Vascular pharmacology最新文献

{"title":"Transcellular permeability of arterial endothelium to plasma LDL, an underexplored target in treating atherosclerosis: Novel insights and potential treatment strategies","authors":"Israel O. Bolanle,&nbsp;Gaetan de Liedekerke Beaufort","doi":"10.1016/j.vph.2025.107549","DOIUrl":"10.1016/j.vph.2025.107549","url":null,"abstract":"<div><div>Ischaemic heart disease, of which atherosclerosis is the primary substrate, continues to be a leading cause of death globally. Atherosclerosis is characterised by the accumulation of cholesterol, mainly from circulating low-density lipoprotein (LDL), within the arterial wall. LDL influx is determined by the product of two variables: the concentration of LDL in plasma and the permeability of the endothelium to LDL. Lowering the former is the primary therapeutic strategy employed today. Meanwhile, lowering permeability ought to be equally beneficial, and its effect on influx would likely be multiplicative with lipid lowering, but it is currently underexplored as a target in treating atherosclerosis. Advances in electron microscopy have helped improve our understanding of the three primary routes through which LDL permeates the endothelium: transcellular (via passive and active, receptor-mediated transport that involves the movement of LDL as cargo inside caveolae), paracellular (via interendothelial/paracellular junctions), and through cells undergoing mitosis and apoptosis (leaky junctions). We have therefore highlighted in this review, based on recent advances in experimental and translational investigations viable pharmacological agents that modulate transendothelial permeability to LDL as potential treatment options for atherosclerosis.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"161 ","pages":"Article 107549"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226913","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":"Apelin in glioblastoma: A dual target for tumor and vascular intervention","authors":"Gabriela E. Wachholz ,&nbsp;Karlijn van Loon ,&nbsp;Arjan W. Griffioen","doi":"10.1016/j.vph.2025.107548","DOIUrl":"10.1016/j.vph.2025.107548","url":null,"abstract":"<div><div>Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor in adults, marked by rapid progression, profound intratumoral heterogeneity and poor prognosis despite multimodal therapy. Current standard-of-care treatments, including maximal surgical resection followed by radiotherapy and temozolomide chemotherapy, offer only modest survival benefits, with most patients facing inevitable recurrence. A defining feature of GBM is its pronounced vascular proliferation, which supports tumor progression. This has spurred interest in targeting angiogenesis as a potential treatment approach. Apelin, a peptide involved in the regulation of angiogenesis and endothelial cell proliferation, has emerged as a key player in GBM pathogenesis. The Apelin/APJ signaling pathway is implicated in promoting tumor vascularization, invasiveness, and resistance to therapy, making it a promising therapeutic target. This review explores the role of Apelin/APJ pathway in GBM progression, focusing on its contribution to angiogenesis, as well as tumor growth and invasiveness. By integrating current findings, we aim to establish the rationale for targeting Apelin signaling as a novel therapeutic strategy in GBM, with the ultimate goal of overcoming treatment resistance and improving patient outcomes.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"161 ","pages":"Article 107548"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213858","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":"Comment on “Vascular diameter determines sensitivity to soluble guanylate cyclase activation in human mesenteric and renal arteries” [Lubomirov et al., Vascular pharmacology 160 (2025) 107515]","authors":"M.S. Josef","doi":"10.1016/j.vph.2025.107556","DOIUrl":"10.1016/j.vph.2025.107556","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"161 ","pages":"Article 107556"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525795","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":"Mesenchymal progenitor cells in perivascular niches: forerunners of mesenchymal stem cells and players in tissue scarring and regeneration","authors":"Neelima Thottapillil ,&nbsp;Mirko Corselli ,&nbsp;Ian Murray ,&nbsp;Reef Hardy ,&nbsp;Mario Gomez-Salazar ,&nbsp;Joan Casamitjana ,&nbsp;Isaac Shaw ,&nbsp;Ziyi Wang ,&nbsp;Bianca Vezzani ,&nbsp;Lijun Ding ,&nbsp;Alexander Deneka ,&nbsp;Yuyuan Guo ,&nbsp;Stefania Giacovazzi ,&nbsp;Mihaela Crisan ,&nbsp;Aaron James ,&nbsp;Bruno Péault","doi":"10.1016/j.vph.2025.107533","DOIUrl":"10.1016/j.vph.2025.107533","url":null,"abstract":"<div><div>The walls of all embryonic, foetal, and adult blood vessels contain mesodermal progenitors, distributed as pericytes in capillaries and micro vessels, and fibroblastic cells in the <em>tunica adventitia</em> of larger veins and arteries. Following dissociation, selection by flow cytometry, and culture, those perivascular cells turn into <em>bona fide</em> mesenchymal stem cells of which they possess all attributes. <em>In vivo</em>, the adventitial cellular niche supports several spatially-organized subsets of mesodermal progenitors biased toward either osteo-, adipo-, or fibrogenesis, and dominated by more primitive, multi-lineage stem-like cells. Experiments in reporter mice have shown that perivascular progenitor cells play roles in tissue scarring, turnover, and regeneration, but also in pathologic fibrosis and vascular remodelling. This review briefly summarizes the phenotypes, anatomical distribution, and developmental capacities of perivascular mesenchymal progenitor cells, underlining the potential interest thereof for cell therapies, tissue engineering, and disease prediction.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"161 ","pages":"Article 107533"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008438","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":"Growth differentiation factor 15 protects against diabetic endothelial dysfunction by AMP-activated protein kinase mediation","authors":"Wen Zhao ,&nbsp;Yang Liu ,&nbsp;Zhengshuo Cui ,&nbsp;Xinxin Li,&nbsp;Han Guo,&nbsp;Xueying Chen,&nbsp;Huina Zhang","doi":"10.1016/j.vph.2025.107554","DOIUrl":"10.1016/j.vph.2025.107554","url":null,"abstract":"<div><h3>Aims</h3><div>Endothelial dysfunction is a hallmark of diabetes-associated cardiovascular complications, yet its molecular mechanisms remain incompletely elucidated. Growth differentiation factor 15 (GDF15) has emerged as an important modulator in metabolic and cardiovascular diseases; however, its role in diabetic endothelial dysfunction is poorly understood. This study aims to investigate the therapeutic potential of GDF15 in diabetic endothelial dysfunction and to elucidate the underlying mechanisms.</div></div><div><h3>Methods</h3><div><em>db/db</em> mouse aortas or high glucose/high lipid (HG/HL)-treated C57BL/6 mouse aortas were exposed to GDF15 for acute or prolonged durations. Endothelium-dependent relaxation (EDR) was evaluated using wire myography. Meanwhile, western blotting was performed to assess protein levels of nuclear factor erythroid 2-related factor 2 (NRF2), NADPH oxidase 2 (NOX2), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), total AMP-activated protein kinase (AMPK), and phosphorylated AMPK in endothelial cells treated with GDF15 in the presence or absence of HG/HL. Reactive oxygen species (ROS) production in <em>en face</em> endothelial cells of mouse aortas was measured via confocal microscopy.</div></div><div><h3>Results</h3><div>Exogenous GDF15 acute or prolonged administration markedly ameliorated HG/HL- and diabetes-induced endothelial dysfunction and excess reactive oxygen species (ROS) generation. Meanwhile, GDF15 counteracted HG/HL-induced changes in NOX2, NRF2, ACE, and ACE2 protein expression in endothelial cells. These beneficial effects of GDF15 were mechanistically linked to AMPK upregulation, as evidenced by elevated AMPK levels in GDF15-treated endothelial cells, and the suppression of GDF15's vasoprotective effects by the AMPK inhibitor Compound C.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that GDF15 ameliorates diabetic endothelial dysfunction and oxidative stress by AMPK-dependent pathways in endothelial cells. These results highlight GDF15 as a promising therapeutic target for mitigating oxidative stress and preserving diabetic endothelial dysfunction.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"161 ","pages":"Article 107554"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356176","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":"Efficacy and safety of lorundrostat in patients with uncontrolled or resistant hypertension: A systematic review and meta-analysis with trial sequential analysis","authors":"Laila Shalabi ,&nbsp;Abdelrahman M. Tawfik ,&nbsp;Bashar M. Al Zoubi ,&nbsp;Ahmad Al Othman ,&nbsp;Sofian Zreigh ,&nbsp;Mohamed Abuelazm","doi":"10.1016/j.vph.2025.107550","DOIUrl":"10.1016/j.vph.2025.107550","url":null,"abstract":"<div><h3>Background</h3><div>Uncontrolled hypertension (HTN) remains a challenge despite multiple anti-hypertensive medications. This study systematically evaluates the efficacy and safety of Lorundrostat, a novel aldosterone synthase inhibitor, in patients with uncontrolled hypertension.</div></div><div><h3>Methods</h3><div>A comprehensive search of major electronic databases was conducted until Jul 14, 2025, to identify randomized controlled trials (RCTs) comparing Lorundrostat with placebo. The primary outcomes included changes in office systolic and diastolic blood pressure (BP). A random-effects model was used to pool the data, presented as risk ratios (RR) or mean differences (MD) with 95 % confidence intervals (CIs).</div></div><div><h3>Results</h3><div>The pooled analysis of three RCTs comprising 1562 patients demonstrated that lorundrostat yielded statistically significant reductions in both office systolic BP (MD = −8.26 mmHg; 95 % CI: −10.87 to −5.64; <em>p</em> &lt; 0.0001) and diastolic BP (MD = −3.53 mmHg; 95 % CI: −5.62 to −1.43; <em>p</em> = 0.001). However, Lorundrostat was associated with increased risks of hyperkalemia (RR = 7.93; 95 % CI: 1.55 to 40.64; <em>p</em> = 0.0131), hyponatremia (RR = 1.96; 95 % CI: 1.15 to 3.35; <em>p</em> = 0.0133), hypotension (RR = 3.06; 95 % CI: 1.15 to 8.11; <em>p</em> = 0.0250), and any adverse events (RR = 1.47; 95 % CI: 1.29 to 1.67; <em>p</em> &lt; 0.0001).</div></div><div><h3>Conclusion</h3><div>Lorundrostat effectively controls blood pressure in patients with uncontrolled hypertension; however, it also increases the incidence of adverse events, and further large-scale trials are needed to confirm long-term efficacy and safety.</div><div><strong>PROSPERO ID:</strong> CRD420251107424.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"161 ","pages":"Article 107550"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259463","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":"Elastase-2 deletion prevents vascular remodeling and abdominal aortic aneurysm development in a mice model induced by angiotensin II","authors":"Fabiola Mestriner ,&nbsp;Vinicius Flora Dugaich ,&nbsp;Pedro Brüch Dantas ,&nbsp;Henrique Z. Kovacs ,&nbsp;Marcela M. Blascke de Mello ,&nbsp;Carina A. Pedersoli ,&nbsp;Rafael Menezes da Costa ,&nbsp;Maria Cecilia Jordani ,&nbsp;Leandra N.Z. Ramalho ,&nbsp;Michele M. de Castro ,&nbsp;Júlio A. Silva-Neto ,&nbsp;Rita C.A. Tostes Passaglia ,&nbsp;Mauricio Serra Ribeiro ,&nbsp;Christiane Becari","doi":"10.1016/j.vph.2025.107557","DOIUrl":"10.1016/j.vph.2025.107557","url":null,"abstract":"<div><div>Abdominal aortic aneurysm (AAA) involves the remodeling of the aortic wall extracellular matrix (ECM), compromising biomechanical support and increasing the risk of aortic dissection and rupture. Activation of the renin-angiotensin system (RAS), particularly the synthesis of angiotensin II (Ang II), plays a fundamental role in AAA initiation and progression. Elastase-2 (ELA-2), a chymotrypsin-like serine protease, contributes to tissue Ang II generation and may be a key player in AAA pathophysiology. This study investigated the effects of ELA-2 deletion in a murine model of angiotensin II-induced AAA, with particular focus on determining whether ELA-2 modulates vascular contractility and aortic relaxation in wild-type mice and whether these effects are absent in ELA-2 knockout mice. We additionally examined the cellular alterations within the aortic wall that contribute to increased reactive oxygen species generation during AAA development. Male C57BL/6 J (wild-type, WT) and ELA-2 knockout (ELA-2KO) mice, aged 10 to 15 weeks, were infused with Ang II (1500 ng/kg/min) for 28 days to induce AAA formation. Wild-type (WT) mice developed AAA, as evidenced by aortic dilation, structural remodeling, fibrosis, and inflammation. In contrast, ELA-2KO mice showed markedly reduced pathological changes following Ang II-induced AAA. Histological and biochemical analyses of the abdominal aorta revealed enhanced gelatinolytic activity, macrophage infiltration, and oxidative stress in WT mice, all of which were significantly attenuated in ELA-2KO mice. Furthermore, transcriptional profiling demonstrated that ELA-2 deletion maintained a contractile VSMC phenotype, suggesting a protective effect against maladaptive vascular remodeling. In summary, ELA-2 deficiency prevented Ang II- induced AAA formation and pathological vascular remodeling, highlighting its potential as a therapeutic target to mitigate AAA progression.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"161 ","pages":"Article 107557"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145445995","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":"The chemokine receptor CXCR4 and its ligand CXCL12 (SDF-1) localize to ependymal cilia in brain ventricles","authors":"Shahram Eisa-Beygi ,&nbsp;Kulandaisamy Arulsamy ,&nbsp;Kui Cui ,&nbsp;Hao Wu ,&nbsp;Beibei Wang ,&nbsp;Kaifu Chen ,&nbsp;Hong Chen","doi":"10.1016/j.vph.2025.107546","DOIUrl":"10.1016/j.vph.2025.107546","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"161 ","pages":"Article 107546"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041598","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":"Corrigendum to “Lack of AMP-activated protein kinase-α1 reduces nitric oxide synthesis in thoracic aorta perivascular adipose tissue” [Vascular Pharmacology 157 (2024)107437]","authors":"Abdmajid Hwej ,&nbsp;Ali Al-Ferjani ,&nbsp;Yazeed Alshuweishi ,&nbsp;Abdullah Naji ,&nbsp;Simon Kennedy ,&nbsp;Ian Salt","doi":"10.1016/j.vph.2025.107560","DOIUrl":"10.1016/j.vph.2025.107560","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"161 ","pages":"Article 107560"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530905","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":"Pulmonary veno-occlusive disease: Insights from animal models","authors":"Akiko Hata ,&nbsp;Bengisu Gur ,&nbsp;Jaspreet Kalra ,&nbsp;Amit Prabhakar","doi":"10.1016/j.vph.2025.107547","DOIUrl":"10.1016/j.vph.2025.107547","url":null,"abstract":"<div><div>Pulmonary veno-occlusive disease (PVOD) is a subtype of pulmonary hypertension (PH) with a poor prognosis. Patients with PVOD develop a gradual increase in pulmonary vascular resistance (PVR) and right heart failure. PVOD can occur sporadically (known as sporadic PVOD or sPVOD) or be inherited (known as heritable PVOD or hPVOD). The estimated incidence rate of PVOD is 0.1–0.5 cases per million, which is about ten times less frequent than that of pulmonary artery hypertension (PAH), a condition closely related to PVOD. Because many clinical features of PVOD overlap with those of PAH, PVOD patients are often misdiagnosed as PAH. There is a critical need for early and accurate diagnosis of PVOD and effective therapeutics for PVOD developed based on its underlying etiology. In this review, we highlight the similarities and distinctions between PAH and PVOD, recent advances in understanding the mechanisms of vascular remodeling in PVOD using animal models, and emerging therapeutic strategies specifically targeting PVOD informed by these insights.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"161 ","pages":"Article 107547"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056079","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}