Vascular pharmacology最新文献

{"title":"Systemic OPA1 overexpression reshapes cardiovascular metabolism and cardiac physiology during high-fat diet feeding.","authors":"Lorenzo Da Dalt, Giulia Giancane, Francesca Fantini, Laura Castiglioni, Patrizia Uboldi, Silvia Pedretti, Nico Mitro, Annalisa Moregola, Ottavia Terenghi, Luigi Sironi, Andrea Baragetti, Giuseppe Danilo Norata","doi":"10.1016/j.vph.2026.107713","DOIUrl":"https://doi.org/10.1016/j.vph.2026.107713","url":null,"abstract":"<p><strong>Introduction: </strong>Optic atrophy 1 (OPA1) is a mitochondrial inner-membrane GTPase that coordinates mitochondrial fusion, cristae organization, and respiratory efficiency. Beyond mitochondrial bioenergetics, OPA1 contributes to cardiovascular homeostasis, including the maintenance of vascular cell function and phenotype. Although increasing OPA1 expression has been proposed to improve mitochondrial performance, the consequences of sustained OPA1-driven oxidative activation in the lipid-exposed cardiovascular system remain incompletely defined. Here, we investigated cardiac structure, tissue metabolism, and cardiomyocyte bioenergetics in mice with systemic OPA1 overexpression maintained on a high-fat diet (HFD).</p><p><strong>Methods: </strong>OPA1-overexpressing mice were fed high-fat diet for 20 weeks, followed by indirect calorimetry and echocardiographic analysis. Tissues were used for OMICs investigation and metabolic analysis.</p><p><strong>Results: </strong>OPA1-overexpressing mice displayed preserved global left-ventricular systolic function and ventricular volumes but presented reduced anterior and lateral wall thickness. Histological analysis further revealed a decrease in cardiomyocyte cross-sectional area accompanied by increased myocardial collagen deposition. Cardiac triglyceride content was elevated, whereas cholesterol content was unchanged. In neonatal cardiomyocytes, OPA1 overexpression resulted in increased oxygen consumption, with the strongest response observed in cells co-incubated with very-low-density lipoprotein. Under this lipid-rich condition, ATP-linked respiration, maximal respiration, and spare respiratory capacity were increased.</p><p><strong>Discussion: </strong>Collectively, these findings indicate that systemic OPA1 overexpression was associated with myocardial lipid accumulation and early fibrotic remodeling during HFD feeding, despite preserved systolic function. In vitro, OPA1 overexpression increased cardiomyocyte respiratory capacity under lipid-rich conditions. These data identify a context-dependent effect of OPA1 in which enhanced respiratory capacity may become maladaptive when lipid supply exceeds coordinated oxidative and storage capacity.</p>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":" ","pages":"107713"},"PeriodicalIF":3.7,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149239584","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":"Integrative genetic analyses for drug repurposing identify emodin as a candidate modulator of STAT3 signaling in abdominal aortic aneurysm.","authors":"Yingjie Liu, Zhijun Xu, Lin Deng, Chi Zhang, Xiao Ruan, Linlu Zhao, Ying Yang, Zanxin Wang, Haocheng Lu","doi":"10.1016/j.vph.2026.107711","DOIUrl":"10.1016/j.vph.2026.107711","url":null,"abstract":"<p><p>Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease lacking effective pharmacological therapies. To identify potential therapeutic targets and candidate compounds, we performed integrative genetic analyses for drug repurposing by combining Mendelian randomization (MR), summary-data-based Mendelian randomization (SMR), and Bayesian colocalization. This framework prioritized multiple druggable candidates, among which STAT3 emerged as a key regulatory node. Subsequent functional studies demonstrated that emodin suppressed vascular smooth muscle cell proliferation, migration, phenotypic switching, and inflammatory responses. These effects were accompanied by reduced STAT3 phosphorylation and nuclear localization. Molecular docking suggested a potential binding mode of emodin within the STAT3 SH2 domain, while cellular thermal shift assays demonstrated thermal stabilization of STAT3 by emodin in intact cells, consistent with target engagement. Notably, emodin and the selective STAT3 inhibitor STAT3-IN-13 produced comparable effects, and co-treatment did not yield additive efficacy, suggesting overlapping mechanisms. In vivo, emodin attenuated aneurysm development and reduced vascular inflammation in experimental models. Collectively, these findings identify emodin as a candidate modulator of AAA progression acting through suppression of STAT3-associated signaling pathways, and demonstrate the potential of genetic evidence-guided drug repurposing strategies in complex vascular diseases.</p>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":" ","pages":"107711"},"PeriodicalIF":3.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228906","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 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,&nbsp;Yiting Dong,&nbsp;Qihao Shi,&nbsp;Hongbing Meng,&nbsp;Jiawei Sun,&nbsp;Congmei Han,&nbsp;Chenjie Yan,&nbsp;Chendong Wu,&nbsp;Jing Wang,&nbsp;Adriana Georgescu,&nbsp;Keke Jin,&nbsp;Linbo Yuan","doi":"10.1016/j.vph.2026.107694","DOIUrl":"10.1016/j.vph.2026.107694","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"164 ","pages":"Article 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,&nbsp;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":"164 ","pages":"Article 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":"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}

{"title":"iPSC-derived cardiac models for exploring MLIP function in LMNA cardiomyopathy","authors":"V. Medeghini ,&nbsp;C. Ronchi ,&nbsp;C. Thairi ,&nbsp;C. Galli ,&nbsp;C. Pernici ,&nbsp;M. Ballerini ,&nbsp;R. Visone ,&nbsp;P. Occhetta ,&nbsp;M. Rasponi ,&nbsp;E. Di Pasquale","doi":"10.1016/j.vph.2026.107639","DOIUrl":"10.1016/j.vph.2026.107639","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"163 ","pages":"Article 107639"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148241531","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}