Vascular pharmacology最新文献

{"title":"N-glycosylation signature and its relevance in cardiovascular immunometabolism","authors":"Monika Svecla ,&nbsp;Ruifang Li-Gao ,&nbsp;David Falck ,&nbsp;Fabrizia Bonacina","doi":"10.1016/j.vph.2025.107474","DOIUrl":"10.1016/j.vph.2025.107474","url":null,"abstract":"<div><div>Glycosylation is a post-translational modification in which complex, branched carbohydrates (glycans) are covalently attached to proteins or lipids. Asparagine-link protein (<em>N</em>-) glycosylation is among the most common types of glycosylation. This process is essential for many biological and cellular functions, and impaired <em>N</em>-glycosylation has been widely implicated in inflammation and cardiovascular diseases. Different technical approaches have been used to increase the coverage of the <em>N</em>-glycome, revealing a high level of complexity of glycans, regarding their structure and attachment site on a protein. In this context, new insights from genomic studies have revealed a genetic regulation of glycosylation, linking genetic variants to total plasma <em>N</em>-glycosylation and <em>N</em>-glycosylation of immunoglobulin G (IgG). In addition, RNAseq approaches have revealed a degree of transcriptional regulation for the glycoenzymes involved in glycan structure. However, our understanding of the association between cardiovascular risk and glycosylation, determined by a complex overlay of genetic and environmental factors, remains limited. Mostly, plasma <em>N</em>-glycosylation profiling in different human cohorts or experimental investigations of specific enzyme functions in models of atherosclerosis have been reported. Most of the uncovered glycosylation associations with pathological mechanisms revolve around the recruitment of inflammatory cells to the vessel wall and lipoprotein metabolism. This review aims to summarise insights from omics studies into the immune and metabolic regulation of <em>N</em>-glycosylation and its association with cardiovascular and metabolic disease risk and to provide mechanistic insights from experimental models.</div><div>The combination of emerging techniques for glycomics and glycoproteomics with already achieved omics approaches to map the transcriptomic, epigenomic, and metabolomic profile at single-cell resolution will deepen our understanding of the molecular regulation of glycosylation as well as identify novel biomarkers and targets for cardiovascular disease prevention and treatment.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"159 ","pages":"Article 107474"},"PeriodicalIF":3.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484156","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":"Cdc42 is crucial for mural cell migration, proliferation and patterning of the retinal vasculature","authors":"Alberto Álvarez-Aznar ,&nbsp;Malavika Desai ,&nbsp;Michael M. Orlich ,&nbsp;Elisa Vázquez-Liébanas ,&nbsp;Ralf H. Adams ,&nbsp;Cord Brakebusch ,&nbsp;Konstantin Gaengel","doi":"10.1016/j.vph.2025.107472","DOIUrl":"10.1016/j.vph.2025.107472","url":null,"abstract":"<div><h3>Aims</h3><div>Mural cells constitute the outer lining of blood vessels and are essential for vascular development and function. Mural cell loss or malfunction has been associated with numerous diseases including diabetic retinopathy, stroke and amyotrophic lateral sclerosis. In this work, we investigate the role of CDC42 in mural cells <em>in vivo</em>, using the developing mouse retina as a model.</div></div><div><h3>Methods</h3><div>In this study, we generated a mouse model for <em>Cdc42</em> deletion in mural cells by crossing <em>Pdgfrb-CreER</em>^<em>T2</em> mice with <em>Cdc42flox/flox</em> mice. This model (<em>Cdc42</em>^{<em>iΔMC</em>}) allowed us to investigate the role of CDC42 in pericytes and smooth muscle cells in the developing and adult retinal vasculature.</div></div><div><h3>Results</h3><div>We find that, during postnatal development, CDC42 is required in both, pericytes and smooth muscle cells to maintain proper cell morphology, mural cell coverage and distribution. During retinal angiogenesis, <em>Cdc42</em>-depleted pericytes lag behind the sprouting front and exhibit decreased proliferation. Consequently, capillaries at the sprouting front remain pericyte deprived, become dilated and are prone to increased vascular leakage. In addition, arteries and arterioles deviate from their normal growth directions and trajectory. While in the adult retina, mural cell coverage normalizes and pericytes adopt a normal morphology, smooth muscle cell morphologies remain abnormal and arteriolar branching angles are markedly reduced.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that CDC42 is required for mural cell migration and proliferation and suggest that mural cells are essential for normal morphogenesis and patterning of the developing retinal vasculature.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"159 ","pages":"Article 107472"},"PeriodicalIF":3.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459673","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":"Vasorelaxant effects of 3-methoxycatechol are not via direct activation of voltage-gated potassium channels","authors":"Rían W. Manville ,&nbsp;Samuel N. Baldwin ,&nbsp;Olivia H. Schaub ,&nbsp;Thomas A. Jepps ,&nbsp;Geoffrey W. Abbott","doi":"10.1016/j.vph.2025.107471","DOIUrl":"10.1016/j.vph.2025.107471","url":null,"abstract":"","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"159 ","pages":"Article 107471"},"PeriodicalIF":3.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400355","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":"Effects of FGF-related gene polymorphisms on cerebral infarction in patients treated with direct oral anticoagulants","authors":"Jung Sun Kim ,&nbsp;Minju Park ,&nbsp;Yoon-A Park ,&nbsp;Da Hoon Lee ,&nbsp;Seo-A Choi ,&nbsp;Eun Jeong Jang ,&nbsp;Jeong Yee ,&nbsp;Dong-Hyeok Kim ,&nbsp;Tae-Jin Song ,&nbsp;Junbeom Park ,&nbsp;Hye Sun Gwak","doi":"10.1016/j.vph.2025.107466","DOIUrl":"10.1016/j.vph.2025.107466","url":null,"abstract":"<div><h3>Background</h3><div>The development of cerebral infarction is multifactorial, including both environmental and genetic factors. This study assessed the association between fibroblast growth factor (FGF)-related gene polymorphisms and the incidence of cerebral infarction among patients on direct oral anticoagulants (DOACs).</div></div><div><h3>Methods</h3><div>Patients over 18 years old with atrial fibrillation who were receiving DOACs for cerebral infarction prevention at Ewha Womans University Mokdong Hospital and Ewha Womans University Seoul Hospital were enrolled in this analysis. Twenty-one single nucleotide polymorphisms (SNPs) from <em>FGF1</em>, <em>FGF2</em>, and <em>FGFR1</em> were examined. In multivariable logistic regression analysis, three models (Model I: demographic factors only, Model II: demographic factors and genetic factors, and Model III: genetic factors and the CHA₂DS₂-VASc score) were constructed to identify the risk factors related to cerebral infarction.</div></div><div><h3>Results</h3><div>Among the 536 candidate patients, 21 (3.9 %) experienced cerebral infarction while taking DOACs. From Model I and Model II, age ≥ 75 years and previous thromboembolic event history increased the risk of cerebral infarction. For genetic factors in Model II and III, <em>FGF1</em> rs1596776 GG, <em>FGFR1</em> rs6996321 AA, and FGFR1 rs7012413 TT genotypes were associated with a higher risk of cerebral infarction. The area under the receiver operating curve increased from 0.747 (Model I) to 0.822 (Model II) by adding genetic factors, demonstrating better model performance.</div></div><div><h3>Conclusions</h3><div>This study uncovered the association between <em>FGF</em>-related gene polymorphisms and cerebral infarction among patients with atrial fibrillation undergoing DOAC therapy.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107466"},"PeriodicalIF":3.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383397","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 role of the longevity-associated BPIFB4 gene on cardiac microvascular cells and cardiac aging","authors":"Matteo Calligaris ,&nbsp;Aneta Aleksova ,&nbsp;Alessandra Lucia Fluca ,&nbsp;Milijana Janjusevic ,&nbsp;Giada Carpi ,&nbsp;Daniele Stefanizzi ,&nbsp;Sara Carnevali ,&nbsp;Francesco Curcio ,&nbsp;Annibale Alessandro Puca ,&nbsp;Monica Cattaneo ,&nbsp;Antonio Paolo Beltrami","doi":"10.1016/j.vph.2025.107470","DOIUrl":"10.1016/j.vph.2025.107470","url":null,"abstract":"<div><div>In recent years, the role of the cardiac microvasculature in modulating the symptoms and disease progression of patients affected by cardiac pathology has been reconsidered. The term cardiac microvascular disease (CMD) describes the set of functional and/or structural alterations of the cardiac microvasculature that reduce the ability of the heart to adequately increase its coronary blood flow to keep up with increased metabolic demand. CMD is involved in the evolution of heart disease of both ischemic and non-ischemic origin as well as in cardiac aging. The primary actors involved in this process are the cells of the stromal compartment, whose nature and biology are now investigated to a new level of detail thanks to single-cell omics studies. Recent studies on the genetics of extreme longevity have identified a polymorphic haplotype variant of the BPIFB4 gene that confers prolonged life span and health span, atheroprotective advantages, and an improved immune response.</div><div>The aim of this review was to focus on the beneficial effects of the longevity-associated variant (LAV) of BPIFB4 on cardiac microvascular cell biology, providing novel and exciting mechanisms of its action directed against the development or progression of many age-related cardiovascular diseases, thus emphasizing its translational therapeutic potential.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"158 ","pages":"Article 107470"},"PeriodicalIF":3.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256683","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":"Kinome profiling: A veritable Rosetta Stone for protease-activated receptor 1 biased signaling","authors":"Rahul Rajala ,&nbsp;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}