CLI years before clinical onset, highlighting dysregulated glycemic control, impaired redox balance, and altered lipid remodeling as key underlying pathways. These findings suggest that circulating metabolites may serve as early indicators of metabolic health relevant to PAD risk identification and progression to advanced disease.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324549"},"PeriodicalIF":8.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MLL1 Regulates T-Cell Phenotype via Notch Signaling During Abdominal Aortic Aneurysm Development.","authors":"Xiaobing He, Nicholas Juriga, Brennan Callow, Sama Salih, Amrita Joshi, Rachael Bogle, Lam C Tsoi, Andrea T Obi, Johann E Gudjonsson, Katherine A Gallagher, Frank M Davis","doi":"10.1161/ATVBAHA.126.324552","DOIUrl":"10.1161/ATVBAHA.126.324552","url":null,"abstract":"<p><strong>Background: </strong>Abdominal aortic aneurysms (AAA) are characterized by progressive pathological vascular remodeling and a dysregulated immune microenvironment marked by an imbalance between anti-inflammatory regulatory T cells and proinflammatory T helper 17 (Th17) cells within the aortic wall. The molecular mechanisms governing CD4⁺ (cluster of differentiation) T-cell differentiation during AAA development remain incompletely defined. MLL1 (mixed lineage leukemia 1), a histone methyltransferase, has recently been shown to modulate T-cell lineage commitment through epigenetic regulation of transcriptional programs in multiple inflammatory diseases. We, therefore, sought to determine whether MLL1 promotes Th17 polarization during AAA development and to identify signaling pathways through which MLL1 regulates CD4⁺ T-cell infiltration and phenotype.</p><p><strong>Methods: </strong>Single-cell RNA-sequencing was performed on human AAA and nonaneurysmal aortic tissues. Two murine AAA models were utilized: AngII (angiotensin II) infusion with adeno-associated virus-mediated PCSK9 (proprotein convertase subtilisin/kexin type 9) gain-of-function expression and topical porcine pancreatic elastase application in C57BL/6J mice. Mice with CD4⁺ T-cell-specific deletion of Notch signaling (<i>DNMAML</i>^<i>fl/fl</i><i>CD4</i>^<i>cre+</i>), Notch1 (<i>Notch1</i>^<i>fl/fl</i><i>CD4</i>^<i>cre+</i>), or MLL1 (<i>Mll1</i>^<i>fl/fl</i><i>CD4</i>^<i>cre+</i>) were subjected to AngII infusion, and aneurysm diameter was quantified. CD4⁺ T cells were isolated by magnetic-activated cell sorting for gene expression analysis and flow cytometric phenotyping. Chromatin immunoprecipitation assessed H3K4 trimethylation enrichment at target gene promoters.</p><p><strong>Results: </strong>Single-cell sequencing of human AAA tissue demonstrated marked upregulation of MLL1 and Notch1 signaling in CD4⁺ T cells compared with controls. Both human AAA and murine AngII-induced AAA CD4⁺ T cells exhibited a predominant Th17 phenotype with increased MLL1 expression. Chromatin immunoprecipitation analysis revealed enhanced MLL1-mediated H3K4 trimethylation enrichment at the Notch1 promoter. Mice deficient in CD4⁺ Th-cell Notch signaling (<i>DNMAML</i>^<i>fl/fl</i><i>CD4</i>^<i>cre+</i> or <i>Notch1</i>^<i>fl/fl</i><i>CD4</i>^<i>cre+</i>) or MLL1 (<i>Mll1</i>^<i>fl/fl</i><i>CD4</i>^<i>cre+</i>) displayed a significant reduction in aneurysm formation, decreased Th17 activity, and increased regulatory T cell expression.</p><p><strong>Conclusions: </strong>MLL1 epigenetically regulates Notch1 signaling to drive pathogenic Th17 polarization during AAA development. Targeting the MLL1 axis may represent a novel therapeutic strategy to limit aneurysmal progression.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324552"},"PeriodicalIF":8.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13496003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypermetabolic State Drives Platelet Dysfunction in Human and Mouse Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"Francesca Maiorca, Annamaria Sabetta, Moris Sangineto, Davide Pallucci, Océane Dufies, Valentina Poli, Marco Di Gioia, Tania D'Amico, Marzia Miglionico, Ludovica Lombardi, Martina Ciarnelli, Gianluca Signorile, Giulia D'Amati, Giulio Francesco Romiti, Roberto Cangemi, Marcella Visentini, Valeria Raparelli, Gaetano Serviddio, Stefania Basili, Ivan Zanoni, Lucia Stefanini","doi":"10.1161/ATVBAHA.126.325001","DOIUrl":"https://doi.org/10.1161/ATVBAHA.126.325001","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing health concern given rising global prevalence, limited diagnostic and therapeutic tools, and strong association with cardiovascular disease. Platelets and oxidized phospholipids have been implicated in MASLD pathogenesis; however, the drivers and activities of platelets in MASLD remain overlooked.</p><p><strong>Methods: </strong>We conducted a cross-sectional study to determine platelet metabolic and functional states in MASLD and to investigate whether oxidized phospholipids, which accumulate during MASLD, contribute to platelet dysfunction. The study included age-matched individuals with simple steatosis (n=42), steatohepatitis (n=28), metabolic dysfunction-associated cirrhosis (n=16), and controls without steatosis (n=23). Platelet function and metabolism were characterized by flow cytometry and Seahorse analysis. In vivo markers of platelet activation and plasma oxidized low-density lipoprotein were quantified by ELISA. The causal relationship between oxidized phospholipids and the platelet phenotype was investigated by comparing Ldlr^-/- mice fed an Amylin Liver NASH diet to Amylin Liver NASH-fed E06-scFv/Ldlr^-/-, transgenic mice that express a natural antibody (E06) that neutralizes oxidized phospholipids.</p><p><strong>Results: </strong>We report that, since early MASLD in vivo markers of platelet secretion were elevated in plasma and platelets displayed a heightened metabolic activity. In advanced MASLD, associated with MASH and cirrhosis, platelets were refractory to G-protein-coupled receptor stimulation, but more responsive to GPVI stimulation, promoting a secretory and procoagulant phenotype. Platelet dysfunction correlated with increased platelet mitochondrial activity and with blood levels of oxidized low-density lipoprotein, a major source of oxidized lipids. Ex vivo, the oxidized phospholipid oxPAPC recapitulated the increased mitochondrial activity and functional reprogramming observed in MASH platelets. In a mouse model of MASLD, neutralization of oxidized phospholipids partially mitigated diet-induced platelet dysfunction and binding to liver macrophages.</p><p><strong>Conclusions: </strong>In MASLD, we observed heightened platelet metabolic activity and changes in platelet reactivity, providing the basis to target platelet dysfunction for preventing hepatic and extra-hepatic complications of MASLD.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT05128253.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Na/K-ATPase Signaling in Adipocytes Promotes Atherosclerosis.","authors":"Bruno De Souza Goncalves, Yaxin Wang, Sneha S Pillai, Quoc Quang Luu, Hortense Triniac, Hari Vishal Lakhani, Muhammad A Chaudhry, Ze Zheng, Joseph I Shapiro, Roy L Silverstein, Komal Sodhi, Yiliang Chen","doi":"10.1161/ATVBAHA.126.325070","DOIUrl":"10.1161/ATVBAHA.126.325070","url":null,"abstract":"<p><strong>Background: </strong>Adipocyte dysfunction is closely associated with oxidative stress and chronic inflammation, which contribute to systemic metabolic disturbances and atherosclerosis. We previously identified the NKA (Na/K-ATPase) α1 subunit as a signal transducer that activates Src-family kinases and promotes oxidative stress and inflammation in various cell types, including adipocytes and macrophages. NaKtide, a peptide inhibitor of NKA signaling, has been shown to reduce systemic oxidative stress and inflammation in vivo. In this study, we investigated the role of adipocyte-specific NKA signaling in atherosclerosis.</p><p><strong>Methods: </strong>Adipocyte-specific NaKtide was delivered to <i>Apoe</i>^-/- mice using a lentiviral vector under the adiponectin promoter. The mice were then fed a Western diet for 12 weeks to induce atherosclerosis and then assessed for atherosclerotic plaque burden in the aortic arch and at the level of the aortic sinus. Inflammatory and oxidative stress markers were analyzed in adipose tissue and plasma.</p><p><strong>Results: </strong>Adipocyte-specific NaKtide reduced atherosclerotic plaque area by 67% in the aortic arch and by 48% in the aortic sinus. CD68+ (cluster of differentiation 68) macrophage content and α-SMA+ (α-smooth muscle actin) smooth muscle cell content in the aortic sinus were decreased by 45% and 53%, respectively. These vascular improvements were accompanied by dampened adipose tissue inflammation and oxidative stress, improved glucose tolerance, and reduced systemic inflammation.</p><p><strong>Conclusions: </strong>These findings highlight a critical contributing role for adipocyte NKA signaling in atherosclerosis, suggesting an important endocrine and paracrine influence of adipose tissue on large artery atherogenesis and supporting the therapeutic potential of targeting NKA in cardiometabolic disease.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e325070"},"PeriodicalIF":8.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Brain Structure and Neuropsychological Function With Artificial Intelligence Estimates of Biological Vascular Age.","authors":"Leroy L Cooper, Ayantika Banerjee, Alexa S Beiser, Sokratis Charisis, David J Hamel-Sellman, Timothy J Korzinski, Emelia J Benjamin, Naomi M Hamburg, Ramachandran S Vasan, Sudha Seshadri, Gary F Mitchell","doi":"10.1161/ATVBAHA.126.325247","DOIUrl":"10.1161/ATVBAHA.126.325247","url":null,"abstract":"<p><strong>Background: </strong>Accelerated vascular aging, assessed as artificial intelligence-based vascular age (AIVA), is associated with small vessel disease that may impact brain structure and neuropsychological function.</p><p><strong>Methods: </strong>In a cross-section of Framingham Heart Study participants, AIVA was estimated using a validated convolutional neural network trained to predict carotid-femoral pulse wave velocity from a normalized pressure waveform. Brain structure was assessed using magnetic resonance imaging with diffusion tensor imaging, and neuropsychological function was assessed using a standardized test battery. Analyses included magnetic resonance imaging (N=2313) and neuropsychological (N=3001) samples. We used multivariable linear and logistic regression to relate AIVA to brain structural and neuropsychological functional measures.</p><p><strong>Results: </strong>The mean±SD age across participants was 62±11 years; 56% were women. In multivariable models, higher AIVA was associated with worse markers of cerebral small vessel disease (mean white matter free water: <i>β</i> [per SD], 0.09 [95% CI, 0.04-0.14]; <i>P</i><0.001; peak width of skeletonized mean diffusivity: <i>β</i>, 0.05 [95% CI, 0.00-0.10]; <i>P</i>=0.045; white matter hyperintensity volume: <i>β</i>, 0.08 [95% CI, 0.03-0.12]; <i>P</i><0.001) and higher odds of cerebrovascular injury (presence of extensive white matter hyperintensities: odds ratio [per SD], 1.22 [95% CI, 1.02-1.47]; <i>P</i>=0.03; presence of brain infarcts: odds ratio, 1.44 [95% CI, 1.02-2.04]; <i>P</i>=0.04). In addition, higher AIVA was associated with worse performance on Trails B-A (<i>β</i>, -0.05 [95% CI, -0.10 to -0.01]; <i>P</i>=0.03), similarities (<i>β</i>, -0.06 [95% CI, -0.11 to -0.01]; <i>P</i>=0.02), and global cognition (<i>β</i>, <i>-</i>0.07 [95% CI, -0.12 to -0.03]; <i>P</i>=0.002) and higher odds of prevalent depressive symptoms (odds ratio, 1.24 [95% CI, 1.08-1.41]; <i>P</i>=0.002) and high Center for Epidemiologic Studies Depression Scale score (odds ratio, 1.20 [95% CI, 1.00-1.44]; <i>P</i>=0.047). Vascular brain injury markers partially mediated the associations of AIVA with global cognition score and presence of depressive symptoms.</p><p><strong>Conclusions: </strong>Peripheral pressure waveform AIVA may be a novel, noninvasive indicator of subclinical vascular brain injury and neuropsychological function.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of Wearable Sleep Health Technology for Cardiovascular Health Assessment and Interventions: A Narrative Review.","authors":"Michael A Amadei, David A Reichenberger, Dorothy Tung, Hannah Gannon, Suzanne Gorovoy, Andrea Diaz-Pacheco, Michael A Grandner","doi":"10.1161/ATVBAHA.126.322875","DOIUrl":"10.1161/ATVBAHA.126.322875","url":null,"abstract":"<p><p>Sleep health is a multidimensional component of cardiovascular health, and modulating sleep as a cardiometabolic risk factor requires accurate measurement. Numerous technologies have emerged in the last 50 years to longitudinally characterize sleep over time in ambulatory settings, and their use by the public has grown. The impact of this democratization of health information through wearables has not been adequately explored in the literature. This narrative review equips clinicians and researchers with a mechanistic understanding of wearable sleep health technology to augment precision cardiovascular health assessment and intervention. Peer-reviewed literature was synthesized from PubMed, spanning foundational actigraphy studies through recent multisensor and electroencephalography-based device evaluations, with emphasis on device performance against polysomnography. Consistent with a narrative review, sources were selected through domain expertise rather than systematic screening. Wearable devices measure peripheral proxies to determine if the wearer is awake or asleep. The simplest method, actigraphy, uses motor activity to differentiate sleep from wake. Newer multisensor devices use actigraphy in addition to other physiological proxies of sleep (eg, heart rate, heart rate variability, skin temperature). Current device heterogeneity can diminish the validity of conclusions that can be drawn from wearable data; thus, performance evaluation against polysomnography is vital to determine the accuracy, sensitivity, and specificity of a device. Across evaluations, devices consistently show high sensitivity for detecting sleep but lower specificity for detecting wake; several consumer devices nonetheless perform comparably to research-grade actigraphy, some have received regulatory authorization for sleep apnea screening, and headband electroencephalography systems approach polysomnography-level staging. Wearable devices show promise as objective anchors to drive provider-patient interactions in cardiometabolic lifestyle interventions, offering scalable, valid measurement tools to quantify sleep health, and inform cardiovascular risk assessment. Interpretation requires awareness of structural device limitations, optimally through the understanding of the physiological concepts that underpin the function of these devices.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMPD1 Inhibition Attenuates Abdominal Aortic Aneurysm via Ceramide-Mediated NLRP3 Inflammatory Pathway.","authors":"Zhiwen Yang, Yifei Ruan, Yanbin Wang, Ke Liu, Yingxuan Li, Yihai Guo, Lu Qu, Yanting Tang, Xingqiao Chen, Linlu Peng, JiaJun Zhou, Xinzhong Li, Guojun Chen, Yulin Liao, Li Zhao, Jianping Bin, Yanmei Chen","doi":"10.1161/ATVBAHA.126.323961","DOIUrl":"https://doi.org/10.1161/ATVBAHA.126.323961","url":null,"abstract":"<p><strong>Background: </strong>Abdominal aortic aneurysm (AAA) is a lethal cardiovascular disease with high heritability but no effective pharmacotherapy. We aimed to identify and experimentally validate AAA-associated proteins with causal genetic support as therapeutic targets.</p><p><strong>Methods: </strong>We integrated large-scale AAA genome-wide association study and plasma proteomic data to identify causal proteins using Mendelian randomization, with validation in an independent cohort, colocalization, and multivariable Mendelian randomization single-cell RNA sequencing and cell isolation experiments identified the cellular source of SMPD1 (sphingomyelin phosphodiesterase 1) in AAA. Using recombinant SMPD1 and the inhibitor ASM-IN-1, we assessed the effects of SMPD1 in vitro on primary aortic endothelial cells and aortic smooth muscle cells and in vivo on AAA pathogenesis in PPE (porcine pancreatic elastase)-induced and angiotensin II-induced mouse models. We also assessed the role of ceramide (d18:1/16:0) in SMPD1‑driven AAA by measuring plasma ceramide levels, exogenous ceramide administration, and ASM‑IN‑1 rescue experiments. Therapeutic inhibition of SMPD1 with the Food and Drug Administration-approved drug amitriptyline was also assessed in vivo.</p><p><strong>Result: </strong>Mendelian randomization analysis identified 46 plasma proteins with causal genetic evidence for AAA, of which 6 (IL6R [interleukin-6 receptor], PCSK9 [proprotein convertase subtilisin/kexin type 9], NFKB1 [nuclear factor kappa B subunit], MMP1 [matrix metalloproteinase-1], TIMD4 [T-cell immunoglobulin and mucin domain-containing 4], and SMPD1) were validated. SMPD1 robustly colocalized with AAA susceptibility, an effect specifically mediated by ceramide (d18:1/16:0). SMPD1 was upregulated in AAA mice and originated from adventitial fibroblasts. Functional studies showed that SMPD1 promotes AAA by suppressing proliferation, inducing apoptosis/autophagy in endothelial cells and smooth muscle cells, amplifying inflammation, and promoting smooth muscle cell phenotypic switching. Moreover, SMPD1 drives AAA via the ceramide‑mediated NLRP3 inflammatory pathway. Pharmacological inhibition of SMPD1 with amitriptyline attenuated AAA progression.</p><p><strong>Conclusions: </strong>Integrated Mendelian randomization and experimental evidence identified SMPD1 as a novel AAA driver through the ceramide (d18:1/16:0)-mediated NLRP3 pathway, establishing SMPD1 as a promising therapeutic target.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipoprotein(a) and Incident Aortic Stenosis Over 30 Years: The ARIC Study.","authors":"Rafael Zubirán, Anna Wolska, Alan T Remaley","doi":"10.1161/ATVBAHA.126.325364","DOIUrl":"10.1161/ATVBAHA.126.325364","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Air Pollution Triggers Metabolomic Signature of Mitochondrial Dysfunction in Mice and Humans: Implications for Cardiovascular Disease Development.","authors":"Yan Lin, Xinghua Qiu, Rajat Gupta, Gajalakshmi Ramanathan, Xinchen Lu, Fen Yin, Oliver Fiehn, Junfeng Jim Zhang, Joel D Kaufman, Yifang Zhu, Michael Rosenfeld, Jesus A Araujo","doi":"10.1161/ATVBAHA.125.324277","DOIUrl":"10.1161/ATVBAHA.125.324277","url":null,"abstract":"<p><strong>Background: </strong>Previous animal studies found that subchronic exposure to diesel exhaust induces hyperlipidemia, accompanied by upregulation of 12-LOX (lipoxygenase) and 15-LOX pathways and hepatic mitochondrial dysfunction. However, the human relevance of these findings has not been established.</p><p><strong>Methods: </strong>We studied ApoE^-^/- mice exposed to diesel exhaust or filtered air for 2 weeks, and 26 healthy adults who traveled from Los Angeles (particulate matter with an aerodynamic diameter <2.5 µm: 14.4 µg/m³) to Beijing (particulate matter with an aerodynamic diameter <2.5 µM: 67.6 µg/m³) for 10 weeks. Both mice and humans were previously found to have increased 12- and 15-LOX metabolite levels but normal HDL (high-density lipoprotein) and total cholesterol levels in the blood after air pollution exposure. In this study, we profiled blood metabolomics and lipidomics across multiple platforms in mice and humans, and conducted integrated data analyses to identify common metabolic pathways that were affected by air pollution, mechanistically related to oxidative stress and hyperlipidemia.</p><p><strong>Results: </strong>Enrichment analysis of overlapping metabolites detected in both mice and humans indicates that air pollution induced metabolic alterations in (1) dicarboxylic acids, (2) acylcarnitines, (3) tryptophan, (4) pyrimidine, and (5) lysine pathways. Although the metabolomic signatures of tryptophan, pyrimidine, and lysine metabolites differed between mice and humans, we observed consistent increases in long-chain dicarboxylic acids and medium-to-long-chain acylcarnitines, likely due to mitochondrial dysfunction as evidenced by impaired mitochondrial respiration in a Seahorse assay on livers from the same mice. In the human study, the changes in dicarboxylic acids and acylcarnitines were significantly associated with increased lipid peroxidation products from 12- and 15-LOX pathways and exposure biomarkers for polycyclic aromatic hydrocarbons.</p><p><strong>Conclusions: </strong>We provide real-world human evidence supporting that mitochondrial dysfunction and impaired fatty acid oxidation are plausible mechanisms mediating the adverse early metabolic effects of air pollution.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary Alveolar Proteinosis: Rethinking Surfactant Homeostasis Through Alveolar Macrophage Lipid-Handling Dysfunction.","authors":"Elinor Lee, Isaiah J Little, Lucas Dantas, Elizabeth J Tarling","doi":"10.1161/ATVBAHA.126.322488","DOIUrl":"10.1161/ATVBAHA.126.322488","url":null,"abstract":"<p><p>Pulmonary alveolar proteinosis is a rare lung disease characterized by the accumulation of surfactant lipids and proteins within the alveolar space, leading to impaired gas exchange and progressive respiratory dysfunction. In most cases, pulmonary alveolar proteinosis arises from disruption of GM-CSF (granulocyte-macrophage colony-stimulating factor) signaling, resulting in defective alveolar macrophage maturation and a failure of surfactant clearance. Emerging work has reframed pulmonary alveolar proteinosis as a disorder of macrophage lipid handling, linking impaired cholesterol efflux and surfactant catabolism to both disease initiation and progression. In this review, we synthesize current understanding of pulmonary alveolar proteinosis pathophysiology, highlighting GM-CSF-dependent regulation of alveolar macrophage function, insights from animal and cellular models, and the evolving therapeutic landscape. We further discuss how targeting macrophage lipid homeostasis may offer new disease-modifying strategies.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}