Arteriosclerosis, Thrombosis, and Vascular Biology最新文献

{"title":"Sex-Specific Risk of Smoking for Abdominal Aortic Aneurysm and Exploration of Potential Mechanism: Meta-Analysis and Prospective Cohort Study.","authors":"Paul Welsh, Anna Louise Pouncey, Naveed Sattar, Janet T Powell","doi":"10.1161/ATVBAHA.125.322601","DOIUrl":"10.1161/ATVBAHA.125.322601","url":null,"abstract":"<p><strong>Background: </strong>Smoking is the strongest modifiable risk factor for the development of abdominal aortic aneurysm (AAA). This study aims to confirm whether smoking is a stronger risk factor in women than men and identify contributory reasons, including inflammation, for any sex-specific difference observed.</p><p><strong>Methods: </strong>Systematic review and meta-analysis, conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. Data sources were Medline, Embase, and Cochrane Central Register of Controlled Trials. Population-based studies reporting the risk of AAA, adjusted for age and cardiovascular risk factors, for women versus men, were included. These were complemented by data from UK Biobank, which also were assessed for sex-specific effects of smoking on incident atherosclerotic cardiovascular disease.</p><p><strong>Results: </strong>Meta-analysis of 6 studies (including UK Biobank, 2001-2024) showed that the relative risk ratio of current versus never smokers for incident AAA in women versus men was 1.78 (95% CI, 1.32-2.38). In the UK Biobank cohort, the sex-specific relative risks of current smoking risks were higher for AAA than for atherosclerotic cardiovascular disease; hazard ratio, 1.74 and 1.29, respectively: analysis by cigarettes per day echoed these findings, but pack-year history had lesser association. The proportionately lower AAA incidence rate in exsmokers (versus current smokers) was more marked in women. Sex-specific risks of current smoking for incident AAA were not significantly modified by CRP (C-reactive protein), white blood cell count, or other inflammatory markers.</p><p><strong>Conclusions: </strong>The relative risk of developing AAA by current smokers is almost twice as high in women versus men, but no strong association with inflammation was observed. Other reasons, including smoking intensity, must be sought.</p><p><strong>Registration: </strong>URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD2024586609.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1316-1325"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952832","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":"Real-World Effectiveness and Safety of Evinacumab in Children and Adults With Homozygous Familial Hypercholesterolemia: A Multisite US Perspective-Brief Report.","authors":"Michael J Wilkinson, Priyesha Bijlani, Michael H Davidson, P Barton Duell, Mary Horan, Mary J Malloy, Ron S Newfield, Pallavi Pradeep, Prediman K Shah, Eveline O Stock, Bruce A Warden, Matthew K Ito","doi":"10.1161/ATVBAHA.124.322364","DOIUrl":"10.1161/ATVBAHA.124.322364","url":null,"abstract":"<p><strong>Background: </strong>Homozygous familial hypercholesterolemia (HoFH) is an autosomal semidominant disorder characterized by extreme elevations in LDL-C (low-density lipoprotein cholesterol) and early-onset atherosclerotic cardiovascular disease. Evinacumab is a monoclonal antibody administered by monthly intravenous infusion that binds ANGPTL3 (angiopoietin-like 3) and when added to standard lipid-lowering therapies lowers LDL-C by ≈50% in HoFH clinical trials. Studies examining the real-world effectiveness and safety of evinacumab are limited.</p><p><strong>Methods: </strong>We performed a retrospective study to assess the effectiveness and safety of evinacumab in patients with HoFH in clinical practice at 6 US academic medical centers. The primary end point was the percent change in LDL-C from baseline to first follow-up and to the most recent follow-up after evinacumab initiation. Secondary end points were percent change in non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, total cholesterol, HDL-C, and achievement of an LDL-C <70 mg/dL. Adverse events were recorded.</p><p><strong>Results: </strong>Twenty-four patients (mean age, 40 [range, 5-84] years) with HoFH were followed for a median of 48 weeks. Fifty percent were female, 66.7% had atherosclerotic cardiovascular disease, 87.5% were on a statin, 83.3% were on ezetimibe, 66.7% were on PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitors), 24% were on lomitapide, and 33.3% were undergoing lipoprotein apheresis. Significant reductions in LDL-C, non-HDL-C, total cholesterol, triglycerides, and HDL-C were observed both at the first follow-up (4 weeks) and the most recent follow-up (48 weeks); mean±SEM percent change from baseline to the most recent follow-up was as follows: LDL-C, -53.2% (±4.1); non-HDL-C, -52.7% (±3.9); triglycerides, -47.4% (±5.1); total cholesterol, -48.9% (±4.0); and HDL-C, -30.2% (±4.1); <i>P</i><0.001 for all. Significantly more patients achieved LDL-C <70 mg/dL after evinacumab was added. Nine (37.5%) patients reported adverse events during or following evinacumab infusions. Treatment was discontinued by 1 patient because of back pain.</p><p><strong>Conclusions: </strong>Across 6 US academic medical centers, evinacumab was generally well tolerated by patients with HoFH and lowered LDL-C by ≈50%, consistent with results from clinical trials.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1310-1315"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172566","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":"Just Say NO to CD36 Expression: A Regulatory Pathway With Implications in Many Chronic Diseases.","authors":"Roy L Silverstein","doi":"10.1161/ATVBAHA.125.322894","DOIUrl":"10.1161/ATVBAHA.125.322894","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1087-1089"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224169","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":"Single-Cell Transcriptomics and Lineage Tracing Unveil Parallels in Lymphatic Muscle and Venous Smooth Muscle Development, Identity, and Function.","authors":"Guillermo Arroyo-Ataz, Alejandra Carrasco Yagüe, Julia C Breda, Sarah A Mazzilli, Dennis Jones","doi":"10.1161/ATVBAHA.125.322567","DOIUrl":"10.1161/ATVBAHA.125.322567","url":null,"abstract":"<p><strong>Background: </strong>Lymphatic muscle cells (LMCs) are indispensable for lymphatic vessel contraction, and their aberrant recruitment or absence is associated with both primary and secondary lymphedema. Despite their critical role in lymphatic vessel function, the cellular and molecular bases that confer the unique contractile properties to LMCs are largely undefined, limiting the development of therapeutic interventions that precisely target LMCs.</p><p><strong>Methods: </strong>We used single-cell RNA sequencing, genetic lineage tracing, whole mount immunostaining, and intravital imaging to investigate the basis for the hybrid cardiomyocyte and blood vascular smooth muscle cell (SMC) characteristics that have been described for LMCs.</p><p><strong>Results: </strong>Using single-cell RNA sequencing, the transcriptomes of LMCs and venous SMCs exhibited more similarities than differences, with both cell types exhibiting enrichment in overlapping molecular markers. Notably, LMCs and venous SMCs were both markedly distinct from that of arteriole SMCs. Functionally, both lymphatic vessels and blood vessels in the murine hind limb displayed pulsatile contractility, and their functions were regulated by gabapentin and nifedipine, which target the activity of voltage-gated calcium channels. Although LMCs express genes that overlap with the venous SMC transcriptome, lineage tracing demonstrates that LMCs do not originate from Myh11 (myosin heavy chain 11) lineage-derived SMCs, Nkx2.5 (NK2 homeobox 5) cardiomyocyte progenitors, or Wnt1 (Wnt family member 1) neural crest progenitors. Instead, most LMCs and SMCs in the hind limb and inguinal-axillary region originate from WT1⁺ (Wilms tumor gene 1) mesodermal progenitors from the lateral plate mesoderm. LMCs derived from WT1⁺ progenitors were critical for the maintenance of lymphatic vessel contractility.</p><p><strong>Conclusions: </strong>Overall, our findings suggest that venous SMCs and LMCs derive from a related mesodermal progenitor and acquire a similar gene expression program that facilitates their contractile properties.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1207-1225"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075611","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":"Visualizing Vascular Bone Marrow Niche Alterations in Diabetes.","authors":"Narmeen Haj, Ashish Tiwari, Maria Berihu, Nedaa Kher, Siraj Nsraldeen, Maya Holdengreber, Shiri Karni-Ashkenazi, Bin Zhou, Galit Saar, Daniel J Stuckey, Katrien Vandoorne","doi":"10.1161/ATVBAHA.124.322358","DOIUrl":"10.1161/ATVBAHA.124.322358","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is characterized by chronic hyperglycemia that leads to systemic vascular complications. Hyperglycemia impairs endothelial function and promotes vascular inflammation, resulting in leukocytosis, altered hematopoiesis, and cardiovascular complications. Bone marrow endothelial cells play a pivotal role in regulating myeloid progenitor cells and leukocyte trafficking. However, the effects of diabetes on the structure and function of bone marrow vasculature remain poorly understood. To address this, we used a multiscale imaging approach integrating intravital microscopy, dynamic contrast-enhanced magnetic resonance imaging, and multispectral optoacoustic tomography to investigate diabetes-induced vascular changes in the bone marrow.</p><p><strong>Methods: </strong>Diabetes was induced in C57BL/6J female mice using streptozotocin. Flow cytometry and histology characterized bone marrow myeloid progenitors, blood leukocytes, and bone marrow endothelial cell populations, as well as hypoxia. Intravital microscopy was used to visualize vascular density, permeability, and sprouting angiogenesis in the calvarial marrow. Dynamic contrast-enhanced magnetic resonance imaging quantified vascular density and permeability in the femoral marrow, while multispectral optoacoustic tomography assessed hemoglobin oxygenation in the calvarial marrow.</p><p><strong>Results: </strong>Hyperglycemia significantly increased myelopoiesis, leading to elevated leukocytosis driving diabetic inflammation. Flow cytometry and histology revealed increased bone marrow endothelial cell numbers (<i>P</i>=0.0006), while intravital microscopy showed elevated vascular permeability (<i>P</i>=0.0095) and sprouting angiogenesis (<i>P</i>=0.0095). Dynamic contrast-enhanced magnetic resonance imaging confirmed greater vascular density (<i>P</i>=0.019) and leakiness (<i>P</i>=0.0062), and multispectral optoacoustic tomography detected reduced hemoglobin oxygenation and increased hypoxia in the diabetic marrow (<i>P</i>=0.0065), reflecting a hypoxic niche favorable to hematopoietic stem and progenitor cells. This likely drives angiogenesis and contributes to inflammatory hematopoiesis in diabetes.</p><p><strong>Conclusions: </strong>This study demonstrates that diabetes induces profound vascular remodeling and hypoxia in the bone marrow, reshaping the hematopoietic niche and driving myelopoiesis and leukocytosis. By validating dynamic contrast-enhanced magnetic resonance imaging and multispectral optoacoustic tomography as noninvasive translational tools, coupled with intravital microscopy, we provide a comprehensive framework for exploring novel therapies targeting bone marrow vasculature to mitigate inflammation-driven outcomes in diabetes.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1192-1206"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224170","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":"Clonal Hematopoiesis of Indeterminate Potential Is Associated With Incident Abdominal Aortic Aneurysm.","authors":"Yu Tan, Xuanmeng Zhu, Yuanfeng Huang, Chenxuan Zhao, Xunjie Cheng, Jinchen Li, Guogang Zhang, Tianqi Ma, Shujun Yang, Yongping Bai","doi":"10.1161/ATVBAHA.124.322630","DOIUrl":"10.1161/ATVBAHA.124.322630","url":null,"abstract":"<p><strong>Background: </strong>Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging risk factor for cardiovascular diseases. Genetic IL (interleukin)-6 signaling deficiency reduced cardiovascular disease risk in CHIP carriers. However, the association between CHIP and incident abdominal aortic aneurysm (AAA) and whether IL-6 signaling inhibition attenuates AAA risk among individuals with CHIP remained unclear.</p><p><strong>Methods: </strong>Participants without prevalent AAA from the UK Biobank were included. The associations of any CHIP (variant allele fraction, ≥2%), large CHIP (variant allele fraction, ≥10%), and gene-specific CHIP subtypes with incident AAA were investigated. The protection role of <i>IL6R</i> p.Asp358Ala, a genetic proxy for IL-6 deficiency, was tested after stratification by CHIP status. Furthermore, the interaction and joint effects of CHIP and genetic susceptibility on AAA risk were tested.</p><p><strong>Results: </strong>This study included 425 211 participants. Any CHIP and large CHIP was identified in 13 768 (3.2%) and 8576 (2.0%) participants, respectively. CHIP was associated with an increased risk of incident AAA (hazard ratio [HR], 1.21 [95% CI, 1.01-1.44]; <i>P</i>=0.034), with large CHIP clones exhibiting greater effect size (HR, 1.35 [95% CI, 1.10-1.66]; <i>P</i>=0.0045). Driver gene-specific analyses revealed that <i>ASXL1</i>-mediated CHIP exerted the strongest effect size on AAA risk (HR, 2.10 [95% CI, 1.54-2.88]; <i>P</i><0.001). The presence of 2 <i>IL6R</i> p.Asp358Ala alleles attenuated the risk of AAA in large CHIP carriers (HR, 0.48 [95% CI, 0.23-0.99]; <i>P</i>=0.046). In the joint analysis, participants with CHIP and high genetic risk had a higher risk of developing AAA than those without CHIP and with low genetic risk (HR, 2.15 [95% CI, 1.63-2.85]; <i>P</i><0.001).</p><p><strong>Conclusions: </strong>CHIP is associated with an increased risk of AAA. Genetic IL-6 signaling deficiency attenuates the risk of AAA in large CHIP carriers. CHIP may serve as an attractive target for the prevention and treatment of AAA.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1326-1336"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967218","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":"Discovery of σ₂R/TMEM97 as a Novel Biomarker for Atherosclerotic Plaques: A PET Imaging and Validation Study.","authors":"Tiantian Mou, Jingqi Wang, Biao Hu, Mingxin Gao, Mingkai Yun, Xu Gao, Yi Tian, Haiyang Li, Hongmei Jia, Xiaoli Zhang, Yiyun Huang","doi":"10.1161/ATVBAHA.125.322721","DOIUrl":"10.1161/ATVBAHA.125.322721","url":null,"abstract":"<p><strong>Background: </strong>The aims of this study were to evaluate σ₂R (sigma-2 receptor)/TMEM97 (transmembrane protein 97) expression in atherosclerotic plaques, and assess the feasibility of in vivo atherosclerotic plaques imaging using the σ₂R/TMEM97 targeting probe 1-(4-(5,6-dimethoxyisoindolin-2-yl)butyl)-3-(2-[¹⁸F]fluoroethyl)-1,3-dihydro-2<i>H</i>-benzo[<i>d</i>]imidazol-2-one ([¹⁸F]SYB-NF) developed in our laboratory.</p><p><strong>Methods: </strong>Hematoxylin and eosin and immunohistochemical staining were performed on both human coronary endarterectomy specimens and mouse samples. The expression of σ₂R/TMEM97 in RAW 264.7 cells incubated with ox-LDL (oxidized low-density lipoprotein) was analyzed using western blot analysis. Positron emission tomography imaging with [¹⁸F]SYB-NF, [¹⁸F]NaF, and 2-[¹⁸F]fluoro-2-deoxy-d-glucose was conducted in wide-type C57BL/6 and ApoE^-/- mice. Specific binding was evaluated by coinjecting [¹⁸F]SYB-NF with the σ₂R/TMEM97 antagonist CM398 ([1-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1<i>H</i>)-yl)butyl)-3-methyl-1<i>H</i>-benzo[<i>d</i>]imidazol-2(3<i>H</i>)-one]). Autoradiography and Oil Red O staining were performed on harvested aortas and corresponding sections.</p><p><strong>Results: </strong>Staining results demonstrated significant upregulatiaon of σ₂R/TMEM97 expression at the early plaque formation and throughout the atherosclerosis progression. Western blot analysis indicated that incubation of macrophages with ox-LDL led to increased σ₂R/TMEM97 expression. [¹⁸F]SYB-NF specifically accumulated in the aortic arch of ApoE^-^/- mice. Treatment with CM398 significantly reduced the standardized uptake value in the aortic arch of ApoE^-^/- mice. [¹⁸F]SYB-NF exhibited a higher standardized uptake value in the aortic arch (0.67±0.09 versus 0.51±0.07) and higher aortic arch-to-heart ratio (2.58 versus 0.56) in ApoE^-^/- mice compared with 2-[¹⁸F]fluoro-2-deoxy-d-glucose, and a higher aortic arch-to-bone ratio (2.24 versus 0.44) compared with [¹⁸F]NaF. Autoradiography analysis revealed a strong correlation between the positive area in Oil Red O staining and autoradiography (Pearson correlation coefficient=0.993; <i>P</i>=0.001), further supporting the association between elevated σ₂R/TMEM97 expression and plaque formation.</p><p><strong>Conclusions: </strong>σ₂R/TMEM97 may serve as a potential biomarker for atherosclerotic plaques, and σ₂R/TMEM97 positron emission tomography imaging may be used to monitor plaque formation and progression, as well as the efficacy of emerging therapeutic strategies for atherosclerotic plaques.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1111-1123"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118638","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":"Super-Enhancer-Driven LncRNA UNC5B-AS1 Inhibits Inflammatory Phenotypic Transition in Pulmonary Artery Smooth Muscle Cells via Lactylation.","authors":"Xiangrui Zhu, Xiangming Pang, Xiaoying Wang, Xiaoyu Guan, Yujing Tang, Zhaosi Wang, Lixin Zhang, Xiaodong Zheng, Fei Li, Jian Mei, Langlin Ou, Yuxiang Liu, Zitong Meng, Yingli Chen, Cui Ma","doi":"10.1161/ATVBAHA.124.322174","DOIUrl":"10.1161/ATVBAHA.124.322174","url":null,"abstract":"<p><strong>Background: </strong>The phenotypic transition of pulmonary artery smooth muscle cells (PASMCs) is a central pathological alteration in pulmonary artery remodeling, contributing to pulmonary hypertension. Super-enhancers (SEs), characterized by histone modifications and the binding of coactivators, drive the expression of prominent genes that define cellular identity. However, the specific role of SEs, particularly SE-driven lncRNAs (long noncoding RNAs), in hypoxia-induced phenotypic plasticity of PASMCs remains unclear.</p><p><strong>Methods: </strong>In this study, the lncRNA UNC5B antisense RNA 1 (UNC5B-AS1) regulated by SEs was screened in hypoxic PASMCs using RNA sequencing and H3K27ac (histone 3 lysine 27 acetylation) ChIP (chromatin immunoprecipitation) sequencing. Overexpression or knockdown of UNC5B-AS1 in vitro was performed to elucidate its role in pulmonary hypertension pathogenesis. A serotype 5 adenovirus-associated virus carrying a conserved functional fragment of UNC5B-AS1 was used to treat pulmonary hypertension in vivo.</p><p><strong>Results: </strong>We identified UNC5B-AS1 as an SE-driven lncRNA transcriptionally activated by the transcription factor FOXP3 (forkhead box protein P3), which regulates phenotypic transition in PASMCs. Notably, we demonstrated that UNC5B-AS1 interacts with key glycolytic enzymes in the cytoplasm and likely serves as a molecular scaffold for LRPPRC (leucine-rich PPR motif-containing protein) and oxidative respiratory chain complex IV in mitochondria. Consequently, the deficiency of UNC5B-AS1 in PASMCs promotes the lactylation of promoter regions within inflammatory genes, including those of IL (interleukin)-1β, IL-6, and TNF-α (tumor necrosis factor-α), under hypoxic conditions, ultimately leading to inflammatory phenotypic transition of PASMCs.</p><p><strong>Conclusions: </strong>Our findings identify SE-driven UNC5B-AS1 as a novel regulatory factor in the hypoxia-induced phenotypic transition of PASMCs and suggest that overexpression of UNC5B-AS1 may represent a promising therapeutic strategy for pulmonary hypertension.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e307-e323"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972245","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":"ADAMTS-13 Prevents VWF-Mediated Gastric Cancer Metastasis.","authors":"Chen-Yu Wang, Min Wang, Chan-Yuan Zhao, Quan Zhou, Xiao-Yu Zhang, Feng-Xia Wang, Jia-Ming Dong, Cun-Pu Du, Chen-Li Zhang, Yun Dang, Ai-Jun Yang, Jing-Fei Dong, Min Li","doi":"10.1161/ATVBAHA.125.322553","DOIUrl":"10.1161/ATVBAHA.125.322553","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer invades local tissue extensively and metastasizes through the circulation to remote organs. Patients with metastasized gastric cancer have poor clinical outcomes. The vasculature in the cancer niche is developed poorly, thus allowing cancer cells to be released into the circulation. However, it is poorly understood how cancer cells adhere to and transmigrate through the fully developed endothelium in remote organs and what key adhesive ligands are involved in the process. Here, we report results from a study designed to investigate the role of hyperadhesive VWF (von Willebrand factor) in promoting the pulmonary metastasis of gastric cancer.</p><p><strong>Methods: </strong>We used mouse models to investigate the roles of hyperadhesive VWF in the pulmonary metastasis of gastric cancer. The findings from these mouse models were validated through in vitro experiments that specifically examined how VWF promoted gastric cancer-derived extracellular vesicles to activate endothelial cells and analyzed established databases of patients with gastric cancer.</p><p><strong>Results: </strong>VWF in cancer-bearing mice became hyperadhesive and mediated the adhesion of gastric cancer-derived extracellular vesicles to the endothelium, where gastric cancer-derived extracellular vesicles caused endothelial permeability and promoted the transmigration of cancer cells to the interstitial tissue of the lungs. Reducing VWF adhesive activity by the metalloprotease ADAMTS-13 (A disintegrin and metalloprotease with thrombospondin type motifs, type 13) prevented the pulmonary metastasis of gastric cancer cells in mice. We further validated the findings in mice through targeted in vitro experiments and by associating VWF with the outcomes of patients with gastric cancer through established databases of patients with gastric cancer using bioinformatics tools.</p><p><strong>Conclusions: </strong>We show how VWF becomes hyperadhesive to promote the pulmonary metastasis of gastric cancer through its interaction with gastric cancer-derived extracellular vesicles and that the hyperadhesive activity of VWF is reduced by ADAMTS-13 to prevent the metastasis.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e271-e285"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961510","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":"Metabolic Regulation of Vascular Smooth Muscle Potassium Channels by Perivascular Adipose Tissue.","authors":"Maik Gollasch, Mario Kassmann, Daniele Teixeira Alves, Ulrike Garscha, Dmitry Tsvetkov","doi":"10.1161/ATVBAHA.125.321693","DOIUrl":"10.1161/ATVBAHA.125.321693","url":null,"abstract":"<p><p>This brief review describes recent advances in understanding metabolic control of vascular smooth muscle cells, highlighting the identification of KCNQ5 (K_V7.5 subfamily of voltage-gated K⁺ channels) as a crucial component. KCNQ5 has been found to play a key role in enabling the convergence of input signals from the perivascular adipose tissue, which include numerous oxylipins. These findings are significant because they shed light on the mechanisms by which vascular smooth muscle cells regulate vascular tone and blood pressure. By focusing on the interaction between KCNQ5 and perivascular adipose tissue, research has uncovered a complex pathway that allows for the modulation of vascular responses through a variety of lipid-derived signaling molecules. This discovery not only provides deeper insight into the cellular processes affecting vascular function but also opens up potential new avenues for therapeutic interventions in vascular diseases. The identification of KCNQ5 as a pivotal mediator in these processes is a critical step forward in cardiovascular research, offering new perspectives on how vascular health can be maintained and how various diseases might be targeted more effectively.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1031-1040"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118639","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}