Vascular pharmacology最新文献

{"title":"Angiogenic and anti-angiogenic factors are the shared mechanistic pathways between preeclampsia and Alzheimer's disease: Perspective and take-away","authors":"Anass M. Abbas ,&nbsp;Hayder M. Al-kuraishy ,&nbsp;Thabat Jumaah Al-Maiahy ,&nbsp;Ali I. Al-Gareeb ,&nbsp;Waheeb Alharbi ,&nbsp;Mohamed N. Fawzy ,&nbsp;Gaber El-Saber Batiha","doi":"10.1016/j.vph.2026.107583","DOIUrl":"10.1016/j.vph.2026.107583","url":null,"abstract":"<div><div>Preeclampsia (PE), a major hypertensive disorder of pregnancy, is increasingly recognized as a significant risk factor for cognitive decline and Alzheimer's disease (AD). Placental ischemia in PE leads to an anti-angiogenic state, characterized by elevated soluble FMS-like tyrosine kinase-1 (sFlt-1) and reduced placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), causing systemic endothelial dysfunction. These alterations may persist during the postpartum period, promoting cerebrovascular impairment, blood-brain barrier (BBB) disruption, and neuroinflammation. Furthermore, PE is associated with the release of AD-related proteins, including amyloid-beta (Aβ) and hyperphosphorylated tau protein. However, the potential link between AD and PE regarding the angiogenic and anti-angiogenic factors is not fully elucidated. This review aims to explore the shared pathophysiological pathways, focusing on the angiogenic and anti-angiogenic factors. The manuscript also evaluates the potential for repurposing pharmacological agents to mitigate the long-term risk of AD in women with a history of PE.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107583"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114391","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":"Real-world observational study on pulmonary arterial hypertension: Italian cohort treated with macitentan and/or selexipag as a part of a combination treatment (INSPECTIO)","authors":"Michele D'Alto ,&nbsp;Laura Scelsi ,&nbsp;Livio Giuliani ,&nbsp;Gian Piero Perna ,&nbsp;Fabiana Baldi ,&nbsp;Federico Guerra ,&nbsp;Emma Di Poi ,&nbsp;Marco Vicenzi ,&nbsp;Roberto Badagliacca ,&nbsp;Marco Corda ,&nbsp;Edoardo Airò ,&nbsp;Paolo Ferrero ,&nbsp;Pietro Ameri ,&nbsp;Francesca Bux ,&nbsp;Piergiuseppe Agostoni ,&nbsp;Carlo D'Agostino ,&nbsp;Gavino Casu ,&nbsp;Matteo Biancospino ,&nbsp;Alessia Uglietti ,&nbsp;Stefano De Santis","doi":"10.1016/j.vph.2026.107585","DOIUrl":"10.1016/j.vph.2026.107585","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary arterial hypertension (PAH) is a progressive disease associated with significant morbidity and mortality. Combination therapy targeting multiple pathways has been shown to improve clinical outcomes.</div></div><div><h3>Methods</h3><div>The INSPECTIO study was a prospective, multicenter, observational study conducted across 29 Italian centers specializing in PAH management. The study sought to explore the impact of combination therapy on disease progression and quality of life, by assessing non-invasive risk parameters, echocardiographic and hemodynamic conditions, and patient-reported outcomes (PROs). Patients with PAH at low or intermediate mortality risk, treated with macitentan and/or selexipag (as monotherapy or in combination), were enrolled. Data on non-invasive low-risk criteria (WHO Functional Class, 6-min walk distance [6MWD], and NT-proBNP), REVEAL risk scores, echocardiographic and hemodynamic parameters, and patient-reported outcomes (emPHasis-10) were collected at baseline and 12 months. A Narrative Medicine analysis complemented quantitative findings by exploring patients' experiences.</div></div><div><h3>Results</h3><div>Among 176 patients with follow-up data, the number of non-invasive low-risk criteria increased by an average of 0.15 at 12 months (<em>p</em> = 0.0167). REVEAL 2.0 and REVEAL Lite 2 scores showed significant reductions (mean changes: −1.0, <em>p</em> = 0.0142; −0.8, <em>p</em> = 0.0111, respectively). Modest changes were observed in echocardiographic and hemodynamic parameters. Narrative analysis highlighted strengthened patient-provider relationships and improved coping strategies. Safety outcomes aligned with known profiles.</div></div><div><h3>Conclusions</h3><div>The INSPECTIO study supports the effectiveness of guideline-directed therapy and regular risk assessment to optimize treatment strategies in PAH. The increase in non-invasive low-risk criteria suggests a stabilization of disease over 12 months.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107585"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120326","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":"Ion channels of the human heart: A comprehensive four-chamber analysis","authors":"Geoffrey E. Woodard","doi":"10.1016/j.vph.2026.107582","DOIUrl":"10.1016/j.vph.2026.107582","url":null,"abstract":"<div><div>The human heart exhibits remarkable chamber-specific ion channel expression patterns that underlie the distinct electrophysiological properties of atrial versus ventricular myocardium. This comprehensive review examines the molecular architecture, biophysical properties, and functional roles of 79 ion channel subunits and related proteins across all four cardiac chambers based on quantitative transcriptomic data from non-diseased donor hearts. Understanding chamber-specific expression profiles is essential for comprehending cardiac electrophysiology, arrhythmia mechanisms, and the development of chamber-selective therapeutic strategies.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107582"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120270","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":"Hemodynamic markers: CFD-based prediction of cerebral aneurysm rupture risk","authors":"Reza Bozorgpour","doi":"10.1016/j.vph.2025.107578","DOIUrl":"10.1016/j.vph.2025.107578","url":null,"abstract":"<div><div>Predicting which intracranial aneurysms will progress to rupture remains a major unmet need in neurosurgical practice. Conventional imaging provides limited insight into the hemodynamic forces acting on the aneurysm wall, yet these forces play a central role in its long-term stability. To address this limitation, we developed a patient-specific computational pipeline capable of converting routine MRA data into detailed maps of aneurysmal blood-flow dynamics. The tool reconstructs vascular geometry directly from imaging and quantifies hemodynamic biomarkers associated with rupture risk, enabling clinicians to access physiologically meaningful information that is not visible on structural imaging alone.</div><div>Using this framework, we analyzed six aneurysm cases with known longitudinal outcomes to determine whether baseline flow conditions differed between lesions that later ruptured and those that remained stable. High-resolution CFD simulations were used to compute wall shear stress (WSS), time-averaged WSS (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and endothelial cell activation potential (ECAP). Distinct hemodynamic patterns emerged: aneurysms that remained stable showed higher WSS/TAWSS and lower OSI/RRT, whereas aneurysms that ultimately ruptured exhibited low shear environments, stronger oscillatory flow, and greater endothelial activation. Regions with elevated OSI and RRT frequently coincide with vortex cores, suggesting localized flow disturbances that may serve as early indicators of wall vulnerability.</div><div>These results demonstrate that clinically acquired MRA, when paired with a dedicated computational tool, can reveal baseline hemodynamic signatures predictive of future aneurysm behavior. This approach offers a noninvasive, imaging-driven method to support clinical decision-making, refine surveillance strategies, and improve individualized management of patients with intracranial aneurysms.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107578"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840600","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":"Tirzepatide mitigates thoracic aortic aneurysm and dissection by alleviating the loss of the contractile phenotype in vascular smooth muscle cells and reducing vascular inflammation","authors":"Liao Tan ,&nbsp;Jie Liu ,&nbsp;Ruizheng Shi ,&nbsp;Yubo Liu","doi":"10.1016/j.vph.2026.107581","DOIUrl":"10.1016/j.vph.2026.107581","url":null,"abstract":"<div><h3>Background</h3><div>Thoracic aortic aneurysm and dissection (TAAD) is a kind of life-threatening cardiovascular condition with a poor prognosis, currently lacking effective drug therapies that can halt the progression of TAAD. Tirzepatide, a dual GIP and GLP-1 receptor agonist used for type 2 diabetes and weight management, has shown cardioprotective potential, yet its effect on TAAD remains unknown.</div></div><div><h3>Methods</h3><div>A TAAD model in mice was developed by providing 0.5% β-aminopropionitrile (BAPN) for 28 days.Mice were categorized into control, tirzepatide-only, BAPN, and BAPN combined with tirzepatide.Tirzepatide (10 nmol/kg) was administered daily via intraperitoneal injection. Aortic morphology, incidence of TAAD, medial degeneration, inflammation, elastin integrity, and proteoglycan deposition were assessed by gross examination and histological analyses. Inflammatory cells infiltration and signaling pathways were evaluated by immunostaining and western blotting. In parallel, platelet-derived growth factor-BB (PDGF-BB) stimulated human aortic smooth muscle cells (HASMCs) were used as an in vitro model to examine the direct effects of TZP on VSMC phenotypic modulation.</div></div><div><h3>Results</h3><div>Treatment with tirzepatide led to a significant reduction in both the formation of TAAD (from 88.9% to 50.0%) and related deaths (from 83.3% to 38.9%). It also effectively suppressed the pathological expansion of the aortic diameter in the ascending, arch, and descending regions. Histological analysis revealed improved elastic fiber integrity and reduced degradation. Tirzepatide prevented VSMC phenotypic switching, reduced inflammatory cells infiltration, and lowered IL-1β, IL-6, and MCP-1 levels. It also downregulated NLRP3 and caspase-1 expression. In vitro, TZP directly reversed PDGF-BB-induced downregulation of VSMC contractile markers (MYH11, SMA, SM22, and CNN1) and mitigated cytoskeletal and morphological changes associated with phenotypic switching.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that tirzepatide curbs the development of TAAD in mice. The underlying mechanism likely involves the suppression of the NLRP3 inflammasome priming, a consequent reduction in vascular inflammation, and the preservation of the contractile state of VSMC. These findings highlight its potential as a novel therapeutic strategy for TAAD.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107581"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086859","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":"Nebivolol in the therapeutic landscape of heart failure: Mechanisms and clinical outcomes","authors":"Edoardo Roberto Ginghina ,&nbsp;Giuseppe Biondi-Zoccai ,&nbsp;Andrea Vitali ,&nbsp;Lucia Fatima Di Napoli ,&nbsp;Giacomo Frati","doi":"10.1016/j.vph.2025.107562","DOIUrl":"10.1016/j.vph.2025.107562","url":null,"abstract":"<div><div>Heart failure (HF) remains a major global health challenge, marked by clinical heterogeneity and high morbidity, especially among elderly and comorbid patients. While β-blockers are central to HF management, conventional agents often present tolerability limitations, particularly in populations with preserved ejection fraction (HFpEF) or impaired vascular function. Nebivolol, a third-generation β-blocker characterized by high β₁-selectivity and nitric oxide-mediated vasodilation, offers a differentiated therapeutic profile with potential advantages in these subgroups.</div><div>This review synthesizes current evidence on nebivolol's pharmacologic mechanisms, including its dual action on adrenergic and endothelial pathways, as well as its antioxidant and anti-inflammatory effects. Preclinical studies and translational biomarkers support their vascular and myocardial protective actions, while the SENIORS trial provides pivotal clinical evidence demonstrating efficacy across ejection fraction spectrums in elderly HF patients. Comparative data further reinforces its tolerability and favorable metabolic impact relative to traditional β-blockers.</div><div>Nebivolol's role is also explored in guideline contexts and its potential utility in special populations such as those with renal impairment, diabetes, or cancer therapy–related cardiac dysfunction. Looking ahead, advances in pharmacogenomics, digital phenotyping, and adaptive trial designs may help personalize nebivolol therapy. This review underscores nebivolol's emerging position in the evolving landscape of HF treatment.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107562"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665316","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":"Colchicine inhibits macrophage motility and matrix degradation through microtubule disruption","authors":"Mansi Vansjariya ,&nbsp;Aaron L. Magno ,&nbsp;Fiona J. Pixley ,&nbsp;Carl J. Schultz ,&nbsp;Julie M. Proudfoot","doi":"10.1016/j.vph.2026.107587","DOIUrl":"10.1016/j.vph.2026.107587","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerosis is a chronic inflammatory process wherein macrophages play a central role in the evolution of arterial wall plaques in extracellular matrix.</div><div>Colchicine, a drug used most commonly to treat gout, reduces immune cell motility and recruitment to inflamed joints by targeting microtubules. Colchicine also reduces cardiovascular events in patients with recent acute or chronic coronary disease, but the mechanisms are incompletely understood.</div></div><div><h3>Aims</h3><div>To characterise the effect of low-dose colchicine on human and mouse macrophages, focusing on the microtubule cytoskeleton and macrophage function.</div></div><div><h3>Methods</h3><div>Human monocytes were isolated from buffy coats and differentiated into macrophages (huMDM) in culture medium. Mouse bone marrow-derived macrophages (msBMM) were extracted from C57BL/6 mice and grown in culture medium to produce mature adherent macrophages.</div></div><div><h3>Results</h3><div>HuMDM treated with 10 nM colchicine showed marked morphological and functional changes associated with disruption of the microtubule cytoskeleton. Colchicine reduced the footprint area of huMDM by almost 50% and matrix degradation by 20%. In contrast, colchicine minimally affected the morphology of msBMM. However, it reduced the density of the microtubule cytoskeleton at the leading edge of msBMM with detectable disruption of microtubules, resulting in a significant decrease in motility.</div></div><div><h3>Conclusions</h3><div>While msBMM appeared less susceptible to low-dose colchicine than huMDM, there was a measurable effect on their microtubules that resulted in reduced motility. Inhibition of huMDM matrix degradative capacity may contribute to colchicine's effect in reducing cardiovascular events.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107587"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146221347","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":"Amylin receptors as therapeutic targets in obesity: Emerging peptide-based strategies","authors":"Mokhtar Rejili ,&nbsp;Md Sadique Hussain ,&nbsp;Yumna Khan ,&nbsp;Faouzi Haouala ,&nbsp;Subbulakshmi Ganesan ,&nbsp;Samir Sahoo ,&nbsp;Amrita Pal ,&nbsp;Vimal Arora","doi":"10.1016/j.vph.2025.107563","DOIUrl":"10.1016/j.vph.2025.107563","url":null,"abstract":"<div><div>Obesity is a chronic, relapsing metabolic disorder driven by complex genetic and environmental factors, leading to an imbalance in energy regulation. Despite the presence of GLP-1 receptor agonists with induced mild weight loss, there are significant unmet clinical needs with poor efficacy and tolerability problems. Amylin, a neuroendocrine hormone co-released with insulin, controls hunger, gastric motility, glucagon secretion, and energy metabolism via divergent amylin receptor (AMYR) subtypes (1–3), namely the calcitonin receptor (CTR) and the receptor activity-modifying proteins (RAMPs). Novel insight into the molecular make-up of AMYRs and central signaling reinforces its key function in modulating homeostatic and hedonic feeding mechanisms. The article is a review of the emerging preclinical and clinical data regarding the application of peptide-based amylin receptor agonists (AMYRAs), including pramlintide and cagrilintide, KBP-series DACRAs, and investigational drugs, including ZP8396 and amycretin. The agents show enhanced pharmacokinetics, synergy with GLP-1 receptor agonist, and favorable impact on weight regulation and metabolic plasticity. Genetic CALCR and RAMP mutations, new delivery approaches, and dual therapy by digital health technologies and bariatric surgery are also discussed in this review. Of particular interest, amylin-derived medications can have advantages over weight loss but definite disease-modifying action remains to be determined. Taken together, AMYRAs represent a potential category of therapeutics with promising disease-modifying effects that goes beyond weight loss, providing fresh perspectives for precision obesity management by 2030.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107563"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679105","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":"Endothelial-to-mesenchymal transition primes vascular endothelial cells toward an osteochondrogenic fate","authors":"Franceska Kishta ,&nbsp;Ignacio Fernando Hall ,&nbsp;Guanliang Li ,&nbsp;Tanushree Tripathi ,&nbsp;Matthieu Vermeren ,&nbsp;Justyna Cholewa-Waclaw ,&nbsp;Fiona Rossi ,&nbsp;Bruno M. Péault ,&nbsp;Julie Rodor ,&nbsp;Abdelaziz Beqqali ,&nbsp;Judith C. Sluimer ,&nbsp;Mihaela Crisan ,&nbsp;Andrew H. Baker","doi":"10.1016/j.vph.2025.107579","DOIUrl":"10.1016/j.vph.2025.107579","url":null,"abstract":"<div><div>Endothelial-to-mesenchymal transition (EndMT), in which endothelial cells (ECs) lose their endothelial identity and acquire mesenchymal-like features, contributes to vascular dysfunction and remodeling in atherosclerosis. However, the fate and function of these cells remain unclear. Here, we investigated their differentiation potential and functional properties to define how EndMT contributes to vascular dysfunction.</div><div>Human umbilical vein ECs (HUVECs) were treated with transforming growth factor-β2 (TGF-β2) and interleukin-1β (IL-1β) for seven days to induce EndMT. Mesenchymal stem/stromal cell (MSC) identity was assessed by flow cytometry for canonical markers (CD44, CD73, CD105, CD90). Differentiation states were evaluated using published single-cell RNA sequencing (scRNA-seq) data of EndMT-treated HUVECs and validated under lineage-specific culture environments. <em>In vivo</em> analysis was performed using scRNA-seq data from EC lineage reporter mice in atherosclerosis models.</div><div>EndMT-treated HUVECs displayed an intermediate mesenchymal phenotype, expressing CD44, CD73 and CD105 but lacking CD90, failing to meet MSC criteria. Potency analysis showed that 77 % of EndMT-treated HUVECs remained oligopotent, while 19 % acquired osteogenic and chondrogenic potential, accompanied by activation of lineage-associated transcriptional programs (<em>RUNX2</em>, <em>BMPR1A</em>, <em>NOTCH2</em>, <em>WNT5A</em>; <em>CD151</em>, <em>ANXA6</em>, <em>DCN</em>). <em>In vivo</em>, endothelial lineage-traced cells in atherosclerotic mice formed an EndMT cluster enriched for osteogenic and chondrogenic gene programs, including ossification and cartilage development pathways.</div><div>We define a primed oligopotent state of EndMT-derived cells both <em>in vitro</em> and <em>in vivo</em>, marked by transition toward osteogenic and chondrogenic fates. These findings suggest that EndMT contributes to atherosclerosis by generating osteogenic- and chondrogenic-like cells, linking endothelial dysfunction to vascular calcification in disease.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107579"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879118","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":"Hypothalamic regulation of obesity: Revealing the therapeutic potential of a novel anti-obesity peptide","authors":"Yi Ning Choo ,&nbsp;Ram Narayanan ,&nbsp;Vetriselvan Subramaniyan","doi":"10.1016/j.vph.2025.107553","DOIUrl":"10.1016/j.vph.2025.107553","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"161 ","pages":"Article 107553"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","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}