Arteriosclerosis, Thrombosis, and Vascular Biology最新文献

{"title":"Potential Roles of SNX17, Rab11, and Rab5 in LDLR Recycling.","authors":"Xiaofei Zhao, Shiyin Long, Meiqi Zhu, Hong Hao, Ying Liao, Caiping Zhang, Zhenguo Liu","doi":"10.1161/ATVBAHA.125.322498","DOIUrl":"10.1161/ATVBAHA.125.322498","url":null,"abstract":"<p><p>Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality globally. Elevated levels of serum LDL-C (low-density lipoprotein cholesterol) represent a significant risk factor for atherosclerosis. LDLR (low-density lipoprotein receptor) plays a critical role in LDL-C uptake and clearance, with its recycling to the cell surface being essential for maintaining LDLR availability. However, the molecular mechanisms underlying LDLR homeostasis and recycling remain poorly defined. SNX (sorting nexin) proteins and Rab (Ras-associated binding protein) GTPases are key regulators of vesicle transport and endosomal sorting and are implicated in LDLR endocytosis, recycling, and subsequent cholesterol metabolism. This review aims to summarize the data on the roles of SNX17, Rab11, and Rab5 in LDLR recycling and endosomal dynamics, highlighting their potential as therapeutic targets for managing dyslipidemia and associated diseases.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e338-e354"},"PeriodicalIF":7.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324370","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":"Hepatic Inactivation of Carnitine Palmitoyltransferase 1a Lowers ApoB-Containing Lipoproteins in Mice.","authors":"Robert N Helsley, Mikala M Zelows, Victoria P Noffsinger, Garrett B Anspach, Nikitha Dharanipragada, Anna E Mead, Isidoro Cobo, Abigail Carter, Qinglin Wu, Irina Shalaurova, Kai Saito, Josh M Morganti, Scott M Gordon, Gregory A Graf","doi":"10.1161/ATVBAHA.125.322473","DOIUrl":"10.1161/ATVBAHA.125.322473","url":null,"abstract":"<p><strong>Background: </strong>Genome- and epigenome-wide association studies have associated variants and methylation status of CPT1a (carnitine palmitoyltransferase 1a) to reductions in VLDL (very low-density lipoprotein) cholesterol and triglyceride levels. The objective of this study was to determine the mechanisms by which CPT1a-dependent mitochondrial fatty acid oxidation influences hepatic and lipoprotein metabolism.</p><p><strong>Methods: </strong>Eight-week-old male and female <i>Cpt1a</i>-floxed mice (<i>Cpt1a</i>^fl/fl) and <i>Cpt1a</i>-floxed mice expressing the human apo B₁₀₀ transgene (<i>Cpt1a</i>^fl/fl/B100^Tg) were administered control adeno-associated virus or adeno-associated virus encoding Cre-recombinase under control of a liver-specific promoter (TBG-Cre [thyroxin-binding globulin]). Control and liver-specific knockout mice were placed on a low-fat control or western-type diet (42% kcal fat, 0.2% cholesterol) for 16 weeks. Livers were collected and used for histological and lipid analysis, while gene and protein expression were measured by bulk RNA-sequencing and immunoblotting, respectively. Lipoprotein composition in plasma was determined by size exclusion chromatography and nuclear magnetic resonance. Rates of VLDL-triglyceride secretion were quantified after lipase inhibition with poloxamer 407. Liquid and gas chromatography-mass spectrometry were used to measure bile acid species and fecal neutral sterols, respectively.</p><p><strong>Results: </strong>We report significant associations between the presence of <i>CPT1a</i> SNPs (single nucleotide polymorphisms) and reductions in plasma cholesterol, as well as positive associations between hepatic Cpt1a expression and plasma cholesterol levels across inbred mouse strains. Mechanistic studies show that both wild-type and human apo B₁₀₀ (apoB)-transgenic mice with liver-specific deletion of <i>Cpt1a</i> (liver-specific knockout) display lower circulating apoB levels consistent with reduced LDL (low-density lipoprotein)-cholesterol and LDL particle number. Despite a reduction in steady-state plasma lipids, VLDL-triglyceride and VLDL cholesterol secretion rates are increased, suggesting accelerated clearance of apoB-LPs (apoB-containing lipoproteins) in liver-specific knockout mice. Mechanistic approaches show greater PPARα (peroxisome proliferator-activated receptor α) signaling which favors enhanced lipoprotein lipase-mediated metabolism of apoB-LPs, including increases in apo AIV and apo CII and reductions in apo CIII and Angptl3 (angiopoietin-like 3).</p><p><strong>Conclusions: </strong>These studies provide mechanistic insight linking genetic variants and methylation status of <i>CPT1a</i> to reductions in circulating apoB-LPs in humans.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1368-1388"},"PeriodicalIF":7.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274117","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":"Change in Arterial Stiffness Is Associated With Change in Blood Glucose: Longitudinal Study in the Whitehall II Cohort.","authors":"Rachel E Climie, S Rehman, E J Brunner, P Boutouyrie, R M Bruno, J P Empana","doi":"10.1161/ATVBAHA.124.322001","DOIUrl":"10.1161/ATVBAHA.124.322001","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes is associated with elevated large artery stiffening, but arterial stiffening may also precede the development of type 2 diabetes. Whether the change in arterial stiffness over time is associated with dysglycemia across the entire spectrum of blood glucose concentration is unknown. Therefore, the primary objective of this study was to quantify the association between the change in arterial stiffness (exposure) and glycemic concentration (outcome).</p><p><strong>Methods: </strong>Within the prospective WHS II (Whitehall II Study), arterial stiffness was first measured in the 2007/09 examination round (baseline for the current study) and again in 2012/13, using the noninvasive, gold-standard method of carotid to femoral pulse wave velocity (cfPWV). Change in cfPWV was determined as cfPWV in 2012/13-cfPWV-cfPWV in 2007/09. Fasting blood glucose concentrations were measured at baseline (2007/09) and follow-up in 2012/13 and 2015/16.</p><p><strong>Results: </strong>There were 2632 participants without prior type 2 diabetes and cfPWV measured at 2 timepoints with follow-up in 2012/13 and 2282 with follow-up in 2015/16. Greater change in cfPWV was associated with significantly higher fasting glucose concentration at follow-up in 2012/13 and 2015/16 independently of confounders including cfPWV and fasting glucose levels at baseline (<i>P</i><0.001 for both). Greater change in cfPWV was significantly and independently associated with a greater change in fasting glucose concentration over the same period (2007/09-2012/13) and beyond (2007/09-2015/16).</p><p><strong>Conclusions: </strong>Minimizing premature arterial stiffening over time could be a valuable strategy for the prevention of glucose dysregulation and overt type 2 diabetes.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1459-1467"},"PeriodicalIF":7.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324366","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":"IL1β Secretion by Epididymal White Adipose Tissue Macrophages Regulates Myelopoiesis and Plaque Inflammation in Obese Mice and in Caloric Restriction.","authors":"Zhixing Li, Franziska Krautter, Maxwell La Forest, Edward A Fisher","doi":"10.1161/ATVBAHA.125.322789","DOIUrl":"10.1161/ATVBAHA.125.322789","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1468-1470"},"PeriodicalIF":7.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493819","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":"Novel Function for Endothelial Protease-Activated Receptors in Modulating Insulin Receptor Activity With Implications for Diabetes.","authors":"Rahul Rajala, Courtney T Griffin","doi":"10.1161/ATVBAHA.125.323140","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.323140","url":null,"abstract":"<p><strong>Background: </strong>Thrombin, a serine protease with increased activity in people with diabetes, signals through PAR (protease-activated receptor) 1 and 4 on endothelial cells (ECs). On these cells, PAR1 is a high-expressing, high-affinity, low-potency thrombin receptor, whereas PAR4 is a low-expressing, low-affinity, high-potency receptor. This study aims to determine how endothelial PARs influence diabetic pathology, thereby providing deeper insights into the roles and relationships between these receptors.</p><p><strong>Methods: </strong>We generated mice with inducible deletion of <i>Par1/Par4</i> in ECs (<i>Par1/4</i>^<i>iECko</i>) and induced diabetes with streptozotocin treatment. Blood glucose and insulin levels were assessed after streptozotocin administration. In addition, we measured insulin and glucose tolerance in <i>Par1/4</i>^<i>iECko</i> mice. Lastly, we measured how the loss of endothelial PARs in cultured primary ECs affected IR (insulin receptor) activity/phosphorylation, and insulin transcytosis.</p><p><strong>Results: </strong>Although studying the roles of endothelial PAR1/4 in diabetic pathology, we found that <i>Par1/4</i>^<i>iECko</i> mice displayed increased insulin sensitivity and were protected against streptozotocin-induced diabetes. Concordantly, we found that cultured primary ECs with PAR1/4 deficiency exhibited increased basal activity and phosphorylation of IR, as well as enhanced insulin transcytosis. This elevated IR activity correlated with reduced activity of PTP1B (protein tyrosine phosphatase 1B), a negative regulator of IR. Lastly, <i>Par1/4</i>^<i>iECko</i> mice with additional deletion of 1 allele of the endothelial IR gene demonstrated restoration of diabetic phenotypes after streptozotocin treatment, indicating that insulin sensitivity in <i>Par1/4</i>^<i>iECko</i> mice was driven by heightened IR activity in ECs.</p><p><strong>Conclusions: </strong>These findings establish a novel link between endothelial PAR signaling and IR regulation, underscoring the critical role of ECs in metabolic homeostasis and identifying a potential therapeutic target for diabetes.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752191","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":"Effective Transcriptional Induction of the CARMN/miR-143/145 Complex Locus in Smooth Muscle Cells Using CRISPR Activation.","authors":"Francesca Vacante, Sandra Sanchez-Esteban, Themistoklis Tsarouchas, Julie Rodor, Matthew Bennett, Melissa S Carroll, Abdelaziz Beqqali, Andrew H Baker","doi":"10.1161/ATVBAHA.124.322353","DOIUrl":"https://doi.org/10.1161/ATVBAHA.124.322353","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752159","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":"Role of Clot Formation and Plasminogen Activation in Lower Urinary Tract Pathologies.","authors":"Jonathan J Molina, Ana Lidia Flores-Mireles","doi":"10.1161/ATVBAHA.125.321600","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.321600","url":null,"abstract":"<p><p>Hemostasis, a critical physiological process, is essential for stopping bleeding and initiating tissue repair after injury. It involves a tightly coordinated interplay between coagulation (blood clotting) and fibrinolysis (clot breakdown). Dysregulation of hemostasis can result in a wide range of diseases, such as infections, cancers, metabolic disorders, and neurodegenerative disorders. In the urinary tract, disruption of homeostasis and induction of hemostasis by diseases or foreign bodies (such as urinary catheters) can lead to various problems, such as infections, inflammation, and structural damage. Furthermore, hemostatic proteins have been associated with severe cancer progression. Thus, highlighting the roles of clot formation and plasminogen activation in urinary tract pathologies is important. This review details the pathogenesis of the urinary tract and urothelial carcinoma, as well as the roles of clot formation and plasminogen activation during disease onset and progression.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752193","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":"Plasminogen Activation in Oral Mucosal Immunopathology.","authors":"Lina C Fellah, Lakmali M Silva","doi":"10.1161/ATVBAHA.125.322733","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.322733","url":null,"abstract":"<p><p>The Plg (plasminogen)/Pln (plasmin) system plays a broad range of roles in maintaining homeostasis at the oral mucosa, including homeostatic inflammation, tissue remodeling, and wound healing. Deregulation of these processes can lead to either increased or decreased proteolytic activity of Pln and, thereby, oral mucosal immunopathology. Here, we present a basic overview of the PAS (Plg activation system) components in the oral cavity and discuss how these factors are involved in oral mucosal homeostasis and disease pathogenesis. We reason that the role of the Plg/Pln system becomes evident in individuals with the Mendelian genetic defect, congenital Plg deficiency, who are predisposed to severe periodontitis in childhood due to defective fibrinolysis. Consistent with Plg deficiency as a risk factor for periodontitis, recent discovery of significant association between genetic polymorphisms in <i>PLG</i> and periodontal disease suggests <i>PLG</i> variants as candidate risk indicators for common forms of periodontitis.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752192","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":"Tricuspid Aortic Valve Regurgitation Associate With Ascending Aortic Aneurysm Through Endothelial Activation and Lipoprotein Infiltration.","authors":"David Freiholtz, Claudia Reyes-Goya, Karin Lång, Otto Bergman, Christian Olsson, Malin Granbom Koski, Michael Dismorr, Cecilia Österholm, Kenneth Caidahl, Anders Franco-Cereceda, Per Eriksson, Anton Gisterå, Hanna M Björck","doi":"10.1161/ATVBAHA.125.323112","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.323112","url":null,"abstract":"<p><strong>Background: </strong>An abnormal accumulation of immune cells and inflammation has been described in ascending aortic aneurysm, but the factor driving disease initiation remains elusive. Interestingly, ascending aortic dilatation often occurs alongside aortic regurgitation but rarely with aortic stenosis. We sought to investigate ascending aortic aneurysm initiation by assessing the relation between aortic regurgitation and vascular activation and inflammation.</p><p><strong>Methods: </strong>In this prospective cohort study, patients with tricuspid aortic valves undergoing elective open-heart surgery were included. Aortic specimens from organ donors were obtained through the University of Miami Tissue Bank. Spatial transcriptomics measured gene expression in nondilated aortic endothelium, intima, and subintima. Immunohistochemistry determined protein expression. Aortic dimensions were recorded preoperatively and 10 years after surgery using echocardiography. Aortic gene expression affected by physiological blood flow was previously measured in Wistar rats.</p><p><strong>Results: </strong>We show a mesenchymal activation of endothelial cells, possibly mediated by bidirectional flow, in the nondilated ascending aorta of patients with aortic valve regurgitation, accompanied by intimal infiltration, retention, and oxidation of apoB-containing lipoproteins. We further observed intimal upregulation of genes coding for core proteins of lipoprotein-binding proteoglycans and the <i>OLR1</i>, the latter by infiltrating macrophages and in association with progressive inflammation and dilatation. None of the above was observed in patients with aortic stenosis. Notably, surgical replacement of regurgitant valves, but not stenotic valves, mitigated 10-year aortic growth.</p><p><strong>Conclusions: </strong>Our results highlight a distinct pathological role of aortic valve regurgitation in ascending aortic aneurysm formation by promoting mesenchymal activation of endothelial cells and lipoprotein-related immune cell infiltration and inflammation in patients with tricuspid aortic valves. We also provide novel insights into the long-term impact of surgical aortic valve replacement on ascending aortic growth and suggest a diagnostic or therapeutic target in oxidized low-density lipoprotein cholesterol.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752194","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":"Neutrophil Integrin α9 Impairs Efferocytosis and Worsens Long-Term Recovery After Subarachnoid Hemorrhage.","authors":"Harpreet Kaur, Nilesh Pandey, Lakshmi Chandaluri, Nirvana Shaaban, Dhananjay Kumar, Rajan Pandit, Alexa Martinez, Sumit Kumar Anand, Sandeep Das, Sumati Rohilla, Fabio Arias, Erika Reece, Ravinder Reddy Gaddam, Kevin S Murnane, Ajit Vikram, Rajesh Mohandas, Xiaolu Zhang, Mohammad Alfrad Nobel Bhuiyan, Xiao-Hong Lu, A Wayne Orr, Oren Rom, Arif Yurdagul, Nirav Dhanesha","doi":"10.1161/ATVBAHA.125.323072","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.323072","url":null,"abstract":"<p><strong>Background: </strong>Neutrophil infiltration exacerbates brain injury after subarachnoid hemorrhage (SAH). Integrin α9, expressed on neutrophils, facilitates their adhesion and transendothelial migration, leading to aggravated inflammatory responses and neuronal apoptosis. Insufficient clearance of apoptotic neurons by microglia and infiltrating blood-derived macrophages (defective efferocytosis) contributes to persistent inflammation and poor SAH recovery. This study investigated the role of neutrophil integrin α9 in neuronal apoptosis, microglia/macrophage efferocytosis, and SAH outcomes.</p><p><strong>Methods: </strong>Neutrophil-specific <i>α9</i>^<i>-/-</i> (<i>α9</i>^<i>fl/fl</i><i>Mrp8Cre</i>^<i>-/+</i>) and littermate control (<i>α9</i>^<i>fl/fl</i><i>Mrp8Cre</i>^<i>-/-</i>) mice were subjected to the endovascular perforation model to induce SAH. Sensorimotor and cognitive function were assessed for up to 4 weeks post-SAH using neurological severity score, corner and cylinder tests, Y-maze, and novel object recognition. In vitro and in vivo functional assays were conducted to assess the effect of integrin α9-dependent neutrophil transendothelial migration on efferocytosis of apoptotic neurons. Neutrophil infiltration, cerebral inflammation, neuronal apoptosis, and MMP (matrix metalloproteinase)-9 were quantified 24 hours post-SAH.</p><p><strong>Results: </strong>Mice subjected to SAH exhibited increased integrin α9 levels on infiltrated neutrophils compared with sham surgery controls. Neutrophil-specific <i>α9</i>^<i>-/-</i> mice demonstrated improved long-term sensorimotor and cognitive recovery, reduced neutrophil infiltration, and decreased MMP-9 expression and neuronal apoptosis. Importantly, neutrophil-specific <i>α9</i>^<i>-/-</i> mice exhibited reduced brain neutrophil elastase levels and enhanced efferocytosis. Mechanistic studies have revealed that the reduced transendothelial migration of <i>α9</i>^<i>-/-</i> neutrophils directly contributed to the enhanced microglia/macrophage efferocytosis of apoptotic neurons. Pharmacological targeting of integrin α9 with macitentan significantly improved SAH outcomes by reducing neutrophil infiltration and enhancing efferocytosis. Comparable SAH outcomes in both macitentan-treated controls and neutrophil-specific <i>α9</i>^<i>-/-</i> mice suggested that the therapeutic effects of macitentan were mediated by inhibition of neutrophil integrin α9.</p><p><strong>Conclusions: </strong>Our study revealed a novel role for neutrophil integrin α9 in sensorimotor function and cognitive recovery after SAH, suggesting it as a potential therapeutic target for SAH.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752190","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}