Vascular pharmacology最新文献

{"title":"Kinome profiling: A veritable Rosetta Stone for protease-activated receptor 1 biased signaling","authors":"Rahul Rajala , Courtney T. Griffin","doi":"10.1016/j.vph.2025.107469","DOIUrl":"10.1016/j.vph.2025.107469","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107469"},"PeriodicalIF":3.5,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190635","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":"Circulating osteonectin predicts postural imbalance and cardiac dysfunction in heart failure","authors":"Firdos Ahmad ,&nbsp;Asima Karim ,&nbsp;Javaidullah Khan ,&nbsp;Rizwan Qaisar","doi":"10.1016/j.vph.2025.107468","DOIUrl":"10.1016/j.vph.2025.107468","url":null,"abstract":"<div><div>Osteonectin, a secreted glycoprotein, plays a role in muscle-wasting disease. However, its role in chronic heart failure (CHF) -induced systemic inflammation and postural control is unknown. Here we aim to assess the potential association of soluble osteonectin with cardiac dysfunction and postural imbalance in CHF. The cardiac function, physical performance, including short physical performance battery (SPPB) for balance, handgrip strength (HGS), and the levels of plasma osteonectin and c-reactive protein (CRP) were assessed in controls (<em>n</em> = 56) and CHF patients (<em>n</em> = 286) presented with ischemic and non-ischemic CHF. CHF patients exhibited significantly lower HGS and postural balance accompanied by higher cardiac contractile dysfunction. Regardless of HF etiologies, the osteonectin and CRP levels were significantly higher in CHF patients vs. controls. The osteonectin exhibited a significant inverse correlation with left ventricular ejection fraction (LVEF) in both ischemic (r² = 0.13, <em>P</em> &lt; 0.0001) and non-ischemic (r² = 0.18, P &lt; 0.0001) CHF patients. Similarly, osteonectin has shown a strong negative correlation with cumulative SPPB score in both ischemic (r² = 0.19, <em>P</em> &lt; 0.0001) and non-ischemic (r² = 0.22, <em>P</em> &lt; 0.0001) patients. Further SPPB balance-based analysis demonstrated lower LVEF and markedly elevated osteonectin and CRP (P &lt; 0.0001), particularly in patients with poor postural balance compared to those with relatively good balance. Importantly, osteonectin demonstrated significantly higher sensitivity and specificity for CHF diagnosis on ROC curve analysis. Taken together, higher osteonectin level is associated with LV dysfunction and postural imbalance irrespective of CHF etiologies. It may serve as a biomarker for physical disability and contractile dysfunction in CHF patients.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107468"},"PeriodicalIF":3.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075641","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":"Role of Xuefu Zhuyu decoction in improving pulmonary vascular remodeling by inhibiting endothelial-to-mesenchymal transition","authors":"Zuomei Zeng ,&nbsp;Xinyue Wang ,&nbsp;Hongjuan Wang ,&nbsp;Leiyu Tian ,&nbsp;Lidan Cui ,&nbsp;Jian Guo ,&nbsp;Yucai Chen","doi":"10.1016/j.vph.2025.107467","DOIUrl":"10.1016/j.vph.2025.107467","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary hypertension (PH) is a serious vascular disease characterized by pulmonary vascular remodeling. Xuefu Zhuyu decoction (XFZYD) can potentially improve pulmonary vascular remodeling; however, its mechanism requires further investigation.</div></div><div><h3>Methods</h3><div>Rat models of monocrotaline (MCT)-induced PH and chronic thromboembolic pulmonary hypertension (CTEPH) were employed to investigate whether XFZYD has the potential to improve pulmonary vascular remodeling. After 21 days of XFZYD administration, the right ventricular systolic pressure (RVSP), organ indices, and wall thickness of pulmonary arteries of the rats were measured. Considering the possibility of endothelial-to-mesenchymal transition (EndMT), the specific mechanism of XFZYD in improving pulmonary vascular remodeling was further explored. Immunofluorescence, immunohistochemistry, and western blotting were used to detect the expression of EndMT markers, transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins, hypoxia-inducible factor-1α (HIF-1α), and levels of reactive oxygen species (ROS) in the lung tissues.</div></div><div><h3>Results</h3><div>XFZYD demonstrated significant efficacy in treating PH, as evidenced by its effects in both the rat models of MCT-induced PH and CTEPH. XFZYD remarkably improved pulmonary vascular remodeling while reducing RVSP and right ventricular hypertrophy. XFZYD has the potential to improve pulmonary vascular remodeling by inhibiting EndMT in the pulmonary vasculature. The underlying mechanism may be closely associated with the inhibition of TGF-β1/Smad and HIF-1α signaling pathways and the reduction of ROS levels in lung tissue by XFZYD.</div></div><div><h3>Conclusion</h3><div>This study indicates that XFZYD may inhibit EndMT by modulating the ROS/HIF-1α/TGF-β1 signaling pathway, thereby improving pulmonary vascular remodeling. These findings provide a theoretical foundation for the clinical application of XFZYD in PH.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107467"},"PeriodicalIF":3.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081262","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":"Indobufen versus aspirin in patients with indication for antiplatelet therapy: A systematic review and meta-analysis","authors":"Deivyd Vieira Silva Cavalcante ,&nbsp;Mrinal Murali Krishna ,&nbsp;Meghna Joseph ,&nbsp;Ana Clara Felix de Farias Santos ,&nbsp;Beatriz Ximenes Mendes ,&nbsp;Nicole Asbeg ,&nbsp;Wilton Francisco Gomes","doi":"10.1016/j.vph.2025.107465","DOIUrl":"10.1016/j.vph.2025.107465","url":null,"abstract":"<div><h3>Introduction</h3><div>Aspirin is commonly recommended for individuals who have experienced stroke or myocardial infarction (MI). Indobufen, a cyclooxygenase-1 inhibitor, has been studied as a potential alternative. We conducted a meta-analysis and trial sequential analysis (TSA) to compare indobufen with aspirin in patients requiring antiplatelet therapy.</div></div><div><h3>Methods</h3><div>We searched PubMed, Scopus, and Cochrane Central for studies that compared indobufen and aspirin antiplatelet therapies. We focused on efficacy outcomes, such as composite vascular events, MI, and ischemic stroke, and safety outcomes, such as major bleeding and any bleeding. Heterogeneity was assessed using I2 statistics, and our analysis followed the PRISMA guidelines.</div></div><div><h3>Results</h3><div>The review included 5 studies with 11,943 patients (indobufen <em>n</em> = 5952, 49.84 %), three involving post-MI and two involving post-stroke patients. No significant differences were found between the groups in composite vascular events at 90 days (RR 0.84; 95 % CI 0.46–1.53; <em>p</em> = 0.560; I2 = 53 %) and 1-year (RR 1.13; 95 % CI 0.99–1.29; <em>p</em> = 0.08; I2 = 0 %). MI (RR 0.73; 95 % CI 0.43–1.22; <em>p</em> = 0.22; I2 = 0 %), ischemic stroke (RR 1.16; 95 % CI 0.99–1.37; <em>p</em> = 0.06; I2 = 0 %), and cardiovascular death (RR 1.35; 95 % CI 0.80–2.26; <em>p</em> = 0.257; I2 = 0 %) at 1-year also showed no significant differences. Major bleeding at 1 year (RR 0.73; 95 % CI 0.41–1.31; <em>p</em> = 0.297; I2 = 64 %) was comparable, but any bleeding at 1 year showed a significant difference (RR 0.65; 95 % CI 0.43–0.98; <em>p</em> = 0.03; I2 = 87 %) favoring indobufen. Subgroup analysis of RCTs showed marginally significant increased risk regarding ischemic stroke with indobufen (RR 1.18; 95 % CI 1.00–1.39; <em>p</em> = 0.05).</div></div><div><h3>Conclusion</h3><div>The efficacy and safety of antiplatelet therapy with indobufen were comparable to those of aspirin alone. Therefore, indobufen can be considered as a suitable alternative for patients who are intolerant or hypersensitive to aspirin. Nevertheless, additional trials involving larger populations are required to establish their clinical applicability.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107465"},"PeriodicalIF":3.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042498","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 lncRNA DSCR9 is modulated in pulmonary arterial hypertension endothelial cell models and is associated with alterations in the nitric oxide pathway","authors":"N. Bernardi ,&nbsp;B.F. Neep ,&nbsp;S. Garibaldi ,&nbsp;E. Bianconi ,&nbsp;J. Aman ,&nbsp;A. Llucià-Valldeperas ,&nbsp;D. Sirello ,&nbsp;G. Zoppoli ,&nbsp;F.S. de Man ,&nbsp;P. Ameri","doi":"10.1016/j.vph.2025.107464","DOIUrl":"10.1016/j.vph.2025.107464","url":null,"abstract":"<div><div>Long non-coding RNA (lncRNA) may be involved in dysfunction of pulmonary artery endothelial cells (PAEC) and, thus, in pulmonary arterial hypertension (PAH) pathobiology.</div><div>We screened the RNA expression profile of commercial human PAEC (hPAEC) exposed to increased hydrostatic pressure, and found that the lncRNA Down syndrome critical region 9 (DSCR9) was the most regulated transcript (log2FC 1.89 vs control). We confirmed by RT-qPCR that DSCR9 levels were higher in PAEC isolated from patients with idiopathic PAH (iPAH-PAEC), as well as in induced pluripotent stem cell-derived endothelial cells (iPSC-EC) from a patient with <em>BMPR2</em>-mutated PAH, than in relevant controls. Moreover, a re-analysis of the publicly available <span><span>GSE117261</span><svg><path></path></svg></span> microarray dataset revealed that DSCR9 was upregulated in the lung tissue of PAH patients. In silico simulation indicated that DSCR9 would be mainly located in the nucleus and could interact with calcium/calmodulin-dependent protein kinase II beta (<em>CAMK2B</em>) and nitric oxide synthase 3 (<em>NOS3</em>, encoding eNOS). <em>CAMK2B</em> levels resulted 3.4-fold higher (<em>p</em> &lt; 0.05) in iPAH-PAEC transfected with a DSCR9-GFP carrying plasmid than with a GFP-only-carrying one. A trend for higher <em>NOS3</em> expression was also noted. GFP immunostaining was predominantly nuclear and cytoplasmic upon DSCR9-GFP or GFP-only transfection, respectively. <em>CAMK2B</em> and <em>NOS3</em> mRNA were also higher in iPAH-PAEC than control-PAEC in basal conditions. Instead, variations in total and phosphorylated CAMK2B, eNOS, and NO synthesis were inconsistent. We conclude that DSCR9 is upregulated in PAH-related endothelial cell models and influences <em>CAMK2B</em> and <em>NOS3</em> expression. Future studies are necessary to determine whether DSCR9 affects NO availability, including in PAH.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107464"},"PeriodicalIF":3.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029653","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":"Stay connected: The myoendothelial junction proteins in vascular function and dysfunction","authors":"Giulia Querio ,&nbsp;Federica Geddo ,&nbsp;Susanna Antoniotti ,&nbsp;Saveria Femminò ,&nbsp;Maria Pia Gallo ,&nbsp;Claudia Penna ,&nbsp;Pasquale Pagliaro","doi":"10.1016/j.vph.2025.107463","DOIUrl":"10.1016/j.vph.2025.107463","url":null,"abstract":"<div><div>The appropriate regulation of peripheral vascular tone is crucial for maintaining tissue perfusion. Myoendothelial junctions (MEJs), specialized connections between endothelial cells and vascular smooth muscle cells, are primarily located in peripheral resistance vessels. Therefore, these junctions, with their key membrane proteins, play a pivotal role in the physiological control of relaxation-contraction coupling in resistance arterioles, mainly mediated through endothelium-derived hyperpolarization (EDH). This review aims to illustrate the mechanisms involved in the initiation and propagation of EDH, emphasizing the role of membrane proteins involved in its generation (TRPV4, Piezo1, ASIC1a) and propagation (connexins, Notch). Finally, we discuss relevant studies on pathological events linked to EDH dysfunction and discuss novel approaches, including the effects of natural and dietary bioactive molecules, in modulating EDH-mediated vascular tone.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107463"},"PeriodicalIF":3.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012926","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":"Elucidating emerging signaling pathways driving endothelial dysfunction in cardiovascular aging","authors":"Anna De Bartolo ,&nbsp;Tommaso Angelone ,&nbsp;Carmine Rocca","doi":"10.1016/j.vph.2025.107462","DOIUrl":"10.1016/j.vph.2025.107462","url":null,"abstract":"<div><div>The risk for developing cardiovascular diseases dramatically increases in older individuals, and aging vasculature plays a crucial role in determining their morbidity and mortality. Aging disrupts endothelial balance between vasodilators and vasoconstrictors, impairing function and promoting pathological vascular remodeling. In this Review, we discuss the impact of key and emerging molecular pathways that transduce aberrant inflammatory signals (i.e.<em>,</em> chronic low-grade inflammation-inflammaging), oxidative stress, and mitochondrial dysfunction in aging vascular compartment. We focus on the interplay between these events, which contribute to generating a vicious cycle driving the progressive alterations in vascular structure and function during cardiovascular aging. We also discuss the primary role of senescent endothelial cells and vascular smooth muscle cells, and the potential link between vascular and myeloid cells, in impairing plaque stability and promoting the progression of atherosclerosis. The aim of this summary is to provide potential novel insights into targeting these processes for therapeutic benefit.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107462"},"PeriodicalIF":3.5,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979273","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":"Interplay between CD28 and PD-1 in T cell immunotherapy","authors":"Zuhayr Jafri ,&nbsp;Jingwen Zhang ,&nbsp;Connor H. O'Meara ,&nbsp;Anthony M. Joshua ,&nbsp;Christopher R. Parish ,&nbsp;Levon M. Khachigian","doi":"10.1016/j.vph.2024.107461","DOIUrl":"10.1016/j.vph.2024.107461","url":null,"abstract":"<div><div>Immune checkpoint therapy targeting the PD-1/PD-L1 axis has revolutionised the treatment of solid tumors. However, T cell exhaustion underpins resistance to current anti-PD-1 therapies, resulting in lower response rates in cancer patients. CD28 is a T cell costimulatory receptor that can influence the PD-1 signalling pathway (and <em>vice versa</em>). CD28 signalling has the potential to counter T cell exhaustion by serving as a potential complementary response to traditional anti-PD-1 therapies. Here we discuss the interplay between PD-1 and CD28 in T cell immunotherapy and additionally how CD28 transcriptionally modulates T cell exhaustion. We also consider clinical attempts at targeting CD28; the challenges faced by past attempts and recent promising developments.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107461"},"PeriodicalIF":3.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903745","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":"Sexual dimorphism in aortic aneurysm: A review of the contributions of sex hormones and sex chromosomes","authors":"Hao-Nan Chen ,&nbsp;Yan-Ni Hu ,&nbsp;Li-Ling Ran ,&nbsp;Mi Wang ,&nbsp;Zheng Zhang","doi":"10.1016/j.vph.2024.107460","DOIUrl":"10.1016/j.vph.2024.107460","url":null,"abstract":"<div><div>Aortic aneurysm is a common cardiovascular disease. Over time, the disease damages the structural and functional integrity of the aorta, causing it to abnormally expand and potentially rupture, which can be fatal. Sex differences are evident in the disease, with men experiencing an earlier onset and higher incidence. However, women may face a worse prognosis and a higher risk of rupture. While there are some studies on the cellular and molecular mechanisms of aneurysm formation, it remains unclear how sex factors contribute to sexual dimorphism. Therefore, this review aims to summarize the role of sex in the occurrence of aortic aneurysms, offering valuable insights for disease prevention and the development of appropriate treatment options.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107460"},"PeriodicalIF":3.5,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882878","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":"Endostatin in disease modulation: From cancer to beyond","authors":"J. Anakha,&nbsp;Yenisetti Rajendra Prasad,&nbsp;Abhay H. Pande","doi":"10.1016/j.vph.2024.107459","DOIUrl":"10.1016/j.vph.2024.107459","url":null,"abstract":"<div><div>Angiogenesis plays a pivotal role in various pathological conditions, making it a key target in therapeutic development. Anti-angiogenic therapies are gaining traction for their potential in treating a range of angiogenesis-dependent diseases. Among these, endogenous angiogenesis inhibitors, particularly endostatin, have garnered significant attention for their therapeutic potential. While extensively studied for its anti-angiogenic effects in cancer, endostatin also exhibits anti-atherosclerotic and anti-fibrotic properties, broadening its therapeutic scope. Despite the successful clinical use of recombinant human endostatin in China for nearly two decades, its broader therapeutic potential remains underexplored. Thus, this review delves into the multifaceted applications of endostatin, examining its role in ocular diseases, inflammation, reproductive disorders, and tumor angiogenesis. Furthermore, it provides a comprehensive overview of its emerging roles beyond angiogenesis, particularly in the context of atherosclerosis and fibroproliferative conditions.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107459"},"PeriodicalIF":3.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873024","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}