Vascular pharmacology最新文献

{"title":"Sodium nitroprusside infusion in patients with advanced heart failure","authors":"Stefano Ghio ,&nbsp;Egidio Traversi ,&nbsp;Roberto Maestri ,&nbsp;Rita Camporotondo ,&nbsp;Angelo Caporotondi ,&nbsp;Alessandra Caprino ,&nbsp;Alessandro Fasolino ,&nbsp;Giampaolo Guazzotti ,&nbsp;Laura Scelsi ,&nbsp;Annalisa Turco ,&nbsp;Maria Teresa La Rovere","doi":"10.1016/j.vph.2024.107395","DOIUrl":"10.1016/j.vph.2024.107395","url":null,"abstract":"<div><h3>Aims</h3><p>Advanced heart failure (AdvHF) poses significant treatment challenges, particularly when mechanical circulatory support or transplant options are unavailable, highlighting a gap in evidence-based medical management. The aim of this study was to evaluate the safety and effectiveness of sodium nitroprusside infusion (SNP) for enhancing systemic and renal perfusion in patients with AdvHF, with or without concomitant inotropic support.</p></div><div><h3>Methods and results</h3><p>We retrospectively analyzed the medical records of 406 patients with AdvHF admitted between October 2014 and September 2018 who received nocturnal SNP infusions for at least one week. In 55 patients with symptomatic hypotension or signs of peripheral hypoperfusion (differential systemic BP &lt; 15 mmHg), continuous dobutamine infusion was added. In a subset of 155 patients who required multiple hospitalizations (median 3), data from the last hospitalization were used. No symptomatic hypotension leading to discontinuation of SNP (mean dose: 0.5 ± 0.1 μg/kg/min) was reported. Patients showed a significant increase in differential systemic blood pressure after infusion (29.2 ± 8.1 to 36.8 ± 11.6 mmHg, <em>p</em> &lt; 0.001) independent of dobutamine use.</p><p>Administration of SNP and dobutamine resulted in greater weight loss compared to SNP alone (−5.33 ± 7.02 vs −3.32 ± 4.0 kg, <em>p</em> &lt; 0.003), but it was also associated with a significant increase in creatinine levels compared to SNP alone (+0.24 ± 0.87 vs +0.02 ± 0.43, <em>p</em> = 0.005).</p></div><div><h3>Conclusions</h3><p>The results show that SNP is a safe therapeutic choice in AdvHF patients with or without concomitant inotropic support and highlight the potential efficacy of nitroprusside in improving systemic and renal perfusion in these advanced patients.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"156 ","pages":"Article 107395"},"PeriodicalIF":3.5,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535510","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":"Zinc alpha 2-glycoprotein associates with features of plaque stability in patients with carotid atherosclerosis","authors":"Amedeo Tirandi ,&nbsp;Federico Carbone ,&nbsp;Aldo Bonaventura ,&nbsp;Maria Bertolotto ,&nbsp;Silvia Minetti ,&nbsp;Simon Kraler ,&nbsp;Giovanni G. Camici ,&nbsp;Fabrizio Montecucco ,&nbsp;Luca Liberale","doi":"10.1016/j.vph.2024.107398","DOIUrl":"10.1016/j.vph.2024.107398","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"156 ","pages":"Article 107398"},"PeriodicalIF":3.5,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432910","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":"Fluorinated perhexiline derivative attenuates vascular proliferation in pulmonary arterial hypertension smooth muscle cells","authors":"Kayleigh Griffiths ,&nbsp;Roger J. Grand ,&nbsp;Ian Horan ,&nbsp;Michelangelo Certo ,&nbsp;Ross C. Keeler ,&nbsp;Claudio Mauro ,&nbsp;Chih-Chung Tseng ,&nbsp;Iain Greig ,&nbsp;Nicholas W. Morrell ,&nbsp;Matteo Zanda ,&nbsp;Michael P. Frenneaux ,&nbsp;Melanie Madhani","doi":"10.1016/j.vph.2024.107399","DOIUrl":"10.1016/j.vph.2024.107399","url":null,"abstract":"<div><p>Increased proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs) is recognised as a universal hallmark of pulmonary arterial hypertension (PAH), in part related to the association with reduced pyruvate dehydrogenase (PDH) activity, resulting in decreased oxidative phosphorylation of glucose and increased aerobic glycolysis (Warburg effect). Perhexiline is a well-recognised carnitine palmitoyltransferase-1 (CPT1) inhibitor used in cardiac diseases, which reciprocally increases PDH activity, but is associated with variable pharmacokinetics related to polymorphic variation of the cytochrome P450-2D6 (CYP2D6) enzyme, resulting in the risk of neuro and hepatotoxicity in ‘slow metabolisers’ unless blood levels are monitored and dose adjusted. We have previously reported that a novel perhexiline fluorinated derivative (FPER-1) has the same therapeutic profile as perhexiline but is not metabolised by CYP2D6, resulting in more predictable pharmacokinetics than the parent drug. We sought to investigate the effects of perhexiline and FPER-1 on PDH flux in PASMCs from patients with PAH. We first confirmed that PAH PASMCs exhibited increased cell proliferation, enhanced phosphorylation of AKT^Ser473, ERK 1/2^{Thr202/Tyr204} and PDH-E1α^Ser293, indicating a Warburg effect when compared to healthy PASMCs. Pre-treatment with perhexiline or FPER-1 significantly attenuated PAH PASMC proliferation in a concentration-dependent manner and suppressed the activation of the AKT^Ser473 but had no effect on the ERK pathway. Perhexiline and FPER-1 markedly activated PDH (seen as dephosphorylation of PDH-E1α^Ser293), reduced glycolysis, and upregulated mitochondrial respiration in these PAH PASMCs as detected by Seahorse analysis. However, both perhexiline and FPER-1 did not induce apoptosis as measured by caspase 3/7 activity. We show for the first time that both perhexiline and FPER-1 may represent therapeutic agents for reducing cell proliferation in human PAH PASMCs, by reversing Warburg physiology.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"156 ","pages":"Article 107399"},"PeriodicalIF":3.5,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1537189124001253/pdfft?md5=8391d72e7918e2a189c9e5ed43fb60e6&pid=1-s2.0-S1537189124001253-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ex vivo study on the human blood neutrophil circadian features and effects of alpha1-antitrypsin and lipopolysaccharide","authors":"Julia Held ,&nbsp;Kokilavani Sivaraman ,&nbsp;Sabine Wrenger ,&nbsp;Wenzhang Si ,&nbsp;Tobias Welte ,&nbsp;Stephan Immenschuh ,&nbsp;Sabina Janciauskiene","doi":"10.1016/j.vph.2024.107396","DOIUrl":"10.1016/j.vph.2024.107396","url":null,"abstract":"<div><h3>Aims</h3><p>Neutrophils perform various functions in a circadian-dependent manner; therefore, we investigated here whether the effect of alpha1-antitrypsin (AAT), used as augmentation therapy, is dependent on the neutrophil circadian clock. AAT is a vital regulator of neutrophil functions, and its qualitative and/or quantitative defects have significant implications for the development of respiratory diseases.</p></div><div><h3>Methods</h3><p>Whole blood from 12 healthy women age years, mean (SD) 29.92 (5.48) was collected twice daily, 8 h apart, and incubated for 30 min at 37 °C alone or with additions of 2 mg/ml AAT (Respreeza) and/or 5 μg/ml lipopolysaccharide (LPS) from <em>Escherichia coli</em>. Neutrophils were then isolated to examine gene expression, migration and phagocytosis.</p></div><div><h3>Results</h3><p>The expression of <em>CD14</em>, <em>CD16</em>, <em>CXCR2</em> and <em>SELL</em> (encoding CD62L) genes was significantly higher while <em>CDKN1A</em> lower in the afternoon than in the morning neutrophils from untreated blood. Neutrophils isolated in the afternoon had higher migratory and phagocytic activity. Morning neutrophils isolated from AAT-pretreated blood showed higher expression of <em>CXCR2</em> and <em>SELL</em> than those from untreated morning blood. Pretreatment of blood with AAT enhanced migratory properties of morning but not afternoon neutrophils. Of all genes analysed, only <em>CXCL8</em> expression was strongly upregulated in morning and afternoon neutrophils isolated from LPS-pretreated blood, whereas <em>CXCR2</em> expression was downregulated in afternoon neutrophils. The addition of AAT did not reverse the effects of LPS.</p></div><div><h3>Significance</h3><p>The circadian clock of myeloid cells may affect the effectiveness of various therapies, including AAT therapy used to treat patients with AAT deficiency, and needs further investigation.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"156 ","pages":"Article 107396"},"PeriodicalIF":3.5,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427711","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":"Novel NLRP3 inhibitor INF195: Low doses provide effective protection against myocardial ischemia/reperfusion injury","authors":"Simone Gastaldi ,&nbsp;Magalì Giordano ,&nbsp;Federica Blua ,&nbsp;Chiara Rubeo ,&nbsp;Valentina Boscaro ,&nbsp;Saveria Femminò ,&nbsp;Stefano Comità ,&nbsp;Eleonora Gianquinto ,&nbsp;Vanessa Landolfi ,&nbsp;Elisabetta Marini ,&nbsp;Margherita Gallicchio ,&nbsp;Francesca Spyrakis ,&nbsp;Pasquale Pagliaro ,&nbsp;Massimo Bertinaria ,&nbsp;Claudia Penna","doi":"10.1016/j.vph.2024.107397","DOIUrl":"10.1016/j.vph.2024.107397","url":null,"abstract":"<div><h3>Background</h3><p>Several factors contribute to ischemia/reperfusion injury (IRI), including activation of the NLRP3 inflammasome and its byproducts, such as interleukin-1β (IL-1β) and caspase-1. However, NLRP3 may paradoxically exhibit cardioprotective properties. This study aimed to assess the protective effects of the novel NLRP3 inhibitor, INF195, both <em>in vitro</em> and <em>ex vivo</em>.</p></div><div><h3>Methods</h3><p>To investigate the relationship between NLRP3 and myocardial IRI, we synthetized a series of novel NLRP3 inhibitors, and investigated their putative binding mode <em>via</em> docking studies. Through <em>in vitro</em> studies we identified INF195 as optimal for NLRP3 inhibition. We measured infarct-size in isolated mouse hearts subjected to 30-min global ischemia/one-hour reperfusion in the presence of three different doses of INF195 (5, 10, or 20-μM). We analyzed caspase-1 and IL-1β concentration in cardiac tissue homogenates by ELISA. Statistical significance was determined using one-way ANOVA followed by Tukey's test.</p></div><div><h3>Results and conclusion</h3><p>INF195 reduces NLRP3-induced pyroptosis in human macrophages. Heart pre-treatment with 5 and 10-μM INF195 significantly reduces both infarct size and IL-1β levels. Data suggest that intracardiac NLRP3 activation contributes to IRI and that low doses of INF195 exert cardioprotective effects by reducing infarct size. However, at 20-μM, INF195 efficacy declines, leading to a lack of cardioprotection. Research is required to determine if high doses of INF195 have off-target effects or dual roles, potentially eliminating both harmful and cardioprotective functions of NLRP3. Our findings highlight the potential of a new chemical scaffold, amenable to further optimization, to provide NLRP3 inhibition and cardioprotection in the ischemia/reperfusion setting.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"156 ","pages":"Article 107397"},"PeriodicalIF":3.5,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S153718912400123X/pdfft?md5=7b2301213b9f44bacdfc9fe1a9b13cfa&pid=1-s2.0-S153718912400123X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma proteins associate with carotid plaques and predict incident atherosclerotic cardiovascular events","authors":"Andrea Baragetti ,&nbsp;Liliana Grigore ,&nbsp;Elena Olmastroni ,&nbsp;Elisa Mattavelli ,&nbsp;Alberico Luigi Catapano","doi":"10.1016/j.vph.2024.107394","DOIUrl":"10.1016/j.vph.2024.107394","url":null,"abstract":"<div><h3>Purpose</h3><p>Performing non-invasive carotid imaging is challenging, owing inter-operator variability and organizational barriers, but plasma proteomics can offer an alternative. We sought plasma proteins that associate with the presence of carotid plaques, their number and predict the incidence of clinically overt atherosclerotic cardiovascular events (ASCVD) above currently recognized risk factors in “apparently healthy” subjects.</p></div><div><h3>Methods</h3><p>We studied the plasma levels of 368 proteins in 664 subjects from the PLIC study, who underwent an ultrasound imaging screening of the carotids to check for the presence of plaques. We clustered, by artificial intelligence (A.I.), the proteins that associate with the presence, the number of plaques and that predict incident ASCVDs over 22 years (198 events were registered).</p></div><div><h3>Findings</h3><p>299/664 subjects had at least 1 carotid plaque (1+) (77 with only one plaque, 101 with 2 plaques, 121 with ≥3 plaques (3+)). The remaining 365 subjects with no plaques acted as controls. 106 proteins were associated with 1+ plaques, but 97 proteins significantly predicted 3+ plaques only (AUC = 0.683 (0.601–0.785), <em>p</em> &lt; 0.001), when considered alone.</p><p>A.I. underscored 87 proteins that improved the performance of the classical risk factors both in detecting 3+ plaques (AUC = 0.918 (0.887–0.943) versus risk factors alone, AUC = 0.760 (0.716–0.801), <em>p</em> &lt; 0.001) and in predicting the incident ASCVD (AUC = 0.739 (0.704–0.773) vs risk factors alone AUC = 0.559 (0.521–0.598), <em>p</em> &lt; 0.001). The chemotaxis/migration of leukocytes and interleukins/cytokines signaling were biological pathways mostly represented by these proteins.</p></div><div><h3>Discussion and conclusions</h3><p>Plasma proteomics marks the number of carotid plaques and improve the prediction of incidence ASCVDs in apparently healthy subjects.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"156 ","pages":"Article 107394"},"PeriodicalIF":4.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311914","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 life cycle of a capillary: Mechanisms of angiogenesis and rarefaction in microvascular physiology and pathologies","authors":"Declan Manning,&nbsp;Ernesto J. Rivera,&nbsp;L. Fernando Santana","doi":"10.1016/j.vph.2024.107393","DOIUrl":"10.1016/j.vph.2024.107393","url":null,"abstract":"<div><p>Capillaries are the smallest blood vessels (&lt;10 μm in diameter) in the body and their walls are lined by endothelial cells. These microvessels play a crucial role in nutrient and gas exchange between blood and tissues. Capillary endothelial cells also produce vasoactive molecules and initiate the electrical signals that underlie functional hyperemia and neurovascular coupling. Accordingly, capillary function and density are critical for all cell types to match blood flow to cellular activity. This begins with the process of angiogenesis, when new capillary blood vessels emerge from pre-existing vessels, and ends with rarefaction, the loss of these microvascular structures. This review explores the mechanisms behind these processes, emphasizing their roles in various microvascular diseases and their impact on surrounding cells in health and disease. We discuss recent work on the mechanisms controlling endothelial cell proliferation, migration, and tube formation that underlie angiogenesis under physiological and pathological conditions. The mechanisms underlying functional and anatomical rarefaction and the role of pericytes in this process are also discussed. Based on this work, a model is proposed in which the balance of angiogenic and rarefaction signaling pathways in a particular tissue match microvascular density to the metabolic demands of the surrounding cells. This negative feedback loop becomes disrupted during microvascular rarefaction: angiogenic mechanisms are blunted, reactive oxygen species accumulate, capillary function declines and eventually, capillaries disappear. This, we propose, forms the foundation of the reciprocal relationship between vascular density, blood flow, and metabolic needs and functionality of nearby cells.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"156 ","pages":"Article 107393"},"PeriodicalIF":4.0,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301753","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":"Protective effects of Salvia Haenkei extract on a model of Doxorubicin-induced cardiotoxicity","authors":"Edoardo Lazzarini ,&nbsp;Vanessa Biemmi ,&nbsp;Carolina Balbi ,&nbsp;Azucena Rendon ,&nbsp;Claudia Altomare ,&nbsp;Andrea Giori ,&nbsp;Manuel Colucci ,&nbsp;Andrea Alimonti ,&nbsp;Lucio Barile","doi":"10.1016/j.vph.2024.107327","DOIUrl":"https://doi.org/10.1016/j.vph.2024.107327","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"155 ","pages":"Article 107327"},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422970","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":"Novel NLRP3 inflammasome inhibitors INF150 and INF195 attenuate isoproterenol-induced hypertrophy in H9c2 rat cardiac myoblast","authors":"Magalì Giordano ,&nbsp;Chiara Rubeo ,&nbsp;Tommaso Angelone ,&nbsp;Giovanna Gambarotta ,&nbsp;Stefano Comità ,&nbsp;Francesco Fedele ,&nbsp;Massimo Bertinaria ,&nbsp;Pasquale Pagliaro ,&nbsp;Claudia Penna","doi":"10.1016/j.vph.2024.107321","DOIUrl":"https://doi.org/10.1016/j.vph.2024.107321","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"155 ","pages":"Article 107321"},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141423014","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":"A detailed mathematical model of the human atrial cardiomyocyte: Integration of electrophysiology and cardiomechanics","authors":"Fazeelat Mazhar ,&nbsp;Chiara Bartolucci ,&nbsp;Francesco Regazzoni ,&nbsp;Michelangelo Paci ,&nbsp;Luca Dedè ,&nbsp;Alfio Quarteroni ,&nbsp;Cristiana Corsi ,&nbsp;Stefano Severi","doi":"10.1016/j.vph.2024.107330","DOIUrl":"https://doi.org/10.1016/j.vph.2024.107330","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"155 ","pages":"Article 107330"},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141423068","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}