Arteriosclerosis, Thrombosis, and Vascular Biology最新文献

{"title":"Circulating IgM Antibody Levels Against Oxidation-Specific Epitopes and Their Association With Age-Related Macular Degeneration.","authors":"Azin Kheirkhah, Maria Ozsvar-Kozma, Claudia Lamina, Klaus J Stark, Taras Afonyushkin, Martina E Zimmermann, Caroline Brandl, Iris M Heid, Florian Kronenberg, Christoph J Binder","doi":"10.1161/ATVBAHA.126.324949","DOIUrl":"10.1161/ATVBAHA.126.324949","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease (CVD) is associated with age-related macular degeneration (AMD), suggesting shared pathogenic pathways. Natural IgM antibodies targeting oxidation-specific epitopes (OSEs) are well characterized in CVD and may contribute to AMD. To date, no observational study has assessed the association between OSE-IgM and AMD, including among individuals with concomitant CVD. Here, we investigate this relationship in large population-based cross-sectional data of old-aged individuals.</p><p><strong>Methods: </strong>We measured IgM antibodies against phosphocholine-modified bovine serum albumin (PC), malondialdehyde-modified low-density lipoprotein (MDA-LDL), and copper-oxidized low-density lipoprotein (CuOx-LDL) in up to 2264 participants with and without AMD of the AugUR study (Age-Related Diseases: Understanding Genetic and Nongenetic Influences-a Study at the University of Regensburg; 627 cases, 1637 controls; age, 70-95 years). Antibody levels were inverse-normalized, and multinomial mixed regression analyses were performed to evaluate their associations with different AMD stages.</p><p><strong>Results: </strong>Women exhibited significantly higher levels of all 3 OSE-IgM compared with men. Elevated levels of IgM against PC were associated with 12% decreased odds (odds ratio, 0.88 [95% CI, 0.80-0.97]; <i>P</i>=0.01) for any AMD. When we investigated OSE-IgM associations with different stages of AMD (early AMD, late AMD), we found that all 3 OSE-IgM were associated with ≈20% lower odds for late AMD, but none with early AMD. Associations of OSE-IgM with late AMD were stronger in men than in women. Of the participants, 490 individuals had documented CVD. A significant interaction was observed between levels of PC IgM and CVD status in their associations with early AMD (<i>P</i>=0.049). In a subset of participants with CVD, PC IgM levels were associated with 34% decreased odds (odds ratio, 0.66 [95% CI, 0.51-0.86]; <i>P</i>=0.002) for early AMD.</p><p><strong>Conclusions: </strong>This study identifies an inverse association between IgM antibodies targeting PC, MDA-LDL, and CuOx-LDL and late AMD, but not with early AMD. However, in the early stage of AMD, an association with PC IgM is only observed when the participants had documented CVD. These findings may suggest a possible protective role of OSE-IgM antibodies in AMD pathogenesis and progression.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324949"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618266","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":"Δ⁹-THC Promotes Profibrotic Cell States In Vitro and Impairs Vascular Function In Vivo.","authors":"Nerea Jimenez-Tellez, Francesca Vacante, Themistoklis M Tsarouchas, Cody Juguilon, Alberto Casas-Ortiz, Mark Chandy, Tzu-Tang Wei, Joseph C Wu","doi":"10.1161/ATVBAHA.125.324193","DOIUrl":"10.1161/ATVBAHA.125.324193","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324193"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676607","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":"Innate Immune Memory Responses in Organ Transplantation.","authors":"Lisanne C de Jong, Nils Rother, Raphaël Duivenvoorden","doi":"10.1161/ATVBAHA.125.323925","DOIUrl":"10.1161/ATVBAHA.125.323925","url":null,"abstract":"<p><p>Innate immunity is a critical contributor to graft rejection and cardiovascular complications after organ transplantation, with increasing evidence indicating that innate immune memory significantly influences graft outcomes. The most extensively studied form, trained immunity, involves epigenetic and metabolic reprogramming of innate immune cells, altering their inflammatory responsiveness. Numerous transplantation-related factors, including metabolic disturbances such as hypercholesterolemia and hyperglycemia, can induce trained immunity, and both experimental and clinical studies have linked it to graft survival. Although trained immunity reflects responses to nonspecific stimuli, innate allogeneic memory shows that innate immune cells can recognize nonself and mount donor-specific memory responses. This review covers the current knowledge on both forms of innate immune memory in the context of solid organ transplantation.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e323925"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454376","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":"Systematic Review and Meta-Analysis Examining the Effect of Upregulation and Inhibition of Proprotein Convertase Subtilisin/Kexin Type 9 in Mouse Models of Abdominal Aortic Aneurysm.","authors":"Callan D Wesley, Shivshankar Thanigaimani, Abid Khan, Jonathan Golledge","doi":"10.1161/ATVBAHA.126.324982","DOIUrl":"10.1161/ATVBAHA.126.324982","url":null,"abstract":"<p><strong>Background: </strong>Abdominal aortic aneurysm (AAA) rupture is an important cause of death worldwide, with no effective drug therapies currently available. PCSK9 (proprotein convertase subtilisin/kexin type 9) regulates LDL-C (low-density lipoprotein-cholesterol) and modulates vascular inflammation, smooth muscle cell apoptosis, and extracellular matrix remodeling, all implicated in AAA pathogenesis.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis of studies evaluating the effects of PCSK9 upregulation or inhibition on AAA in mouse models. The primary outcome was AAA diameter, with secondary outcomes including lipid and inflammatory markers. Five articles (11 studies, 101 experimental, and 84 control mice) were included. Meta-analysis results were reported as standardized mean difference and 95% CIs. A custom tool, which integrated Cochrane criteria, ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines, and methods from prior systematic reviews, was used to assess the risk of bias.</p><p><strong>Results: </strong>PCSK9 upregulation significantly increased AAA diameter (standardized mean difference, 1.07 [95% CI, 0.33-1.81]; <i>P</i>=0.005) and blood concentrations of total cholesterol, LDL (low-density lipoprotein), and triglycerides while significantly reducing blood concentrations of high-density lipoprotein. PCSK9 upregulation also increased aortic IL (interleukin)-6 and IL1-β concentrations, as assessed by aortic immunohistochemical staining. PCSK9 inhibition significantly reduced AAA diameter (standardized mean difference, -0.97 [95% CI, -1.44 to -0.49]; <i>P</i><0.0001) and blood concentrations of IL-1β, IL-6, and TNF-α (tumor necrosis factor-alpha). Risk of bias was low-to-moderate across studies.</p><p><strong>Conclusions: </strong>In mouse models, PCSK9 upregulation promoted larger AAAs, while PCSK9 inhibition promoted smaller AAAs. These effects were associated with changes in lipid and inflammatory markers. PCSK9 inhibition may be a target to limit AAA growth.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324982"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366822","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":"Vascular Health and Gender-Affirming Hormone Therapy: The Immune System in Motion.","authors":"Jeimison D Santos, Jefferson Elias-Oliveira, Ualter G Cipriano, Pedro Vargas-Pinilla, Daniela Carlos, Vania L D Bonato, Rita C Tostes","doi":"10.1161/ATVBAHA.125.322093","DOIUrl":"10.1161/ATVBAHA.125.322093","url":null,"abstract":"<p><p>Given that fluctuations in sex hormone levels greatly influence cardiovascular homeostasis, this review addresses how gender-affirming hormone therapy impacts vascular function and the immune system, and how these effects may contribute to altered cardiovascular performance in transgender individuals. Gender-affirming hormone therapy alters leukocyte activation and cytokine secretion, that may impact vascular responsiveness, with distinct effects in feminizing and masculinizing regimens. Moreover, gender-affirming hormone therapy-induced changes in the gut microbiome and body composition, together with factors such as sex chromosomes, and environmental stressors may further modulate inflammatory states with potential consequences for cardiovascular health. This review also discusses factors that limit current research, contributing to inconsistent findings and persistent gaps in understanding the cardiovascular and immunologic effects of gender-affirming hormone therapy, along with directions for future studies. Although available data remain limited, understanding these interconnections is essential for optimizing therapeutic strategies, improving cardiovascular health, and fostering more inclusive clinical practices for the transgender community.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e322093"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410183","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":"Olfactomedin 2 Promotes Atherosclerosis by Eliciting Smooth Muscle Foam Cell Formation.","authors":"Ning Shi, Dunpeng Cai, Bysani Chandrasekar, Yusuke Higashi, Shi-You Chen","doi":"10.1161/ATVBAHA.125.323448","DOIUrl":"10.1161/ATVBAHA.125.323448","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis is a chronic vascular disease with a complex pathophysiology involving smooth muscle cell (SMC) dysfunction, and Olfm2 (olfactomedin 2) plays a role in SMC phenotype modulation. However, it is unclear if Olfm2 is involved in the development of atherosclerosis.</p><p><strong>Methods: </strong>Olfm2 global and SMC-specific knockout models were used to study its role in the development of atherosclerosis.</p><p><strong>Results: </strong>We found that Olfm2 was upregulated in atherosclerotic plaques of high-fat diet-fed ApoE^-/- (apolipoprotein E) mice in vivo and in oxLDL (oxidized low-density lipoprotein)-treated SMCs in vitro, suggesting the involvement of Olfm2 in SMC foam cell formation (SFCF). Indeed, knockdown of Olfm2 inhibited, while overexpression of Olfm2 promoted oxLDL-induced SFCF. Moreover, lipid accumulation and atherosclerotic lesion areas were significantly reduced in the aortas of high-fat diet-fed Olfm2^-/- ApoE^-/- mice compared with those in ApoE^-/- mice, demonstrating that Olfm2 is a novel regulator promoting atherosclerosis. Mechanistically, Olfm2 physically interacted with IκBα (inhibitor of nuclear factor κB) and facilitated the release of NF-κB (nuclear factor κB) from the NF-κB/IκBα complex, leading to activation of NF-κB signaling, which, in turn, promoted SFCF and subsequent atherosclerosis development. Olfm2 functions in atherosclerosis and SFCF were further confirmed by using an inducible SMC-specific Olfm2-deficient mouse model.</p><p><strong>Conclusions: </strong>Olfm2 is a novel regulator that promotes SFCF and atherosclerosis by activating NF-κB signaling. Targeting Olfm2 may be a novel potential therapeutic strategy against atherosclerosis.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e323448"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454374","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":"Vascular Endothelial Growth Factor Receptors 1 and 3 Mediate Placental Trophoblast Leptin Production in Preeclampsia, Inducing Vascular Dysfunction.","authors":"Mona Elgazzaz, Safia Ogbi, Desmond Moronge, Elisabeth Mellott, Gibson Cooper, Kristin Backer, Amalia Brawley, Gabrielle Hernendez, Joanna Hitchings, Luis Valesquez Zarate, Sravankumar Kavuri, Tae Jin Lee, Daria V Ilatovskaya, Padmashree C Woodham, James Maher, Brian H Annex, Jessica L Faulkner","doi":"10.1161/ATVBAHA.125.324143","DOIUrl":"10.1161/ATVBAHA.125.324143","url":null,"abstract":"<p><strong>Background: </strong>Heightened sFlt-1 (soluble FMS-like tyrosine kinase-1) level is a hallmark of preeclampsia patients and induces a state of angiogenic imbalance by sequestering free VEGF (vascular endothelial growth factor) and PlGF (placental growth factor). The receptors for VEGF and PlGF, membrane-bound VEGFR (VEGF receptor), are expressed in placental trophoblast cells, but their functions in this cell type are largely unknown. Placental production of leptin significantly increases in preeclampsia, and we recently showed that leptin induces placental and vascular endothelial dysfunction in pregnancy. We hypothesized that inappropriately high sFlt-1 in preeclampsia leads to an increase in trophoblast leptin production.</p><p><strong>Methods: </strong>We treated human placental explants, trophoblast, and adipose cells with sFlt-1. We also infused pregnant mice with sFlt-1 via osmotic minipump from mid-late gestation.</p><p><strong>Results: </strong>We show an increase in leptin peptide production, which is ablated by coadministration with either VEGF or PlGF (placental growth factor). We further demonstrate that VEGFR1 and 3, not R2, expressions are predominant in human trophoblasts and that reducing activation of these receptors mediates trophoblast leptin production. In pregnant mice, we show that sFlt-1 infusion induces vascular endothelial dysfunction in association with significantly elevated plasma leptin levels. In pregnant sFlt-1-infused mice, treatment with a leptin receptor antagonist significantly ablated vascular endothelial dysfunction.</p><p><strong>Conclusions: </strong>Collectively, these data indicate that angiogenic imbalance in preeclampsia impacts placental trophoblast endocrine function by suppressing VEGFR1 and 3 activation, resulting in leptin overproduction. Furthermore, sFlt-1 induces vascular endothelial dysfunction in mice dependent on leptin receptor activation.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324143"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13353211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410180","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":"Hypoxia-Inducible Factor Prolyl Hydroxylase EGLN3 Stabilizes Atherosclerotic Plaques in <i>ApoE</i>^-/- Mice Independently of Its Catalytic Activity.","authors":"Ying Jin, Lei Xu, Yulian Xiong, Dejiao Sun, Lanlan Liu, Xiaodong Lu, Ye Yuan, Nan Yang, Ziyi Ren, Dezhi Lu, Yao Liu, Fei Zheng, Yamu Pan, Lin Tian, Jian Fu","doi":"10.1161/ATVBAHA.125.323765","DOIUrl":"10.1161/ATVBAHA.125.323765","url":null,"abstract":"<p><strong>Background: </strong>The NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat-containing receptor family pyrin domain-containing 3) inflammasome plays a causal role in driving atherosclerosis. HIF (hypoxia-inducible factor) prolyl hydroxylase EGLN3 (<i>Caenorhabditis elegans</i> gene egl-9 [EGLN] 3) inhibits NFκB (nuclear factor kappa B) signaling independently of its hydroxylase activity. This study determined the role and mechanism of EGLN3 prolyl hydroxylase in regulating NLRP3 inflammasome activation, vascular inflammation, and the development of atherosclerosis.</p><p><strong>Methods: </strong><i>ApoE</i>^-/- (apolipoprotein E) mice deficient for global EGLN3, macrophage EGLN3, or EGLN3 hydroxylase activity were used to explore the role of EGLN3 and its activity in atherosclerosis. MCC950 was applied to antagonize the NLRP3 inflammasome in mice. Various cellular and molecular methods were used for mechanistic studies.</p><p><strong>Results: </strong>EGLN3 elimination promotes the production of mitochondrial reactive oxygen species and the release of mitochondrial DNA in macrophages. EGLN3 ablation enhances NLRP3 inflammasome assembly and promotes GSDMD (gasdermin D) cleavage, IL (interleukin) 1β production, and pyroptosis of macrophages. TRAF6 (TNF receptor-associated factor 6) catalyzes lysine (K) 63-linked NLRP3 ubiquitination and potentiates NLRP3 inflammasome assembly and activation, which can be antagonized by EGLN3. EGLN3 also blunts K63-polyubiquitination of TRAF6. EGLN3 deficiency enhances lipid uptake through increasing CD36 expression and impedes cholesterol efflux by declining ABCA1 (ATP-binding cassette transporter A1) expression, thereby boosting macrophage foam cell formation. EGLN3 depletion restrains MerTK (c-mer tyrosine kinase) expression and efferocytosis of macrophages. Inhibition of the NLRP3 inflammasome counteracts the impacts of EGLN3 deficiency on foam cell formation and efferocytosis. Global and macrophage-specific ablation of EGLN3 exacerbates vascular inflammation and instability of the atherosclerotic plaques in <i>ApoE</i>^-/- mice. Pharmacological inhibition of the NLRP3 inflammasome ameliorates the detrimental effect of EGLN3 deficiency on vascular inflammation and the formation and stability of the plaques. Genetic inactivation of EGLN3 activity retains its ability to restrict NLRP3 inflammasome activation and atherosclerosis development.</p><p><strong>Conclusions: </strong>EGLN3 inhibits NLRP3 inflammasome assembly and activation through antagonizing TRAF6-induced NLRP3 ubiquitination and activation. EGLN3 suppresses vascular inflammation and atherosclerosis by modulating pyroptosis, foam cell formation, and efferocytosis of macrophages through targeting the NLRP3 inflammasome. EGLN3 protects against atherosclerosis independently of its hydroxylase activity.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e323765"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410062","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":"miR487a-3p and miR6855-3p Facilitate Macrophage Proinflammatory Polarization and Lipid Accumulation in Atherosclerosis.","authors":"Haijing Ge, Duo Xu, Tao He, Zixing Zhang, Weina Wang, Jing Wan, Huanhuan Cai, Hairong Wang, Sumanth D Prabhu, Zhibing Lu, Qiongxin Wang","doi":"10.1161/ATVBAHA.126.325069","DOIUrl":"10.1161/ATVBAHA.126.325069","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The integrated regulation of microRNAs on macrophage plasticity plays a key role in atherosclerosis. We tested the hypothesis that miR487a-3p and miR6855-3p accelerate atherosclerosis by intensifying macrophage inflammatory response and metabolic dysregulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The microRNA sequencing and messenger RNA sequencing were conducted in peripheral monocytes from patients with coronary artery disease (CAD) and healthy controls. Macrophages in mouse aortas and human coronary arteries were characterized using flow cytometry and immunostaining. Atherosclerosis development was evaluated in male PCSK9 (proprotein convertase subtilisin/kexin type 9)-overexpression mice harboring myeloid cell-specific deficiency of CPE (carboxypeptidase E) or RRM2 (ribonucleotide reductase regulatory subunit M2) and challenged with a high-fat diet.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;miR487a-3p and miR6855-3p were the top microRNA candidates identified by microRNA sequencing in peripheral monocytes and validated by quantitative real-time polymerase chain reaction, with significant differences between patients with CAD and controls. Both microRNAs were lipid-inducible and secreted extracellularly. KLF5 (Krüppel-like factor 5) and IRF1 (interferon regulatory factor 1) bound to the promoter regions of miR487a-3p and miR6855-3p, respectively, to enhance their transcription. Accordingly, patients with CAD exhibited significantly elevated plasma miR487a-3p and miR6855-3p levels compared with controls, which positively correlated with blood lipid levels and Gensini score (reflecting CAD severity and prognosis). The area under the receiver operating characteristic curve (≈0.83 for each) supported their diagnostic accuracy. Of note, miR487a-3p and miR6855-3p were predominantly expressed in coronary arterial macrophages. The dramatic expansion of miR487a-3p&lt;sup&gt;+&lt;/sup&gt; and miR6855-3p&lt;sup&gt;+&lt;/sup&gt; macrophages and the elevated expression of both microRNAs in coronary arteries were positively associated with lesion area in patients with CAD. Mechanistically, transcriptomic analyses and functional assays revealed that elevated miR487a-3p or miR6855-3p promoted macrophage proinflammatory responses, lipid metabolic dysregulation, and foam cell formation. Conversely, inhibition of either microRNA alleviated ox-LDL (oxidized low-density lipoprotein)-induced macrophage inflammatory responses and lipid metabolic dysfunction. Moreover, conditioned medium from miR487a-3p- or miR6855-3p-overexpressing macrophages promoted endothelial cell apoptosis, whereas this effect was attenuated when endothelial cells were exposed to medium from ox-LDL-treated macrophages with microRNA inhibition. Furthermore, integration of downregulated genes from monocyte and macrophage messenger RNA sequencing with TargetScan-predicted targets identified CPE and RRM2 as targets of miR487a-3p and miR6855-3p, respectively. Direct binding was confirmed by dual-lucifera","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e325069"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560810","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":"Bioengineering Approaches for Nanomedicine Delivery in Therapy of Myocardial Infarction.","authors":"Jiawen Zou, Dashuai Zhu, Xiao Cheng, Ke Cheng","doi":"10.1161/ATVBAHA.126.324247","DOIUrl":"10.1161/ATVBAHA.126.324247","url":null,"abstract":"<p><p>Cardiovascular disease remains the leading cause of death globally. In particular, ischemic heart disease represents the most common condition in clinics. Adult hearts have minimal regenerative capacity. Upon myocardial infarction, the formation of activated myofibroblasts replaces the massive loss of cardiomyocytes. Nanomedicine has emerged as a promising strategy for cardiovascular disease treatment, with synthetic nanoparticles and extracellular vesicles serving as representative delivery platforms. However, directly applying these nanomedicines faces several challenges, including insufficient cardiac targeting, poor retention rate at the injured site, and potential biocompatibility concerns. To overcome these limitations, different bioengineering approaches have been adopted. In this review, we discussed the landscape of cardiovascular nanomedicine, encompassing both synthetic nanocarriers and biological carriers and targeted delivery. We further evaluated the engineering approaches to enhance carrier performance. Multiple administration routes are also compared. Collectively, these advances represent a shift toward an integrated, multifunctional delivery platform with the potential to translate cardiac nanomedicine from bench to bedside.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324247"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618309","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}