Vascular pharmacology最新文献

{"title":"Multi-omics and experimental validation reveal the proliferative mechanism of ACSL4 in pulmonary hypertension and identify potential FDA-approved drugs via in silico screening.","authors":"Wei Chen, Yiting Dong, Qihao Shi, Hongbing Meng, Jiawei Sun, Congmei Han, Chenjie Yan, Chendong Wu, Jing Wang, Adriana Georgescu, Keke Jin, Linbo Yuan","doi":"10.1016/j.vph.2026.107694","DOIUrl":"10.1016/j.vph.2026.107694","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension (PH) is a life-threatening blood vessel disorder marked by remodeling of the pulmonary arteries. A key feature of this process is the uncontrolled growth of pulmonary artery smooth muscle cells (PASMCs). Although changes in fatty acid metabolism are thought to drive this abnormal cell growth, the exact molecular mechanisms behind it are still not fully understood.</p><p><strong>Objective: </strong>This study aimed to identify key regulators of fatty acid metabolism in PH using multi-omics data and lab experiments, and to explore how they contribute to PASMC overgrowth, with the goal of uncovering new treatment targets.</p><p><strong>Methods: </strong>We analyzed PH-related transcriptome data (GSE113439) and protein interaction networks to pinpoint central fatty acid metabolism genes. Functional enrichment, immune cell infiltration, and single-cell RNA sequencing (GSE210248) were used to explore the role of a key gene, ACSL4. We then screened FDA-approved drugs for potential ACSL4 inhibitors using molecular docking and dynamics simulations. Finally, in a rat model of PH induced by chronic low oxygen and in primary PASMCs, we tested how blocking ACSL4 (with the inhibitor PRGL493 or siRNA) affected cell growth and the pathways involved.</p><p><strong>Results: </strong>ACSL4 stood out as a central player in fatty acid metabolism in PH. Its high expression was linked to changes in the immune environment and early disease stages. Functional analysis showed that ACSL4 and its related networks are involved in lipid metabolism, PPAR signaling, and ferroptosis. Virtual screening and molecular dynamics pointed to three FDA-approved drugs that bind tightly and steadily to ACSL4. In lab and animal studies, ACSL4 levels went up in lung tissue and PASMCs exposed to low oxygen, along with shifts in fatty acid profiles and increased PASMC growth. Blocking or silencing ACSL4 eased this overgrowth by helping restore normal VGLL4/YAP levels and reversing the suppression of the Hippo pathway.</p><p><strong>Conclusion: </strong>This study uncovers a novel mechanism by which ACSL4 fuels PASMC growth in PH through reshaping fatty acid metabolism and targeting the VGLL4/YAP signaling axis. Although the role of ACSL4 in pulmonary hypertension has been previously reported, its function via the VGLL4/YAP axis is a novel finding. These findings highlight a key pathway in PH progression and point to ACSL4 as a possible target for new treatments.</p>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"164 ","pages":"107694"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857762","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":"From the University of Pisa cardiovascular summer school to a multidimensional view of cardiovascular medicine.","authors":"Rosalinda Madonna, Raffaele De Caterina","doi":"10.1016/j.vph.2026.107689","DOIUrl":"10.1016/j.vph.2026.107689","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":" ","pages":"107689"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765317","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":"TUG-891-mediated FFAR4 activation attenuates vascular remodeling via suppression of aberrant browning and lipolysis in perivascular adipose tissue.","authors":"Ai Jiang, Tianjiao Wang, Xiaobing Xu, Zhang Chen, Yujuan Li, Jiahe Du, Yixuan Jiang, Xinzhi Li","doi":"10.1016/j.vph.2026.107695","DOIUrl":"10.1016/j.vph.2026.107695","url":null,"abstract":"<p><strong>Background: </strong>Free fatty acid receptor 4 (FFAR4) activation modulates adipogenesis, but this pathway has not been explored in the context of perivascular adipose tissue (PVAT) dysfunction and vascular remodeling.</p><p><strong>Methods: </strong>Adipose tissue-specific FFAR4 knockout (Adipo-Ffar4^-/-, Adipo-KO) mice were generated by crossing Adipoq-Cre and Ffar4^flox/flox (WT) mice. FeCl₃-induced PVAT injury model in abdominal aorta was established. TUG-891 (20 mg/kg/day, i.p.) was administered for 4 weeks. In vitro, FeCl₃-conditioned medium was prepared with mouse PVAT explants. Proliferation and migration of vascular smooth muscle cells (VSMCs) cultured with conditioned medium were assessed.</p><p><strong>Results: </strong>FFAR4 was particularly upregulated in abdominal aortic PVAT in response to high-fat diet feeding. TUG-891-mediated FFAR4 activation in PVAT alleviated abdominal aortic dysfunction and hyperplasia in WT mice. TUG-891 also prohibited aberrant lipolysis and browning, as evidenced by lower serum FFA levels and downregulated UCP1 expression, in a FFAR4-dependent manner. Expression of pro-remodeling genes (CCL2, MMP9, SPP1) in damaged PVAT was reduced by TUG-891. These protective effects were absent in Adipo-KO mice. In vitro, conditioned medium from FeCl₃-primed PVAT promoted VSMC proliferation and migration, which was attenuated by TUG-891 in the presence of FFAR4. Free fatty acids also enhanced VSMC proliferation and migration. These effects were abolished when using PVAT or cells from Adipo-KO mice.</p><p><strong>Conclusion: </strong>These results indicate that TUG-891 mitigates vascular hyperplasia and remodeling by activating FFAR4 in PVAT, reducing lipolysis and suppressing aberrant adipocyte browning. Targeting PVAT FFAR4 signaling may represent a promising therapeutic strategy for vascular diseases.</p>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":" ","pages":"107695"},"PeriodicalIF":3.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875557","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":"Aquaporin-1 facilitates the transport of hydrogen peroxide and nitric oxide during endothelium-dependent vasorelaxation.","authors":"Omar Echeverría Rodríguez, Sebastián Ramírez Rodríguez, Sara Daniela Hernández Torres, Héctor Riveros Rosas, Itzell A Gallardo Ortíz, Rafael Villalobos Molina, María Magdalena Vilchis Landeros","doi":"10.1016/j.vph.2026.107692","DOIUrl":"10.1016/j.vph.2026.107692","url":null,"abstract":"<p><p>Aquaporins (AQPs) are transmembrane proteins that primarily transport water, but certain isoforms also facilitate the diffusion of small neutral signaling molecules, such as hydrogen peroxide (H₂O₂) and nitric oxide (NO). However, whether AQPs mediate vascular H₂O₂ and NO transport remains poorly understood. We investigated whether AQPs facilitate the transport of these endothelium-derived relaxing factors using relaxation assays in isolated male Wistar rat aortas. Incubation with diphenyleneiodonium (non-specific NADPH oxidase inhibitor), VAS2870 (pan-NADPH oxidase inhibitor), diethyldithiocarbamate (superoxide dismutase inhibitor), exogenous peroxidase, AgNO₃ (non-selective AQP inhibitor), or bacopaside II (selective AQP1 inhibitor) significantly attenuated carbachol-stimulated endothelium-dependent relaxation. Vasorelaxation induced by exogenous H₂O₂ was reduced by AgNO₃ or bacopaside II; however, in endothelium-denuded rings, AgNO₃ - but not bacopaside II- attenuated this response. Furthermore, both AgNO₃ and bacopaside II decreased relaxation mediated by the intracellular NO donor sodium nitroprusside. Concomitantly, in endothelium-denuded segments, vasorelaxation induced by the extracellular NO donor spermine NONOate was diminished by AgNO₃, but was slightly increased by bacopaside II. Collectively, these findings suggest that during endothelium-dependent vasorelaxation, AQP1 facilitates endothelial H₂O₂ influx and subsequent NO efflux, rather than promoting their entry into vascular smooth muscle cells. Thus, our work uncovers a coordinated H₂O₂-NO signaling cascade that drives endothelium-dependent relaxation in the rat aorta via AQP1-mediated transport, providing novel insights into the biophysical mechanisms governing endothelial function.</p>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":" ","pages":"107692"},"PeriodicalIF":3.7,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857688","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":"Pan-peroxisome proliferator-activated receptor agonist IVA337 alleviates secondary lymphedema via inhibiting TGFβ/SMAD2/3 signaling pathway.","authors":"Jingjing Pang, Long Nguyen Hoang Do, Esteban Delgado, Jianan Zhao, Liam Flynn, Hongxia Liu, Michael Autieri, Xiaofeng Yang, Xiaolei Liu","doi":"10.1016/j.vph.2026.107693","DOIUrl":"10.1016/j.vph.2026.107693","url":null,"abstract":"<p><p>Lymphedema is a chronic disease characterized by impaired lymph drainage and accumulation of protein-rich interstitial fluid, which progresses to develop irreversible fibrosis. Despite its substantial clinical burden, effective pharmacological therapies that improve lymphatic function and prevent disease progression remain lacking. Given the prominent inflammatory and fibrotic responses associated with lymphedema, we investigated the therapeutic potential of IVA337 (lanifibranor), a pan-peroxisome proliferator-activated receptor (PPAR) agonist that activates PPARα, PPARβ/δ, and PPARγ, key regulators of lipid metabolism, inflammation, and fibrosis. Here, we evaluated the therapeutic efficacy of IVA337 during the early stage of surgery-induced secondary lymphedema in mice and investigated the underlying mechanisms. IVA337 administration alleviates lymphedema progression, improves lymphatic drainage, reduces dermal thickness, and resolves lymphatic vessel dilation. Mechanistically, IVA337 suppresses TGFβ/SMAD2/3 signaling pathway, reduces immune cells infiltration, and improves lymphatic vessels integrity. In human dermal lymphatic endothelial cell (HDLEC), IVA337 attenuates TGFβ induced SMAD2/3 phosphorylation and preserves the expression of cell junction Claudin5, reduces VE-Cadherin-stained cell-cell gaps. Collectively, our findings demonstrate that IVA337 protects against early-stage lymphedema by suppressing TGFβ/SMAD2/3 signaling and limiting inflammatory and fibrotic and lymphatic endothelial dysfunction. These findings identify pan-PPAR activation as a promising pharmacological strategy to preserve lymphatic function during the early phase of lymphedema and potentially prevent progressive tissue fibrosis.</p>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":" ","pages":"107693"},"PeriodicalIF":3.7,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857754","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":"Statin-mediated regulation of miRNA expression in circulating endothelial progenitor cells in hypertensive patients: A translational mechanism of vascular protection","authors":"M.S. Marozzi ,&nbsp;F. Corvasce ,&nbsp;G. De Martino ,&nbsp;M.A. Potenza ,&nbsp;C. Nacci ,&nbsp;A. Vacca ,&nbsp;M. Montagnani ,&nbsp;S. Cicco ,&nbsp;V. Desantis","doi":"10.1016/j.vph.2026.107628","DOIUrl":"10.1016/j.vph.2026.107628","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"163 ","pages":"Article 107628"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148241230","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":"Patient-specific iPSC models as predictors of therapeutic response in TTN-related dilated cardiomyopathy","authors":"C. Thairi ,&nbsp;P. Kunderfranco ,&nbsp;M. Paulis ,&nbsp;C. Galli ,&nbsp;G. Sinagra ,&nbsp;M. Dal Ferro ,&nbsp;E. Di Pasquale","doi":"10.1016/j.vph.2026.107649","DOIUrl":"10.1016/j.vph.2026.107649","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"163 ","pages":"Article 107649"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148241473","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":"Population of models and cross-phenotype translators approaches to stratify hypertrophic cardiomyopathy mutations","authors":"E. Ricci ,&nbsp;A. Fabbri ,&nbsp;J.M. Pioner ,&nbsp;R. Coppini ,&nbsp;C. Ferrantini ,&nbsp;C. Bartolucci ,&nbsp;S. Severi","doi":"10.1016/j.vph.2026.107641","DOIUrl":"10.1016/j.vph.2026.107641","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"163 ","pages":"Article 107641"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148241602","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":"N6-methyladenosine (m6A) post-transcriptional modification regulation of mRNA, an overlooked therapeutic opportunity to leverage mRNA processing in vascular smooth muscle cells","authors":"Dominick Openko,&nbsp;Michael V. Autieri","doi":"10.1016/j.vph.2026.107655","DOIUrl":"10.1016/j.vph.2026.107655","url":null,"abstract":"<div><div>In response to pathological stimuli, VSMCs modulate from a quiescent, contractile phenotype to a synthetic, non-contractile phenotype with increased migration, proliferation, and expression of matrix and pro-inflammatory cytokines. This response necessitates modification in expression of a plethora of mRNA transcripts, which often requires fine-tuning by post-translational changes in the stability of these mRNAs. N6-methyladenosine (m6A) modification can affect the fate of many mRNA transcripts in the cell, especially mRNA stability. Various m6A regulatory proteins, such as writers (methylases), erasers (demethylases), and readers (RNA binding proteins) are involved in various homeostatic processes in the cell, and can become dysregulated in disease states, contributing to vascular pathology. Recently, it has been shown that these m6A modulatory proteins can be targeted therapeutically with small molecule inhibitors to alter their expression and activity in the cell, opening up the possibility that targeting modifiers of the mRNA methylome can be leveraged as a therapeutic opportunity to treat vascular diseases. This review describes the mechanisms and explores roles of m6A modification in mRNA processing and how these changes in the VSMC transcriptome can contribute to pathogenesis and possibly treatment of vascular diseases.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"163 ","pages":"Article 107655"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006213","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":"Cellular consequences of non-ablative radiotherapy, a novel approach to ventricular tachycardias","authors":"C. Maniezzi ,&nbsp;S. Busti ,&nbsp;A.S. Maione ,&nbsp;E. Sommariva ,&nbsp;C. Florindi ,&nbsp;F. Misitano ,&nbsp;I. Anzaldi ,&nbsp;F.P. Cammarata ,&nbsp;G.I. Forte ,&nbsp;R. Catalano ,&nbsp;G.M. De Ferrari ,&nbsp;F. Lodola ,&nbsp;A. Zaza","doi":"10.1016/j.vph.2026.107635","DOIUrl":"10.1016/j.vph.2026.107635","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"163 ","pages":"Article 107635"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148241300","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}