Vascular pharmacology最新文献

{"title":"Clinical outcomes and safety of sotatercept in pulmonary arterial hypertension: A systematic review and meta-analysis of randomized controlled trials","authors":"Mohammad Abdulelah ,&nbsp;Chidubem Ezenna ,&nbsp;Ancy Jenil-Franco ,&nbsp;Kevin T. Jamouss ,&nbsp;Mrinal Murali Krishna ,&nbsp;Meghna Joseph ,&nbsp;Kuan-Yu Chi ,&nbsp;Talal Dahhan","doi":"10.1016/j.vph.2025.107520","DOIUrl":"10.1016/j.vph.2025.107520","url":null,"abstract":"<div><h3>Introduction</h3><div>Pulmonary arterial hypertension (PAH) remains a life-threatening condition characterized by high morbidity and mortality. However, recent therapeutic advancements have offered a paradigm shift in terms of therapeutic goals.</div></div><div><h3>Methods</h3><div>We conducted a systematic review and meta-analysis of RCTs assessing clinical outcomes and safety of sotatercept when compared to placebo in PAH. Searches of Pubmed and Cochrane Central databases were performed through April 2025. The primary outcome was all-cause mortality. Secondary outcomes included improvements in 6MWD, WHO functional class, hemodynamics, NT-proBNP, and serious adverse events. Data were pooled using a random-effects model, with certainty of evidence assessed via GRADE methodology.</div></div><div><h3>Results</h3><div>Three RCTs comprising 601 patients were included. There was a non-significant trend toward reduced mortality (RR 0.49; 95 % CI 0.16 to 1.46; <em>p</em> = 0.11). Sotatercept was associated with significant improvements in 6MWD (MD 37.99 m; 95 % CI 6.47 to 69.52; <em>p</em> = 0.04) and WHO functional class (RR 2.04; 95 % CI 1.79 to 2.31; <em>p</em> = 0.002). Hemodynamic improvements included reductions in PVR (MD -237.73 dyn·s/cm⁵; 95 % CI -367.02 to −1.8.43; <em>p</em> = 0.02) and mPAP (MD -14.88 mmHg; 95 % CI -24.76 to −4.99; p = 0.02). Serious adverse events were similar (RR 0.79; 95 % CI 0.51 to 1.23; <em>p</em> = 0.15).</div></div><div><h3>Conclusion</h3><div>Sotatercept significantly improves functional and hemodynamic outcomes in PAH, with a favorable safety profile. While mortality benefits remain uncertain, these findings support its clinical utility as an emerging therapy in PAH.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"160 ","pages":"Article 107520"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium-glucose cotransporter 2 inhibition restores testicular microvascular perfusion via endothelial signaling in a large animal model of metabolic syndrome and heart failure","authors":"Jad Hamze ,&nbsp;Christopher Stone ,&nbsp;Dwight Douglas Harris ,&nbsp;Kelsey Muir ,&nbsp;Keertana Yalamanchili ,&nbsp;Nicholas C. Sellke ,&nbsp;Frank W. Sellke","doi":"10.1016/j.vph.2025.107530","DOIUrl":"10.1016/j.vph.2025.107530","url":null,"abstract":"<div><h3>Objective</h3><div>This study evaluates the effects of sodium-glucose cotransporter 2 (SGLT2) inhibition on testicular microvascular function and vascular signaling pathways in a swine model of metabolic syndrome (MetS) and ischemic cardiomyopathy (ICM).</div></div><div><h3>Methods</h3><div>Eleven male Yorkshire swine were fed a high-fat diet to induce MetS. At 11 weeks, ICM was induced by placing an ameroid constrictor around the left circumflex artery. After a two-week stabilization period, swine were randomized into a high-fat control (HFC) or canagliflozin-treated (HCAN, 300 mg/day) group for five weeks. Terminal harvests were performed to assess testicular perfusion, endothelial function markers, and pro-apoptotic signaling.</div></div><div><h3>Results</h3><div>Canagliflozin (CAN) significantly improved testicular perfusion (p = 0.0134). Molecular analysis showed a significant increase in p-AMPK/AMPK ratio (p = 0.0483), indicating enhanced metabolic and endothelial signaling, and a significant reduction in BAD/BCL2 ratio (p = 0.0095), consistent with a shift toward anti-apoptotic signaling. The p-eNOS/eNOS ratio trended upward in treated animals (p = 0.1007), suggesting potential augmentation of nitric oxide–mediated vasodilation. Total ERK expression was also increased (p = 0.0201), supporting engagement of MAPK pathways.</div></div><div><h3>Conclusion</h3><div>SGLT2 inhibition improved testicular microvascular perfusion and modulated key signaling ratios, including increased p-AMPK/AMPK and reduced BAD/BCL2, with a trend toward higher p-eNOS/eNOS. These findings demonstrate that canagliflozin promotes vascular survival pathways in peripheral tissues, underscoring its vasculoprotective potential beyond the myocardium.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"160 ","pages":"Article 107530"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual L/T calcium channel blocker exerts both antihypertensive and renoprotective effects in L-NAME-induced hypertension model","authors":"Peter Muiruri Kamau ,&nbsp;Yang Chen ,&nbsp;Xiaopei Yang ,&nbsp;Jinglin Li ,&nbsp;Rebecca Caroline Thuku ,&nbsp;Dawit Tadese ,&nbsp;Hao Zhang ,&nbsp;Haiying Wu ,&nbsp;Lei Luo ,&nbsp;Qiumin Lu","doi":"10.1016/j.vph.2025.107524","DOIUrl":"10.1016/j.vph.2025.107524","url":null,"abstract":"<div><div>Renal hypertension, a common form of secondary hypertension, results from kidney disease. It arises due to the narrowing of arteries connected to the kidneys, often caused by atherosclerosis. Over time, this condition can lead to kidney failure. Therapeutics for kidney protection are currently limited, prompting continual search for new renoprotective agents in the context of hypertension. Dual blockage of both L-type and T-type calcium channels has shown promise in the treatment of hypertension when compared to selective calcium channel blockers. Toddaculin has been proven to be a potent inhibitor of the T-type channel. Conserved amino acid sequence comparison, electrophysiological recordings, and Flex Station were used to evaluate and compare toddaculin effect on the Ca_V3.1 and Ca_V1.2 channels and their respective residues, transiently expressed in HEK293T cells. Intracellular Ca²⁺ was assessed using the molecular probe fluo-4-AM. They specifically investigated the impact of toddaculin on vascular smooth muscle cells (VSMCs). Toddaculin's myogenic effects were assessed using aortic rings isolated from rats within an organ bath system. In an in vivo context, a mouse model with L-NAME-induced hypertension was employed to investigate toddaculin's anti-hypertensive and renoprotective properties. We found that L1047A in Ca_V1.2, and L1456A in Ca_V3.1 are potential key binding sites for toddaculin, and that toddaculin inhibited Ca_V3.1 and Ca_V1.2 equally and dose-dependently. Toddaculin-induced decline of [Ca²⁺]_i cultured VSMCs under a laser scanning confocal microscopy. Aortic rings exposed to toddaculin demonstrated dose-dependent relaxation following KCl-induced contraction. Moreover, toddaculin exhibited significant blood pressure reduction and renoprotective effects against L-NAME-induced renal injury in mice. This finding provides an evident therapeutic potential of toddaculin as an antihypertensive drug candidate with a renoprotective effect.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"160 ","pages":"Article 107524"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Cis-regulatory elements for CRISPR-mediated transcriptional activation of the human MIR503HG locus","authors":"João P. Monteiro ,&nbsp;Francesca Vacante ,&nbsp;Azzurra L. De Pace ,&nbsp;Matthew Bennett ,&nbsp;Julie Rodor ,&nbsp;Dónal O'Carroll ,&nbsp;Joseph C. Wu ,&nbsp;Thomas Quertermous ,&nbsp;Andrew H. Baker","doi":"10.1016/j.vph.2025.107521","DOIUrl":"10.1016/j.vph.2025.107521","url":null,"abstract":"<div><div>Advances in genome annotation have revealed a striking increase in the number and complexity of non-coding RNA (ncRNA) genes, particularly multi-transcript loci that harbor long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) within the same genomic region. These loci can often function as coordinated regulatory units, with their transcription modulated by shared cis-acting regulatory elements (CREs). Traditional gene manipulation approaches, which typically target individual transcripts, are insufficient to capture the full regulatory and therapeutic potential of these complex loci. Here, we present “cis-ON” a single-vector lentiviral delivery system based on CRISPR activation (CRISPRa), designed to simultaneously upregulate multiple noncoding RNA transcripts by targeting a single CRE.</div><div>We focused on the evolutionarily conserved <em>MIR503HG</em> locus, which encodes seven lncRNA isoforms and hosts the <em>miR-424/503</em> cluster, both implicated in various cellular processes, including proliferation, angiogenesis, and endothelial-to-mesenchymal transition. Using integrative analysis of histone marks (H3K27Ac, H3K4Me3), DNase hypersensitivity, and CAGE-seq data, we identified the primary promoter of the <em>MIR503HG</em> locus. A dual fluorescent reporter screen selected optimal single guide RNAs (sgRNAs) for targeting this region. We then engineered cis-ON, a novel lentiviral system combining dCas9-VPR and sgRNA to enable a streamlined single-vector delivery approach. Transduction of primary human endothelial cells with this system robustly activated the entire locus including the <em>MIR503HG</em> isoforms and co-embedded miRNAs <em>miR-424</em> and <em>miR-503</em>, demonstrating coordinated transcriptional regulation. Additionally, the neighboring <em>LINC00629</em> lncRNA locus remained unaffected, highlighting regulatory specificity.</div><div>This approach demonstrates the feasibility of modulating complex ncRNA loci across a ∼ 10 kb genomic region by targeting a single CRE, bypassing limitations of transcriptspecific strategies. By enabling simultaneous upregulation of lncRNAs and miRNAs, the cis-ON platform provides a streamlined strategy for restoring regulatory networks disrupted in disease.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"160 ","pages":"Article 107521"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the role of STAT1-activated macrophages in abdominal aortic aneurysm: Insights from scRNA-seq and prognostic signature development","authors":"Yihui Chen ,&nbsp;Baoxing Wu ,&nbsp;Shichai Hong","doi":"10.1016/j.vph.2025.107528","DOIUrl":"10.1016/j.vph.2025.107528","url":null,"abstract":"<div><div>Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disorder with no effective drug treatment. Inflammation and macrophage infiltration in the abdominal aorta play a pivotal role in AAA development, progression, and rupture. However, the precise molecular mechanisms driving these processes remain unclear. To address this, we analyzed single-cell RNA sequencing datasets from three AAA mouse models and two healthy controls. Our findings revealed that AAA samples showed a marked increase in macrophage populations, with a shift toward pro-inflammatory M1 polarization compared to the predominantly M2 phenotype in controls. CellChat analysis revealed that the STAT1 pathway may mediate the enhanced intercellular communication between M1 and M2 macrophages. SCENIC analysis further identified STAT1 as a central transcriptional regulator in macrophages. We also developed a ten-gene inflammatory signature predictive of AAA prognosis, validated with external datasets, and confirmed STAT1's involvement via Western blotting and real-time PCR. These findings highlight the importance of macrophage polarization and STAT1-driven signaling in AAA pathogenesis. The identified gene signature offers potential for risk stratification and therapeutic targeting, advancing both mechanistic understanding and clinical management of AAA.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"160 ","pages":"Article 107528"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Balancing act: Drp1 inhibition and mitochondrial homeostasis in cardiovascular diseases","authors":"Nandini Dubey ,&nbsp;Ahsas Goyal ,&nbsp;Neeraj Parakh ,&nbsp;Rajiv Narang ,&nbsp;Sudhir Kumar Arava ,&nbsp;Arvind Kumar ,&nbsp;Mayank Yadav ,&nbsp;Harlokesh Narayan Yadav","doi":"10.1016/j.vph.2025.107531","DOIUrl":"10.1016/j.vph.2025.107531","url":null,"abstract":"<div><div>The heart is an organ that depends significantly on mitochondria to operate, since it requires a lot of energy, which mitochondria create, making them essential for the efficient functioning of the heart. The term “mitochondrial dynamics” refers to extremely dynamic organelles known as mitochondria that undergo cycles of fusion and fission to modify their appearance, distribution, and function. Drp1 or Dynamin-related protein 1, a primary fission protein, strictly regulates the elimination of damaged mitochondria by mitophagy. This ensures that the complex processes of organ and cellular dynamics in the heart are strictly managed. Phosphorylation, SUMOylation, palmitoylation, ubiquitination, S-nitrosylation, and O-GlcNAcylation are some of the posttranslational modifications (PTMs) of Drp1 that contribute to the regulation of mitochondrial dynamics. While abnormalities in mitochondrial dynamics are a crucial component of the pathophysiology of a number of cardiovascular diseases (CVDs), the heart requires an effective mitochondrial balance to sustain cardiomyocyte metabolism along with contractile activity. This review summarizes the current knowledge of the crucial function of Drp1 inhibitors in the pathophysiology of cardiovascular diseases, including myocardial ischemia–reperfusion, dysfunction of endothelial cells, smooth muscle remodelling, hypertrophy of the heart, high blood pressure, and myocardial infarction. We further highlighted the possible advantages of treating CVDs by specifically targeting Drp1.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"160 ","pages":"Article 107531"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of non-invasive low-risk criteria in patients with connective tissue disease-associated pulmonary arterial hypertension: A 12-months analysis from the INSPECTIO study","authors":"Livio Giuliani ,&nbsp;Michele D'Alto ,&nbsp;Emma Di Poi ,&nbsp;Lorenzo Dagna ,&nbsp;Federico Guerra ,&nbsp;Marco Corda ,&nbsp;Gian Piero Perna ,&nbsp;Andrea Doria ,&nbsp;Roberto Badagliacca ,&nbsp;Marco Vicenzi ,&nbsp;Edoardo Airò ,&nbsp;Matteo Toma ,&nbsp;Laura Scelsi ,&nbsp;Cristina Piccinino ,&nbsp;Natale Daniele Brunetti ,&nbsp;Carlo Mario Lombardi ,&nbsp;Fabiana Baldi ,&nbsp;Matteo Biancospino ,&nbsp;Alessia Uglietti ,&nbsp;Stefano De Santis","doi":"10.1016/j.vph.2025.107529","DOIUrl":"10.1016/j.vph.2025.107529","url":null,"abstract":"<div><h3>Background</h3><div>Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) is a progressive, high-risk subtype of PAH characterized by immune-mediated vascular remodeling, poor treatment response, and reduced survival. Real-world data on therapeutic response and risk evolution in this population remain limited.</div></div><div><h3>Methods</h3><div>This post hoc analysis of the multicenter, prospective INSPECTIO study evaluated the CTD-PAH subpopulation treated with macitentan and/or selexipag. The primary endpoint was the change in the number of non-invasive low-risk criteria (World Health Organization functional class I–II, 6-min walk distance &gt;440 m, BNP &lt;50 ng/L or NT-proBNP &lt;300 ng/L) from baseline to 12 months. Secondary endpoints included changes in risk stratification, 6MWD, BNP/NT-proBNP levels, echocardiographic and hemodynamic parameters, a comparison with the non-CTD PAH population of the study was also conducted.</div></div><div><h3>Results</h3><div>Among a total of 176 patients enrolled in the INSPECTIO study, 64 (36.4 %) had CTD-PAH. The CTD group, with a larger prevalence of systemic sclerosis (SSc) patients, was predominantly female (93.8 %) and older than the non-CTD group (66.4 vs. 59.6 years, <em>p</em> = 0.0005). The mean number of non-invasive low-risk criteria increased significantly from baseline to Month 12 (+0.20; <em>p</em> = 0.0389), with 10.9 % of CTD patients achieving three low-risk criteria at Month 12. Secondary endpoints (Investigator's risk assessment, 6MWD, BNP, NT-proBNP, echocardiographic and hemodynamic parameters, baseline therapeutic strategy, vital signs) remained collectively stable.</div></div><div><h3>Conclusions</h3><div>CTD-PAH patients showed improvement in non-invasive risk criteria and stabilization of functional, echocardiographic, and hemodynamic parameters under macitentan and/or selexipag therapy. Despite the observational nature and small sample size, this real-world analysis supports the use of risk-based treatment strategies and close monitoring in this patient population.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"160 ","pages":"Article 107529"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"‘Emerging cell-specific therapies in cardiovascular disease’","authors":"Amandeep Rashid Mondal ,&nbsp;Ashish Misra","doi":"10.1016/j.vph.2025.107516","DOIUrl":"10.1016/j.vph.2025.107516","url":null,"abstract":"<div><div>Atherosclerosis is a leading cause of cardiovascular morbidity and mortality worldwide, driven by complex interactions among various plaque cell types, including endothelial cells, macrophages, and smooth muscle cells. Traditional therapies targeting systemic risk factors such as cholesterol and blood pressure fail to directly address the underlying mechanisms governing plaque formation and progression. Recent advances in cell-specific therapies offer new avenues for targeting the cellular and molecular processes driving atherosclerosis. This Review explores innovative strategies including nanoparticles, viral vectors and CRISPR-Cas9 technology, which have the potential to modulate gene expression and behaviour within plaques cells to alleviate disease. By focusing on the specific roles of key cell types in atherosclerosis, these emerging therapies promise to provide more precise, effective, and personalised treatment options without inducing off-target effects. Moreover, insights gained from successful applications of these technologies in oncology are considered for potential repurposing in atherosclerosis-related disease. As these cell-specific approaches advance through preclinical and clinical development, they may significantly enhance our ability to treat atherosclerosis at its cellular roots, offering new hope for reducing the burden of cardiovascular disease.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"160 ","pages":"Article 107516"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resolvin D2 limits senescent cell accumulation in atherosclerotic plaques.","authors":"Masharh Lipscomb, Ignacia Salfate Del Rio, Maya Eid, Allison Rahtes, Grace Martino, Sudeshna Sadhu, Sayeed Khan, Katherine C MacNamara, Gabrielle Fredman","doi":"10.1016/j.vph.2025.107527","DOIUrl":"10.1016/j.vph.2025.107527","url":null,"abstract":"<p><p>Atherosclerosis is a non-resolving inflammatory disease, and mechanisms to promote inflammation resolution, reduce vascular injury and promote repair in atherosclerosis are unmet needs. Specialized pro-resolving mediators (SPMs) like Resolvins, in part, mediate inflammation resolution and limit atherosclerosis progression. Uncovering processes associated with their protective actions are of interest. Senescent cells are maladaptive in atherosclerosis, and their accumulation promotes necrotic core formation in plaques. The SPM Resolvin D2 (RvD2) reduces plaque necrosis in part through its G-protein coupled receptor (GPCR), called GPR18. Here, we show how RvD2 can limit senescent cell accumulation in vivo and in vitro. Loss of myeloid GPR18 in Ldlr^-/- mice led to increased accumulation of senescent cells, and RvD2 treatment in Ldlr^-/- mice led to decreased accumulation of senescent cells in plaques. We found that senescent macrophages are not readily efferocytozed due to elevated \"don't eat me\" signals called CD24 and CD47. Knockdown or blockade of these signals improved senescent macrophage clearance, but not as efficient as efferocytosis of apoptotic cells in vitro. RvD2 treatment to senescent macrophages in vitro increased Cleaved Caspase-3 (an apoptosis marker) but did not impact the levels of CD24 or CD47. RvD2 enhanced the clearance of senescent macrophages but knockdown or blockade of CD24 and CD47 were also required for efficient clearance. Our work provides a cellular mechanism in which RvD2 treatment may limit plaque necrosis through decreasing senescent macrophages in plaques.</p>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":" ","pages":"107527"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13036740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explosive discovery, surprising future: The extraordinary journey of nitroglycerin, nitroderivatives and nitric oxide","authors":"Maria Rosa Montinari ,&nbsp;Sergio Minelli ,&nbsp;John D. Horowitz ,&nbsp;Raffaele De Caterina","doi":"10.1016/j.vph.2025.107517","DOIUrl":"10.1016/j.vph.2025.107517","url":null,"abstract":"<div><div>For over 150 years, nitrates have been a cornerstone in the treatment of cardiovascular disease. Nitroglycerin — synthesized by Italian chemist Ascanio Sobrero in 1847 — was initially used in explosives, as the main component of dynamite, by Alfred Nobel. The Scottish physician Lauder Brunton first used amyl nitrite for angina in 1867, and in 1879 the English physician William Murrell described the benefits of nitroglycerin for angina pectoris. Organic nitrates, including nitroglycerin, act as nitric oxide donors, sharing the mechanism of NO release, which induces vasodilation. This paper reviews the fascinating history of nitroglycerin and nitroderivatives, the related discovery of nitric oxide as a cardiovascular signaling molecule, and the 1998 Nobel Prize awarded for this discovery. The paper also succinctly explores current and future roles of nitric oxide donors in cardiovascular treatment.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"160 ","pages":"Article 107517"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}