{"title":"Pre-eclampsia with inflammatory and pro-resolving mediator fluctuations - contributions from hemolytic protozoan parasites.","authors":"Kevin Roe","doi":"10.1016/j.vph.2025.107552","DOIUrl":"https://doi.org/10.1016/j.vph.2025.107552","url":null,"abstract":"<p><p>Pre-eclampsia (PE) and eclampsia are inflammatory hypertension diseases which have caused millions of global fatalities among pregnant women, and their pathogenesis has been a centuries-long mystery. Substantial experimental evidence, including extensive cytokine signatures, symptoms, characteristics and drug interactions, suggest initiation by hemolytic protozoan parasite infections which provide heme and iron for reactivation of iron-deprived bacterial and/or viral infections. However, there are unexplained PE and eclampsia secondary characteristics: (1) Why are endothelial dysfunction and vascular inflammation ubiquitous in pregnancies complicated by PE and eclampsia? (2) Why does pregnancy termination resolve the inflammation of pregnancies complicated by PE and eclampsia? (3) Why do omega-3 polyunsaturated fatty acids, including DHA and EFA and their derived resolvins, have decreased blood levels, whereas omega-6 polyunsaturated fatty acids have elevated levels? (4) Why is low-dose aspirin therapy frequently effective in preventing PE and eclampsia? There are now plausible explanations for these secondary characteristics. These explanations also support the hypothesis that PE and eclampsia are diseases induced by bacterial or viral infections concurrent with a hemolytic protozoan parasite infection, with reactivated infections inducing chronic inflammation. This also causes abnormal fluctuations in special pro-resolving mediators, including lipoxins, resolvins, protectins and maresins, which would normally participate in resolving acute inflammations.</p>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":" ","pages":"107552"},"PeriodicalIF":3.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309384","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}
Yi Ning Choo, Ram Narayanan, Vetriselvan Subramaniyan
{"title":"Hypothalamic regulation of obesity: Revealing the therapeutic potential of a novel anti-obesity peptide.","authors":"Yi Ning Choo, Ram Narayanan, Vetriselvan Subramaniyan","doi":"10.1016/j.vph.2025.107553","DOIUrl":"10.1016/j.vph.2025.107553","url":null,"abstract":"<p><p>Obesity is a chronic, complex condition defined by excessive fat buildup due to an imbalance between caloric consumption and energy expenditure. The significant global rise in prevalence of obesity is associated with numerous comorbidities, such as cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. Conventional management approaches, including diet, exercise, pharmacotherapy, and bariatric surgery, may demonstrate restricted long-term effectiveness owing to inadequate adherence and physiological adjustments. Recent advancements in neuroscience underscore the hypothalamus as a pivotal regulator of energy balance via essential nuclei, including the arcuate nucleus (ARC), paraventricular nucleus (PVN), lateral hypothalamic area (LHA), and ventromedial nucleus (VMN). This review examines the therapeutic potential of a new anti-obesity peptide that targets hypothalamic signalling pathways. Preclinical and clinical evidence endorses the utilization of glucagon-like peptide-1 receptor (GLP-1R) agonists and novel multi-receptor drugs such as AMG 133, which integrate GLP-1R activation with glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonism. These therapies exhibit improved weight reduction and metabolic enhancement. Moreover, the integration of hypothalamic peptide therapy with lifestyle modifications or post-bariatric care provides synergistic advantages. Notwithstanding favorable results, peptide therapy encounters obstacles such as administration methods, sustained effectiveness, and expense. Overcoming these obstacles is crucial for the effective implementation of peptide-based treatments in sustained clinical obesity control.</p>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":" ","pages":"107553"},"PeriodicalIF":3.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145303630","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 endothelium at the crossroads of multi-organ pathology: Insights from organ-on-chip models.","authors":"Swachhatoa Ghosh, Praphulla C Shukla, Soumen Das","doi":"10.1016/j.vph.2025.107551","DOIUrl":"10.1016/j.vph.2025.107551","url":null,"abstract":"<p><p>Endothelial barrier function is indispensable in maintaining vascular-tissue-organ homeostasis. Altered release of vasoactive substances along with fluctuating shear stress patterns result in an impaired barrier function leading to transmigration of blood components, tumor infiltrates and pathogens. Organ-on-chip (OoC) technology leverage microfabrication techniques to develop dynamic, three-dimensional (3D) in vitro platforms that closely mimic the structural and functional characteristics of human tissues, including the vasculature. These systems offer powerful tools for modeling disease mechanisms with high physiological relevance and are increasingly utilized in drug development, diagnostics, and therapeutic screening. By integrating biomimetic vascular environments, OoC platforms allow for the investigation of how endothelial barrier disruption, inflammatory signaling, and mechanical cues contribute to pathophysiology. Importantly, since endothelial dysfunction often precedes clinical symptoms, these models offer promising avenues for early disease detection and intervention. Together, these approaches provide a roadmap for using organ-on-chip systems to dissect vascular contributions to disease and to improve predictive, human-relevant preclinical models.</p>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":" ","pages":"107551"},"PeriodicalIF":3.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276013","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}
Laila Shalabi , Abdelrahman M. Tawfik , Bashar M. Al Zoubi , Ahmad Al Othman , Sofian Zreigh , Mohamed Abuelazm
{"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 , Abdelrahman M. Tawfik , Bashar M. Al Zoubi , Ahmad Al Othman , Sofian Zreigh , 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> < 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> < 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":"2025-10-09","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":"Transcellular permeability of arterial endothelium to plasma LDL, an underexplored target in treating atherosclerosis: Novel insights and potential treatment strategies","authors":"Israel O. Bolanle, 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":"2025-10-02","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}
Gabriela E. Wachholz , Karlijn van Loon , Arjan W. Griffioen
{"title":"Apelin in glioblastoma: A dual target for tumor and vascular intervention","authors":"Gabriela E. Wachholz , Karlijn van Loon , 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":"2025-09-30","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}
Akiko Hata , Bengisu Gur , Jaspreet Kalra , Amit Prabhakar
{"title":"Pulmonary veno-occlusive disease: Insights from animal models","authors":"Akiko Hata , Bengisu Gur , Jaspreet Kalra , 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":"2025-09-10","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}
Neelima Thottapillil , Mirko Corselli , Ian Murray , Reef Hardy , Mario Gomez-Salazar , Joan Casamitjana , Isaac Shaw , Ziyi Wang , Bianca Vezzani , Lijun Ding , Alexander Deneka , Yuyuan Guo , Stefania Giacovazzi , Mihaela Crisan , Aaron James , Bruno Péault
{"title":"Mesenchymal progenitor cells in perivascular niches: forerunners of mesenchymal stem cells and players in tissue scarring and regeneration","authors":"Neelima Thottapillil , Mirko Corselli , Ian Murray , Reef Hardy , Mario Gomez-Salazar , Joan Casamitjana , Isaac Shaw , Ziyi Wang , Bianca Vezzani , Lijun Ding , Alexander Deneka , Yuyuan Guo , Stefania Giacovazzi , Mihaela Crisan , Aaron James , 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":"2025-09-04","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":"Multi-omics identification of quantitative trait loci associated with vascular pathogenesis and diagnostic potential in chronic venous disease","authors":"Cheng-Hsun Chuang , Hsiao-Hsuan Huang , Yi-Syuan Wu , Nien-Che Ho , Chi-Ting Huang , Yi-Chen Huang , Hsien-Da Huang , Shun-Long Weng , Meng-Lin Lee , Kuang-Wen Liao","doi":"10.1016/j.vph.2025.107532","DOIUrl":"10.1016/j.vph.2025.107532","url":null,"abstract":"<div><div>Chronic venous disease (CVD) is a prevalent vascular disorder with a poorly characterized genetic basis. In this study, we employed an integrative omics strategy combining genome-wide association studies (GWAS), expression quantitative trait loci (eQTL) mapping, endothelial cell functional assays, and transcriptomic correlation analysis to elucidate the molecular architecture of CVD. A GWAS conducted in a Taiwanese population identified two CVD-associated single nucleotide polymorphisms: VSTM2L rs1998049 and DPYSL2 rs1442887. Through eQTL analysis and endothelial functional assays, four QTLs (<em>VSTM2L</em>, <em>RPRD1B</em>, <em>SAMHD1</em>, and <em>PNMA2</em>) were found to significantly affect VEGF consumption, vWF expression, and endothelial tube formation. Co-expression and correlation analyses further linked these QTLs to key vascular effector genes, including <em>VEGF</em>, <em>vWF</em>, <em>MMP9</em>, and <em>CCM2</em>. A logistic regression model based on QTL expression profiles demonstrated high diagnostic performance (area under the curve, AUC = 0.898), highlighting their translational potential. These findings offer novel insights into the functional genomics of CVD, particularly in relation to vascular remodeling, endothelial dysfunction, and inflammation. They also demonstrate the utility of multi-omics integration for biomarker discovery in complex vascular disorders.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"160 ","pages":"Article 107532"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925368","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}