Vascular pharmacology最新文献

{"title":"Decreased exercise-induced pulmonary capillary recruitment in pulmonary arterial hypertension.","authors":"David Langleben, Stylianos E Orfanos, Benjamin D Fox, Michele Giovinazzo, Magali Kaddis, John D Catravas","doi":"10.1016/j.vph.2026.107615","DOIUrl":"https://doi.org/10.1016/j.vph.2026.107615","url":null,"abstract":"<p><p>The human lung normally accommodates exercise-induced cardiac output increases mainly via recruitment of non-concomitantly perfused pulmonary capillaries. Recruitment is detectable by measuring the first-pass transpulmonary metabolism of ³H-benzoyl-Phe-Ala-Pro, providing an estimate of functional capillary surface area (FCSA). Pulmonary arterial hypertension (PAH) results from luminal narrowing of small precapillary arterioles, reducing downstream perfused FCSA. We hypothesized that exercising PAH patients would not be able to recruit FCSA normally. We studied two patients with severe PAH. Despite exercising to maximal dyspnea, neither could recruit FCSA. These limited data are the first direct measurements of FCSA in exercising PAH patients.</p>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":" ","pages":"107615"},"PeriodicalIF":3.5,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843614","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":"ASPYRE-1 study: An Italian multicenter prospective study on pulmonary hypertension modality of death and validation of REVEAL risk score","authors":"Silvia Papa ,&nbsp;Michele D'Alto ,&nbsp;Laura Scelsi ,&nbsp;Mauro Acquaro ,&nbsp;Francesca Adamo ,&nbsp;Carlo Albera ,&nbsp;Pietro Ameri ,&nbsp;Paola Argiento ,&nbsp;Roberto Badagliacca ,&nbsp;Renato Carignola ,&nbsp;Gavino Casu ,&nbsp;Marco Confalonieri ,&nbsp;Marco Corda ,&nbsp;Michele Correale ,&nbsp;Chiara Cresci ,&nbsp;Francesca D'Alessandro ,&nbsp;Carlo D'Agostino ,&nbsp;Raffaele De Caterina ,&nbsp;Lucrezia De Michele ,&nbsp;Elisabetta De Tommasi ,&nbsp;Stefano Ghio","doi":"10.1016/j.vph.2025.107561","DOIUrl":"10.1016/j.vph.2025.107561","url":null,"abstract":"<div><h3>Background</h3><div>Our understanding of pulmonary arterial hypertension (PAH) pathophysiology and treatment has significantly improved over time. Within this scenario we established the Italian Network on Pulmonary Arterial Hypertension (IPHNET), promoting a national prospective registry (ASPYRE-1) to collect data on contemporary PAH patients and to define the baseline features of Italian PAH patients.</div><div>The aim of our study is to show the clinical characteristics of the Italian PAH patients. This cohort of patients will be followed in the ongoing registry to provide important insight into risk stratification and mode of death.</div></div><div><h3>Methods</h3><div>Twenty-six PAH centers were initially involved in the registry. Data were collected on anthropometric measurements, medical history, vital signs, clinical signs of heart failure, physical examination, laboratory tests (hematology and clinical chemistry), WHO functional class evaluation, non-encouraged 6-min walk test (6MWT), echocardiographic imaging and right heart catheterization (RHC) of outpatients and inpatients with PAH (Group 1) diagnosis. All the centers shared a common database for the prospective follow-up of the patients.</div></div><div><h3>Results</h3><div>between May 2014 and January 2023, a total of 500 prevalent patients with clinical diagnosis of PAH were enrolled: idiopathic (40.6 %), heritable (4.6 %), associated with drug or toxins (0.8 %), associated with connective tissue disease (26.4 %), associated with HIV infection (4.8 %), associated with portal hypertension (3.8 %), associated with congenital heart disease (16,4 %), with features of venous/capillary involvement (1.4 %), others (1.2 %) were enrolled. According to the ERS/ESC guidelines risk assessment, 207 (41.4 %) patients were at low risk, and 286 (57.2 %) were at intermediate risk. According to the REVEAL 2.0 score, 352 (70.4 %) patients were at low risk (score &lt; 7), 93 (18.6 %) were at intermediate risk (score 7–8), and 55 (11 %) were at high risk (score &gt; 8),</div><div>Of the total patient population, 177 (35.4 %) received monotherapy, 222 (44.4 %) received double combination therapy, and 101 (20.2 %) received triple combination therapy.</div></div><div><h3>Conclusion</h3><div>Built as a collaborative registry of centers treating PAH patients in Italy, it holds significant promise for addressing several critical needs within the field, including patients' clinical trajectory and risk stratification.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107561"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145655841","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":"Benzo[a]pyrene exacerbates atherosclerosis by upregulating SPP1 to promote macrophage inflammation and lipid dysregulation: An integrated network toxicology, RNA-seq, and experimental validation study","authors":"Runwen Li ,&nbsp;Jieting Zheng ,&nbsp;Yongjiang Tang ,&nbsp;Aman Liu ,&nbsp;Jiang Liu ,&nbsp;Shanshan Cai","doi":"10.1016/j.vph.2026.107589","DOIUrl":"10.1016/j.vph.2026.107589","url":null,"abstract":"<div><div>Benzo[<em>a</em>]pyrene (BaP), a pervasive environmental pollutant, has been implicated in cardiovascular injury, yet its mechanistic contribution to atherosclerosis remains unclear. Here, we combined network toxicology, RNA-seq profiling, molecular simulations, and cellular validation to elucidate BaP-driven vascular effects. Integration of BaP-associated targets with atherosclerosis gene sets identified SPP1 as a key hub. Transcriptomic analysis of aortas from BaP-treated ApoE⁻/⁻ mice revealed differential expression enriched in inflammatory responses, cytokine signaling, xenobiotic metabolism, and lipid-handling pathways. STRING-based protein interaction networks and Reactome analysis further supported coordinated activation of innate immunity and metabolic dysfunction. Molecular docking and 100-ns MD simulations demonstrated stable, energetically favorable binding between BaP and SPP1. In THP-1 macrophages, BaP enhanced oxLDL-induced SPP1 expression, reduced cell viability, and promoted a foam-cell-like phenotype characterized by suppressed ABCA1 and increased CD36 and PLIN2. Silencing SPP1 partially rescued BaP-induced cytotoxicity and lipid dysregulation, confirming SPP1's functional involvement. Collectively, these findings indicate that BaP aggravates atherosclerosis through SPP1-mediated macrophage inflammation and impaired lipid metabolism, highlighting SPP1 as a potential mechanistic link and therapeutic target for pollution-exacerbated vascular disease.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107589"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147310866","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":"Smooth muscle cell phenotypic modulation during atherosclerosis","authors":"Louise Frausto ,&nbsp;Matthew L. Scott ,&nbsp;A. Wayne Orr ,&nbsp;Arif Yurdagul Jr","doi":"10.1016/j.vph.2025.107570","DOIUrl":"10.1016/j.vph.2025.107570","url":null,"abstract":"<div><div>Vascular smooth muscle cells (vSMCs) play a central role in atherosclerotic plaque development and stability through their remarkable phenotypic plasticity. In healthy vessels, contractile vSMCs maintain vascular tone and structural integrity. During atherogenesis, lipid accumulation, inflammatory cues, growth factors, and mechanical stress drive vSMC dedifferentiation, proliferation, and migration into the intima. This transition involves downregulation of contractile genes regulated by SRF-myocardin and induction of synthetic, proliferative, inflammatory, macrophage-like, or osteogenic phenotypes, mediated in part by KLF4, PDGF, TNFα, oxidized lipids, and TGFβ signaling. Mechanotransduction through integrins and ECM remodeling reinforces these phenotypic shifts, with pathological stretch, matrix stiffening, and provisional matrix deposition promoting plasticity via RhoA/ROCK, FAK, and YAP/TAZ pathways. Clonal expansion of select medial vSMCs further shapes plaque architecture, while non-coding RNAs fine-tune phenotypic modulation at the post-transcriptional level. Collectively, these processes contribute to fibrous cap thinning, impaired efferocytosis, necrotic core expansion, and vascular calcification – features of vulnerable plaques. Here, we review the molecular, mechanical, and post-transcriptional mechanisms driving vSMC phenotypic modulation in atherosclerosis, highlighting their contributions to plaque progression and instability, and discussing emerging areas that may inform future therapeutic strategies.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107570"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688374","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 “Hemodynamic markers: CFD-based prediction of cerebral aneurysm rupture risk” [Vascular Pharmacology 162 (2026) 107578]","authors":"Reza Bozorgpour","doi":"10.1016/j.vph.2026.107584","DOIUrl":"10.1016/j.vph.2026.107584","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107584"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133288","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":"Therapeutic perspective on cardiomyopathy and heart failure in older adults through the lens of chronic inflammation","authors":"Hongyu Qiu ,&nbsp;Inna P. Gladysheva","doi":"10.1016/j.vph.2026.107586","DOIUrl":"10.1016/j.vph.2026.107586","url":null,"abstract":"<div><div>Cardiomyopathy is a disorder of the myocardium characterized by structural and functional abnormalities that result in impaired cardiac mechanical and/or electrical function. Aging induces a natural, gradual decline in cardiac structure and function (cardiac aging) that increases susceptibility to cardiomyopathy and exacerbates pre-existing cardiomyopathy. Despite ongoing research, the complex, multifactorial nature of this process substantially increases the risk of heart failure and remains a significant clinical and scientific challenge. With rising global life expectancy, effective pharmacological strategies are urgently needed. Here, we discuss chronic inflammation as a key driver of cardiomyopathy in older adults and explore perspectives on anti-inflammatory interventions that may slow disease progression and improve outcomes for the older population.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107586"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146214417","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":"Exercise pulmonary hypertension in chronic thromboembolic pulmonary disease without resting pulmonary hypertension: A systematic review and meta-analysis","authors":"Filippo Biondi ,&nbsp;Sandra Ghelardoni ,&nbsp;Doralisa Morrone ,&nbsp;Raffaele De Caterina ,&nbsp;Rosalinda Madonna","doi":"10.1016/j.vph.2025.107580","DOIUrl":"10.1016/j.vph.2025.107580","url":null,"abstract":"<div><div>Exercise pulmonary hypertension (exPH) is currently defined as a mean pulmonary artery pressure to cardiac output slope (mPAP/CO slope) greater than 3 mmHg/L/min during the transition from rest to end-exercise, and a normal mPAP at rest. ExPH may represent an early marker of vascular dysfunction in patients with chronic thromboembolic pulmonary disease (CTEPD) without resting pulmonary hypertension (pH). This is one of the possible complications of pulmonary embolism and is characterized by a variable degree of exercise intolerance. Its natural history is largely unknown and its clinical management is constrained by the lack of validated prognostic markers.</div><div>We conducted a systematic review and meta-analysis to evaluate the prevalence of exPH and its prognostic role in CTEPD without resting PH. Secondary aims were to ascertain the prevalence of mPAP/CO and PAWP/CO slopes in CTEPD without resting pulmonary hypertension and in patients with post-capillary PH. Upon identification and screening, 12 studies satisfied the criteria for eligibility and were included in the systematic review, with a total of 373 patients. This data base consisted of studies with different designs. Quantitative data were meta-analyzed for each of the aims when provided by at least 5 studies. Approximately 50% of patients suffered from exPH, with a pooled prevalence of 0.50 as per random effect model and 0.44 as per fixed effect model with high heterogeneity. Mean mPAP/CO slope was 4.10 and 3.51 mmHg/L/min as per random effect meta-analysis or common effects model, respectively. The studies included did not provide evidence on the prognostic role in CTEPD without resting PH. Only a few data were reported on PAWP/CO slope and post capillary exPH. In conclusion, our systematic review indicates that ExPH is highly prevalent in CTEPD without resting PH, but its prognostic value is still to be defined.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107580"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030968","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 pleiotropic effects of sotatercept","authors":"Giovanna Manzi,&nbsp;Enrico Maggio,&nbsp;Tommaso Recchioni,&nbsp;Francesca Ileana Adamo,&nbsp;Annalisa Caputo,&nbsp;Alexandra Mihai,&nbsp;Silvia Papa,&nbsp;Giorgia Serino,&nbsp;Gianmarco Scoccia,&nbsp;Roberto Badagliacca,&nbsp;Carmine Dario Vizza","doi":"10.1016/j.vph.2025.107577","DOIUrl":"10.1016/j.vph.2025.107577","url":null,"abstract":"<div><div>Recent randomized clinical trials (RCTs) have demonstrated the efficacy of sotatercept in the treatment of pulmonary arterial hypertension (PAH), leading to its approval by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This novel first-in-class fusion protein acts as a ligand trap for select members of the transforming growth factor-beta (TGF-β) superfamily, thereby exerting a broad spectrum of biological effects. These include vascular remodeling (via Activin A and B inhibition), enhancement of angiogenesis (through modulation of BMP-9), stimulation of erythropoiesis (by targeting GDF-11), and, to a lesser extent, modulation of skeletal muscle homeostasis (through GDF-8/myostatin inhibition). This review focuses on the pleiotropic effects of sotatercept, with the aim of encouraging the reader to delve deeper into the drug's multifaceted mechanisms.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107577"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145811549","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 “Real-world observational study on pulmonary arterial hypertension: Italian cohort treated with macitentan and/or selexipag as a part of a combination treatment (INSPECTIO)” [Vascular Pharmacology 162 (2026) 107585]","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.2026.107588","DOIUrl":"10.1016/j.vph.2026.107588","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107588"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147310902","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":"RNA-seq and ChIP-seq reveal microplastics induce endothelial-mesenchymal transition via HK2-mediated histone lactylation in pulmonary hypertension","authors":"Chuyan Long ,&nbsp;Mouwen Lin ,&nbsp;Wenjie Wang ,&nbsp;Yang Liu ,&nbsp;Zixi Huang ,&nbsp;Zhenyan Xu","doi":"10.1016/j.vph.2025.107571","DOIUrl":"10.1016/j.vph.2025.107571","url":null,"abstract":"<div><div>Pulmonary hypertension (PH) is a life-threatening condition characterized by progressive pulmonary vascular remodeling, and endothelial-mesenchymal transition (EndMT) is recognized as a critical pathogenic process driving this remodeling. This study investigated the role of microplastics (MPs) in promoting EndMT in human pulmonary artery endothelial cells (HPAECs) and its underlying regulatory mechanism. We demonstrated that MPs were internalized by HPAECs, leading to significant downregulation of endothelial markers (CD31 and VE-cadherin) and upregulation of mesenchymal markers (α-SMA and vimentin), thereby promoting EndMT. In a rat model of PH induced by monocrotaline, intratracheal instillation of MPs further increased right ventricular and pulmonary arterial pressures, exacerbated vascular remodeling, and enhanced inflammatory infiltration. RNA-seq analysis revealed that MPs activated inflammatory pathways and enhanced glycolysis in HPAECs, with significant upregulation of glycolytic genes such as HK2. Knockdown of HK2 attenuated the cell viability and migratory ability of HPAECs and counteracted MP-induced EndMT. Additionally, MPs increased lactate production and histone lactylation, which were reversed by HK2 interference. ChIP-seq further confirmed the altered histone lactylation by MPs in HPAECs, including 603 genes with hyper-lactylation and 1292 genes with hypo-lactylation. Genes with hyper-lactylation were related to inflammation, and genes with hypo-lactylation were associated with epithelial/endothelial cell migration, angiogenesis, and vascular endothelial growth factor signaling pathway. Integrative analysis of the RNA-seq and ChIP-seq data identified four PH- and inflammation-associated differentially expressed genes exhibiting hyper-lactylation (FOXO3, RUNX1, TNFRSF11B, and SGK1). Among them, RT-PCR and ChIP-qPCR confirmed the upregulation and increased histone lactylation of TNFRSF11B and SGK1. These findings highlight the critical role of MPs in modulating metabolic and histone lactylation in PH and suggest potential therapeutic targets for mitigating PH progression.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"162 ","pages":"Article 107571"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696411","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}