Arteriosclerosis, Thrombosis, and Vascular Biology最新文献

{"title":"Association of Serum Thromboinflammatory Biomarkers With Atherosclerotic Plaques and Burden in a Community-Based Population.","authors":"Baoshan Qiu, Xueli Cai, Lebo Zhou, Xuan Wang, Shan Li, Nan Wang, Lingling Jiang, Jing Jing, Tiemin Wei, Yongjun Wang, Yuesong Pan, Yilong Wang","doi":"10.1161/ATVBAHA.125.322586","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.322586","url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis of atherosclerosis involves complex mechanisms, with inflammation playing a central role. Thromboinflammation may contribute to its development and progression. We investigated the association between circulating thromboinflammatory biomarkers and atherosclerotic plaques.</p><p><strong>Methods: </strong>Participants aged 50 to 75 years from the baseline survey of the PRECISE study (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) were included. Serum levels of thromboinflammatory biomarkers (sGPVI [soluble glycoprotein VI]; sADAMTS13 [soluble a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13]; and sP-selectin) were assessed by ELISA and Luminex assays and categorized into quartiles based on their empirical distribution within the study population. Eligible participants underwent imaging using computed tomography angiography and magnetic resonance imaging for coronary atherosclerosis, intracranial atherosclerosis, and extracranial atherosclerosis, respectively.</p><p><strong>Results: </strong>A total of 3019 participants (mean age, 61.20±6.68 years; 46.47% male) were analyzed. After multivariable adjustment, participants in the fourth quartile of sGPVI levels had higher odds of coronary atherosclerotic plaque burden (common odds ratio, 1.42 [95% CI, 1.14-1.76]; <i>P</i>=0.0017). Conversely, those in the highest sADAMTS13 quartile had lower odds of coronary plaques (odds ratio, 0.75 [95% CI, 0.60-0.93]; <i>P</i>=0.0094), as well as reduced coronary plaque burden, including segment involvement score (common odds ratio, 0.75 [95% CI, 0.61-0.93]; <i>P</i>=0.0087) and segment stenosis score (common odds ratio, 0.75 [95% CI, 0.61-0.93]; <i>P</i>=0.0086). No significant associations were observed between sGPVI or sADAMTS13 levels and intracranial or extracranial atherosclerosis. Likewise, after multivariable adjustment, no significant associations were observed between sP-selectin levels and coronary, intracranial, or extracranial atherosclerosis.</p><p><strong>Conclusions: </strong>In our study, serum sADAMTS13 levels showed a negative association with both the presence and burden of coronary atherosclerosis, while sGPVI levels showed a positive association with the burden of coronary atherosclerosis. However, significant associations between the level of thromboinflammatory biomarkers, intracranial atherosclerosis, and extracranial atherosclerosis were not found.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551795","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":"LDL-Bound PCSK9 Has a Slower Clearance Kinetic and Higher Use for HSPGs Than Free-PCSK9.","authors":"Silvia Cecilia Pacheco-Velázquez, Carlota Oleaga, Bastian Ramms, Joshua Hay, Paul A Mueller, Ester López-Aguilar, Joshua Miles, Ryan N Porell, Chelsea Nora, Kamil Godula, Hagai Tavori, Philip L S M Gordts, Sergio Fazio, Nathalie Pamir","doi":"10.1161/ATVBAHA.124.322334","DOIUrl":"https://doi.org/10.1161/ATVBAHA.124.322334","url":null,"abstract":"<p><strong>Background: </strong>Hepatic heparan sulfate proteoglycans (HSPGs) accelerate the clearance of PCSK9 (proprotein convertase subtilisin/kexin type 9). We tested the hypothesis that free- and LDL (low-density lipoprotein)-bound PCSK9 forms have different HSPG-mediated clearance kinetics.</p><p><strong>Methods: </strong>Metabolic and turnover studies were performed after administration of free- and LDL-bound PCSK9 to 2 HSPG knockout mouse models: (1) Global knockout of syndecan-1 (<i>Sdc1</i>^-/^-), an HSPG involved in hepatic triglyceride clearance; and (2) hepatocyte-specific knockout of heparan sulfate N-deacetylase/N-sulfotransferase <i>(AlbCre</i>^<i>+</i><i>Ndst1</i>^<i>f/f</i>).</p><p><strong>Results: </strong>The clearance of both free- and LDL-bound PCSK9 followed a 2-phase decay behavior comprising a fast and a slow phase. The more notorious effect of HSPG deletion was on the slow phase: the clearance of free-PCSK9 was faster in <i>Sdc1</i>^<i>-/</i>^<i>-</i> mice (t_1/2,slow 13.5±1.5 minutes; <i>P</i>=0.0305) than in wild-type (t_1/2,slow 28.8±4.2 minutes) and <i>AlbCre</i>^<i>+</i><i>Ndst1</i>^<i>f/f</i> mice (t_1/2,slow 32.7±4.9 minutes). The clearance of LDL-bound PCSK9 was slower yet not statistically significant in <i>Sdc1</i>^<i>-/</i>^<i>-</i> mice (t_1/2,slow 111.2±21.6 minutes) than in wild-type (t_1/2,slow 52±6.4 minutes) and <i>AlbCre</i>^<i>+</i><i>Ndst1</i>^<i>f/f</i> mice (t_1/2,slow 39.55±2.96 minutes). However, the area under the curve showed a delayed clearance of LDL-bound PCSK9 in <i>Sdc1</i>^<i>-/</i>^<i>-</i> mice (44 576±2435 min×ng, <i>P</i>=0.004) but not in <i>AlbCre</i>^<i>+</i><i>Ndst1</i>^<i>f/f</i> (34 738±3721 min×ng, <i>P</i>=0.578) mice compared with wild-type (30 865±1907 min×ng). Hepatic <i>Ndst1</i>-deficiency did not alter hepatic PCSK9 or LDLR (LDL receptor) expression.</p><p><strong>Conclusions: </strong>The clearance rate of plasma LDL-bound PCSK9 is slower than the clearance rate of its free form. The HSPG syndecan-1 modestly contributes to PCSK9 clearance through an LDLR-independent pathway.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551797","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":"METTL3 Exacerbates Intimal Hyperplasia by Facilitating m⁶A-YTHDC1-Dependent SGK1 Gene Transcription.","authors":"Jiaqi Huang, Qianqian Feng, Zhigang Dong, Zhuofan Li, Yihan Liu, Ran Xu, Zhujiang Liu, Qianhui Ding, Xueyuan Yang, Fang Yu, Yiting Jia, Yuan Zhou, Wei Kong, Hao Tang, Yi Fu","doi":"10.1161/ATVBAHA.125.322961","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.322961","url":null,"abstract":"<p><strong>Background: </strong>Vascular smooth muscle cell (VSMC) migration and proliferation substantially contribute to neointimal hyperplasia related to in-stent restenosis. N⁶-methyladenosine (m⁶A) modification catalyzed by the METTL3 (methyltransferase-like 3)-containing methyltransferase complex is the most abundant RNA epigenetic modification in eukaryotes, but the role of m⁶A RNA methylation in VSMC migration and proliferation and neointima formation remains highly controversial.</p><p><strong>Methods: </strong>Primary human and rat VSMCs were utilized for in vitro experiments. VSMC-specific METTL3 knockout mice (<i>Mettl3</i>^flox/flox<i>Myh11</i>-CreER^T2) were generated to explore the role of METTL3 in carotid artery wire injury in vivo. Methylated RNA immunoprecipitation sequencing was performed to screen for genes targeted for METTL3-catalyzed m⁶A RNA methylation. Methylation site mapping, methylated RNA immunoprecipitation-quantitative polymerase chain reaction, chromatin immunoprecipitation-quantitative polymerase chain reaction, and reporter gene assays were used to explore how METTL3 modulates target gene expression.</p><p><strong>Results: </strong>METTL3 expression was consistently upregulated in the neointima of mice subjected to carotid wire injury and in those of patients who underwent carotid endarterectomy. VSMC-specific METTL3 deficiency significantly attenuated neointima formation in mouse carotid arteries after wire injury. Accordingly, METTL3 ablation markedly repressed VSMC proliferation both in vitro and in vivo. Mechanistically, METTL3 directly catalyzed the m⁶A methylation of SGK1 (serum/glucocorticoid-regulated kinase 1) mRNA and subsequently facilitated its transcription, a process that was dependent on the established association between the SGK1 transcript and SGK1 promoter DNA via recruitment of the m⁶A reader YTHDC1 (YT521-B homology domain-containing protein 1). Conversely, SGK1 overexpression abolished the METTL3 deficiency-mediated suppression of VSMC proliferation and postinjury neointima formation.</p><p><strong>Conclusions: </strong>METTL3-catalyzed m⁶A RNA methylation promoted VSMC proliferation and exacerbated postinjury neointima formation by facilitating YTHDC1-dependent SGK1 gene transcription. Targeting the METTL3-YTHDC1-SGK1 axis to modulate VSMC proliferation may be a potential strategy for in-stent restenosis therapy.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551817","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":"Endothelium- and Fibroblast-Derived C-Type Natriuretic Peptide Prevents the Development and Progression of Aortic Aneurysm.","authors":"Aisah A Aubdool, Amie J Moyes, Cristina Perez-Ternero, Reshma S Baliga, Jaspinder Singh Sanghera, M Taaha Syed, Kareemah Jaigirdar, Anmolpreet K Panesar, Janice C Tsui, Yanming Li, Hernan G Vasquez, Ying H Shen, Scott A LeMaire, Juliette Raffort, Ziad Mallat, Hong S Lu, Alan Daugherty, Adrian J Hobbs","doi":"10.1161/ATVBAHA.124.322350","DOIUrl":"10.1161/ATVBAHA.124.322350","url":null,"abstract":"<p><strong>Background: </strong>Thoracic (TAA) and abdominal (AAA) aortic aneurysm are life-threatening diseases characterized by dilation, inflammation, and structural weakness; development of pharmacological therapies is desperately needed. CNP (C-type natriuretic peptide) plays a key role in vascular homeostasis, mediating vasodilator, anti-inflammatory, and antiatherogenic actions. Since such processes drive AA, we determined the role of endogenous CNP in offsetting pathogenesis.</p><p><strong>Methods: </strong>Tissue from patients with AA was analyzed to determine the consequences on CNP signaling. Ascending and suprarenal aortic diameters were assessed at baseline and following Ang II (angiotensin II; 1.44 mg/kg per day) infusion in wild-type, endothelium-restricted (ecCNP^-/-), fibroblast-restricted (fbCNP^-/-), global CNP (gbCNP^-/-), or global NPR-C^-/- mice infected with an adeno-associated virus expressing a proprotein convertase subtilisin/kexin type 9 gain-of-function mutation or backcrossed to an apoE^-/- background. At 28 days, aortas were harvested for RT-qPCR (quantitative reverse transcription polymerase chain reaction) and histological analyses. CNP (0.2 mg/kg per day) was infused to rescue any adverse phenotype.</p><p><strong>Results: </strong>Aneurysmal tissue from patients with TAA and AAA revealed that CNP and NPR-C (natriuretic peptide receptor-C) expression were overtly perturbed. ecCNP^-/-, fbCNP^-/-, and gbCNP^-/- mice exhibited an aggravated phenotype compared to wild-type animals in both ascending and suprarenal aortas, exemplified by greater dilation, fibrosis, elastin degradation, and macrophage infiltration. CNP and NPR-C expression was also dysregulated in murine thoracic AA and abdominal AA, accompanied by increased accumulation of mRNA encoding markers of inflammation, extracellular matrix remodeling/calcification, fibrosis, and apoptosis. CNP also prevented activation of isolated macrophages and vascular smooth muscle cells. An essentially identical phenotype was observed in NPR-C^-/- mice and while administration of CNP protected against disease severity in wild-type animals, this phenotypic rescue was not apparent in NPR-C^-/- mice.</p><p><strong>Conclusions: </strong>Endothelium- and fibroblast-derived CNP, via NPR-C activation, plays important roles in attenuating AA formation by preserving aortic structure and function. Therapeutic strategies aimed at mimicking CNP bioactivity hold potential to reduce the need for surgical intervention.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1044-1063"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771220","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":"Platelet-Derived PDGF-A Disrupts Blood-Brain Barrier Integrity in Ischemic Stroke-Brief Report.","authors":"Vanessa Göb, Lena Zimmermann, Katherina Hemmen, Axel Haarmann, Katrin G Heinze, Michael K Schuhmann, David Stegner","doi":"10.1161/ATVBAHA.125.321191","DOIUrl":"10.1161/ATVBAHA.125.321191","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke (IS) is a prevalent cause of death and disability worldwide. Cerebral ischemia induces profound changes at the blood-brain barrier, which lead to a remarkable increase in paracellular permeability, worsening outcomes. Platelets are well known for safeguarding vascular integrity and the prevention of bleeding complications. On the other hand, platelet activation contributes to infarct progression in the context of IS. The manifold, context-dependent roles of platelets, however, have not yet been resolved.</p><p><strong>Methods: </strong>IS was mimicked by transient middle cerebral artery occlusion in wild-type, transgenic, or treated mice, and vascular leakage was assessed by intravital 2-photon microscopy, as well as Western blotting and immunohistochemistry. Barrier property of primary murine brain microvascular endothelial cells was measured as transendothelial electrical resistance of cellular monolayers in response to platelet releasate or recombinant proteins.</p><p><strong>Results: </strong>IS induces blood-brain barrier breakdown characterized by time-dependent leakage of albumin in the brain parenchyma. We could show that local platelet activation triggers the release of PDGF (platelet-derived growth factor)-A from α-granules, which induces the loss of brain endothelial cell layer integrity. This translates to a comprised vascular integrity in vivo. In the absence of α-granule content (<i>Nbeal2</i>^<i>-/-</i>) or pharmacological blockade of PDGF, no disruption of the endothelial layer or vascular leakage was observed.</p><p><strong>Conclusions: </strong>PDGF-A released from platelets impairs blood-brain barrier integrity, resulting in detrimental vascular leakage and infarct progression. These findings provide important insights on the pivotal role of platelets in IS further elucidating the mechanisms of thrombo-inflammation in the brain.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1166-1174"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075597","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":"Afadin Promotes Vascular Smooth Muscle Cell Contraction by Interacting With Phospholipase C to Enhance Ca²⁺ Signaling for Blood Pressure Regulation.","authors":"Md Mahbubur Rahman Khan, Akira Sato, Akio Shimizu, Shunji Suetaka, Md Rasel Molla, Masahiro Komeno, Mst Zenika Nasrin, Masanari Nishida, Futoshi Toyoda, Munehito Arai, Hisakazu Ogita","doi":"10.1161/ATVBAHA.125.322619","DOIUrl":"10.1161/ATVBAHA.125.322619","url":null,"abstract":"<p><strong>Background: </strong>Vascular smooth muscle cells (VSMCs) regulate vascular tone and blood pressure. Stimulation of VSMCs with vasoconstrictors, such as AngII (angiotensin II) or norepinephrine, activates the G-protein-coupled receptor-mediated cascade, leading to a hypercontractile state and vascular remodeling. Afadin, an intracellular adaptor protein that mainly localizes at cell-cell junctions, regulates various biological phenomena. However, its role in VSMCs remains unclear.</p><p><strong>Methods: </strong>VSMCs were isolated from newly generated VSMC-specific afadin conditional knockout mice. A small peptide (7 amino acids) designed in silico to inhibit the afadin-PLC (phospholipase C) β association was administered to the mouse VSMCs and aortic media using adeno-associated virus.</p><p><strong>Results: </strong>Unlike control mice, afadin conditional knockout mice did not exhibit AngII- or norepinephrine-induced elevation in blood pressure. VSMCs isolated from afadin conditional knockout mice were less responsive to AngII- or norepinephrine-induced cell contractility compared with control VSMCs, as evidenced by reduced release of intracellular Ca²⁺ resulting from lowered production of AngII- or norepinephrine-induced inositol 1,4,5-trisphosphate. Mechanistically, the PDZ (disk large tumor suppressor, zonula occludens-1) domain of afadin was shown to associate with the C terminus of PLCβ, providing support for the localization of PLCβ on the plasma membrane, where it generates inositol 1,4,5-trisphosphate. Furthermore, the newly designed small peptide, which inhibited the afadin-PLCβ association, attenuated AngII-induced cell contractility and intracellular Ca²⁺ release in vitro and blocked AngII-stimulated blood pressure elevation in vivo.</p><p><strong>Conclusions: </strong>Afadin expression in VSMCs promotes cell contraction by interacting with PLCβ to enhance Ca²⁺ signaling and has potential as a novel molecular target for blood pressure regulation.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1226-1243"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172547","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":"Nitrosation of CD36 Regulates Endothelial Function and Serum Lipids.","authors":"Melissa A Luse, Wyatt J Schug, Luke S Dunaway, Shruthi Nyshadham, Skylar A Loeb, Alicia Carvalho, Rachel Tessema, Caitlin Pavelec, T C Stevenson Keller, Xiaohong Shu, Claire A Ruddiman, Anna Kosmach, Timothy M Sveeggen, Ray Mitchell, Pooneh Bagher, Richard D Minshall, Norbert Leitnger, Linda Columbus, Kandice R Levental, Ilya Levental, Miriam Cortese-Krott, Brant E Isakson","doi":"10.1161/ATVBAHA.124.321964","DOIUrl":"10.1161/ATVBAHA.124.321964","url":null,"abstract":"<p><strong>Background: </strong>During obesity, endothelial cells (ECs) become lipid laden, leading to endothelial dysfunction. We tested posttranslational modification on cluster of differentiation 36 (CD36) that may regulate EC lipid accumulation.</p><p><strong>Methods: </strong>We used an EC-specific Cav1 (caveolin-1) knockout mouse, nitrosation and palmitoylation assays, and whole animal Nγ-nitro-l-arginine methyl ester administration to examine blood lipids.</p><p><strong>Results: </strong>EC-specific Cav1 knockout male mice are hyperlipidemic regardless of diet but retain endothelial cell function. We found these mice have significantly increased NO in response to the lack of Cav1, and the presence or absence of NO toggled inversely EC lipid content and plasma lipid in mice. The NO nitrosated the fatty acid translocase CD36 at the same cysteines that are palmitoylated on CD36. The nitrosation of CD36 prevented its trafficking to the plasma membrane and decreased lipid accumulation. The physiological effect of this mechanism was a reliance on NO for endothelial function and not dilation.</p><p><strong>Conclusions: </strong>This work suggests that CD36 nitrosation occurs as a protective mechanism to prevent EC lipotoxicity.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"1067-1086"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966202","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":"Correction to: C-X-C Ligand 16 Is an Independent Predictor of Cardiovascular Death and Morbidity in Acute Coronary Syndromes.","authors":"Thomas Andersen, Thor Ueland, Tatevik Ghukasyan Lakic, Axel Åkerblom, Maria Bertilsson, Pål Aukrust, Annika E Michelsen, Stefan K James, Richard C Becker, Robert F Storey, Lars Wallentin, Agneta Siegbahn, Frederic Kontny","doi":"10.1161/ATV.0000000000000187","DOIUrl":"https://doi.org/10.1161/ATV.0000000000000187","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":"45 7","pages":"e336"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493822","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":"C-Type Natriuretic Peptide: Protecting the Aorta.","authors":"S Jeson Sangaralingham, John C Burnett","doi":"10.1161/ATVBAHA.125.322802","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.322802","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":"45 7","pages":"1064-1066"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493823","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":"Elevated Plasma MBL Levels Are Associated With Risk of Future Venous Thromboembolism: The HUNT Study.","authors":"Christabel Esi Damoah, Solveig M Valderhaug, Omri Snir, Kristian Dalsbø Hindberg, Sigrid K Brækkan, Steven P Grover, Therese H Nøst, Péter Gál, Gábor Pál, Christian Jonasson, Peter Garred, Tom Eirik Mollnes, Kristian Hveem, John-Bjarne Hansen","doi":"10.1161/ATVBAHA.124.322052","DOIUrl":"10.1161/ATVBAHA.124.322052","url":null,"abstract":"<p><strong>Background: </strong>MBL (mannose-binding lectin), a pattern recognition molecule circulating in complex with MASPs (MBL-associated serine proteases), activates the lectin complement pathway and facilitates thrombin generation upon binding to specific moieties on pathogens or altered host cells. We aimed to investigate the association between plasma MBL levels and risk of future venous thromboembolism (VTE) and to explore the effect of MBL-MASP-1/2 complexes on thrombin generation.</p><p><strong>Methods: </strong>We conducted a population-based case-cohort (294 VTE patients, 1066 sex- and age-weighted subcohorts) derived from HUNT (The Trøndelag Health Study). Plasma MBL levels were measured using the SomaScan 7k aptamer-based platform. Cox proportional hazards regression models were used to estimate hazard ratios for VTE across quartiles of MBL levels. Thrombin generation in plasma induced by MBL-MASPs complexes was assessed in vitro.</p><p><strong>Results: </strong>Subjects with MBL levels in the highest quartile had a 79% higher risk of overall VTE (hazard ratio, 1.79 [95% CI, 1.23-2.61]) than those with MBL levels in the lowest quartile after multivariable adjustments. The risk estimates by high plasma MBL were particularly strong for deep vein thrombosis (hazard ratio, 2.50 [95% CI, 1.42-4.37]) and unprovoked VTE (hazard ratio, 2.81 [95% CI, 1.53-5.16]). MBL-MASP-1/2 complexes promoted complement activation and thrombin generation, and monospecific inhibitors abolished their enzymatic activity.</p><p><strong>Conclusions: </strong>Our findings support the notion that high plasma MBL levels are associated with an increased risk of future VTE and suggest that the risk increase is partially mediated through the initiation of thrombin generation by MBL-MASP-1/2 complexes at the site of venous thrombosis formation.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324-e335"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075592","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}