SEARCH · PubMed Health

Results for “P-Selectin”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

6 recordsLinked to original sources

PubMed2026

Effects of semaglutide and empagliflozin on markers of endothelial function in persons with type 2 diabetes: A post hoc analysis of a randomized clinical trial.

AIMS: The endothelium maintains vascular health by regulating blood flow and protecting against inflammatory damage. In type 2 diabetes (T2DM), however, hyperglycemia, hypertension, and hyperlipidemia place a significant burden on the endothelium, potentially leading to atherosclerosis and cardiovascular disease (CVD). While semaglutide and empagliflozin have been shown to reduce CVD risk in T2DM, it remains unclear whether these benefits are mediated by improved endothelial function. This post-hoc analysis explores the effects of these agents on markers of endothelial function, i.e. the reactive hyperaemic index (RHI) and the endothelial-derived cell adhesion molecules (CAMs) E-Selectin, ICAM-1, P-Selectin, and VCAM-1. METHODS: This was a post-hoc analysis of a 32-week randomized trial evaluating the separate and combined effects of semaglutide and empagliflozin on cardio-renal organ damage. One hundred and twenty participants with type 2 diabetes, age ≥ 50 were randomized to four groups (semaglutide, empagliflozin, the combination or placebo). An increase in RHI and/or a decrease in CAMs were considered beneficial. RESULTS: RHI increased compared to baseline (0.11, 95%CI [0.008;0.21], p = 0.03) but not compared to placebo in the semaglutide group (0.11, 95%CI [-0.04;0.24], p = 0.16). There was no effect on RHI in the empagliflozin group. Compared to placebo, E-Selectin decreased significantly in the semaglutide and combination groups (-9, 95%CI [-14.1;-5.1] p < 0.01 and - 9, 95%CI [-14.3; -5.2] p < 0.01, respectively). VCAM-1 increased in the same groups, compared to placebo (12.3, 95%CI[2.8;20.8] p = 0.01 and 16.2, 95%CI [7.2;24.3], p < 0.01, respectively).P-Selectin and ICAM-1 was not significantly affected in any of the groups, compared to placebo (p ≥ 0.11 and p ≥ 0.09, respectively). CONCLUSION: Semaglutide improved endothelial function compared to baseline, but not significantly versus placebo, which likely is due to limited power. CAM responses were heterogeneous, suggesting distinct roles in endothelial dysfunction and atherosclerosis. ClinicalTrialsRegister.eu: EudraCT 2019-000781-38.

Aged↗

PubMed2025

Proteomic insights into platelet dysregulation and pathogenic mechanisms of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Undissolved thrombus blocks the pulmonary arteries in chronic thromboembolic pulmonary hypertension (CTEPH), a potentially fatal illness that raises pulmonary resistance, causes right heart failure, and even results in death. Although platelets are linked to vascular dysfunction and thrombus formation, it is yet unknown what precise proteome alterations and mechanistic roles they play in CTEPH. METHODS: We extracted platelet-rich plasma from peripheral blood and separated the plasma to obtain enriched platelet pellet (EPP). Quantitative proteomics was used to examine EPP from CTEPH patients and healthy controls using mass spectrometry. The relationship between protein levels and clinical markers of right heart function was examined. Platelet activity, morphology, and interactions with other blood components were evaluated using transmission electron microscopy, immunofluorescence, and flow cytometry. RESULTS: The proteomic investigation found that 179 proteins were differentially expressed in CTEPH patients. The analysis revealed that these proteins were involved in crucial processes such as complement and coagulation cascades, phagosome, and neutrophil extracellular trap (NET) formation. Elevated proteins, specifically NOX2, PAD4, ITGB2, and HMGB1, have been associated to platelet-neutrophil aggregates and NET formation. In addition, enhanced P-selectin expression in platelets and plasma confirmed greater platelet activation in CTEPH patients. Notably, PAD4 and NOX2 levels showed a substantial correlation with hemodynamic parameters and right heart dysfunction. MPO-DNA, a NET marker associated with P-selectin and ITGB2 expression, was discovered in higher concentrations in CTEPH patients' plasmas. CONCLUSION: Platelet aggregation and activation in CTEPH encourage the formation of NETs, which advances the disease and prolongs thrombus. Right heart insufficiency and hemodynamic markers had a strong correlation with PAD4 and NOX2 levels, indicating that these biomarkers may be employed to assess the severity and prognosis of CTEPH disease and offer a fresh approach to targeted treatment. The results highlight the need for additional study to elucidate platelet-mediated pathways and create therapies for CTEPH that target platelets.

Humans↗

PubMed2026

Tanshinone IIA impairs platelet function and thrombus formation.

BACKGROUND: Tanshinone IIA (T-IIA) is a fat-soluble active ingredient derived from the traditional Chinese medicine Danshen and possesses cardioprotective property. However, its exact role in platelet function is unknown. OBJECTIVES: This study investigated T-IIA's role in platelet aggregation, granules release, spreading, clot retraction, as well as in vivo hemostasis and thrombus formation. METHODS: Human platelets were treated with different doses of T-IIA (10, 50, and 100 μM) to measure platelet function and activation. In addition, T-IIA was administrated into wild-type mice to evaluate hemostasis and thrombus formation. RESULTS: T-IIA significantly impaired platelet aggregation, adenosine triphosphate secretion, P-selectin expression, and spreading and clot retraction dose dependently without affecting the expression profiles of αIIbβ3 and glycoprotein VI or Ibα. Administration of T-IIA significantly prolonged mice tail bleeding time and inhibited arterial and venous thrombosis. Further analysis showed that T-IIA dose dependently reduced platelet reactive oxygen species generation. Quantitative proteomic and phosphoproteimic assays analyzing T-IIA-treated vs vehicle-treated platelets after stimulation identified dysregulated phosphorylation of several proteins, which were enriched in platelet activation. Among the downregulated phosphoproteins, Rho-associated protein kinase (ROCK)1, integrin β3, and talin1 exhibited the lower fold change of phosphorylation in T-IIA-treated platelets compared with those in vehicle-treated platelets. Consistently, T-IIA treatment inhibited the phosphorylation of ROCK1, p47phox, integrin β3, and talin1 in activated platelets. CONCLUSION: T-IIA impairs platelet function and thrombosis via inhibition of several signaling pathways including ROCK1/p47phox, β3, and talin1, implying that T-IIA may represent a promising therapeutic candidate for treating thrombotic diseases.

Animals↗

PubMed2026

Nebivolol treatment improves hypertension-induced endothelial cell dysfunction by reducing TGF-β1-dependent senescence and normalizing mitochondrial indices.

OBJECTIVES: Serum from patients with hypertension (HT) causes endothelial cell (EC) damage, leading to senescence and dysfunctional phenotype. This study investigated whether serum from patients treated with the antihypertensive drugs could normalize EC activity. METHODS: This study involved 71 patients with newly diagnosed HT, who were randomly assigned to one of three groups based on the antihypertensive treatment: amlodipine, nebivolol, or perindopril. Serum samples collected before and 6 weeks after treatment were applied to ECs in vitro to assess their angiogenic activity, cellular senescence, mitochondrial metabolism, and oxidative stress. RESULTS: Results showed that exposure of ECs to serum from patients treated for 6 weeks significantly altered EC function, with varying effects among the drugs. Serum from nebivolol-treated patients produced the most consistent benefits, reducing EC proliferation and HIF-1α expression, likely due to lower levels of angiogenic factors such as angiopoietin-1, basic fibroblast growth factor (bFGF), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF). Additionally, this serum contained reduced levels of pro-inflammatory cytokines (E-selectin, P-selectin, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNFα)) and lower TGF-β1, which are linked to HT-related EC senescence. Nebivolol treatment decreased senescence biomarkers such as SA-β-Gal, 53BP1, and p16, with SA-β-Gal reduction comparable to that of TGF-β1 neutralizing antibodies. Oxidative stress was reduced, indicated by lower oxidized DNA product levels. CONCLUSIONS: Nebivolol was the most effective at reducing the factors, associated with HT induced cellular senescence of endothelium, through reducing TGF-β1.

Humans↗

PubMed2026

Design of a modified platelet immunofluorescence test to assess platelet-reactive antibody burden and its association with platelet functional exhaustion and clinical features in chronic immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet destruction and dysfunction associated with anti-platelet antibodies. This study evaluated the relationship between total anti-platelet antibody burden, measured using a modified platelet immunofluorescence test (PIFT), platelet functional responses and clinical features in chronic ITP. Thirty-one patients with chronic ITP and 20 healthy controls were included. Bleeding severity was assessed, and platelet function was analysed in peripheral blood by measuring P-selectin expression, PAC-1 binding (antibody against active conformation of GPIIb/IIIa) and reactive oxygen species (ROS) generation at baseline and following agonist stimulation. Relative platelet-reactive antibody burden was assessed using a ratio-based PIFT assay. ITP patients demonstrated significantly higher antibody burden compared with controls. Increased platelet-reactive immunoglobulin G (IgG) signals were associated with reduced platelet responsiveness to agonist stimulation. Antibody burden correlated with bleeding severity (p < 0.01) but not with platelet count. Non-responders exhibited significantly higher antibody levels than responders. receiver operator characteristic (ROC) analysis demonstrated discrimination between responder groups at a PIFT cut-off ≥3.85 (area under the curve [AUC] 0.877, sensitivity 80%; specificity 87%). Patients above this threshold showed attenuated platelet functional responses. Taken together, this study concluded that quantitative assessment of total antibody burden against platelets using modified PIFT is associated with platelet dysfunction, bleeding severity and treatment response status in chronic ITP.

Humans↗

PubMed2026

Targeted proteomics of extreme vascular phenotypes in type 1 diabetes: the ESCAPER study.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Type 1 Diabetes (T1D), but a subset of individuals remains free from macrovascular or renal complications despite decades of hyperglycaemia and a significant risk factor burden. We used a targeted proteomic approach (Olink Cardiovascular panel III, targeting 92 proteins) to characterize the proteomic profile of cardiovascular resilience in T1D by comparing 92 patients with long-standing T1D (age 59.8 [53.2, 69.1], duration 40.0 [35.0, 45.2] years) free from macrovascular complications or nephropathy against a reference group of 57 T1D patients with accelerated vascular pathology (age 42.0 [32.0, 56.0], duration 22.0 [18.0, 27.0] years), proliferative retinopathy and/or nephropathy in relation to diabetes duration, termed Rapid Progressors (RP). Twenty proteins differed significantly between RP and Escapers (False Discovery Rate [FDR] < 0.05) after adjustment for age, sex, HbA1c, and eGFR: Caspase-3 was significantly higher in RP (Adjusted difference: + 2.12 Normalized Protein eXpression [NPX], p < 0.001). Proteins associated with platelet activation and leukocyte adhesion with increased levels in RP included Junctional Adhesion Molecule A (+ 1.40 NPX), Glycoprotein VI (GP6: + 1.29 NPX), and P-Selectin (+ 0.82 NPX) (all p < 0.001). PECAM-1 (+ 0.55 NPX) and TNFRSF14 (+ 0.43 NPX), were also elevated. RP also showed higher levels of metabolic and tissue-remodelling proteins; Transferrin Receptor (+ 0.53 NPX) and Fatty Acid Binding Protein 4 (+ 0.52 NPX), as well as higher Bleomycin Hydrolase, Trefoil Factor 3, GDF-15, U-PAR, and Cystatin B. Conversely, von Willebrand Factor (vWF) levels (- 1.35 NPX, p < 0.001) and Paraoxonase 3 (PON3) was lower in RP (- 0.34 NPX, p = 0.003). In conclusion, escaping complications in long-term T1D appears to be associated with active molecular mechanisms. Progression is marked by apoptosis (Caspase-3), fibrosis (CHI3L1) and platelet activation (GP6), whereas resilience is associated with a distinct signature involving higher vWF and PON3. These findings highlight a profound biological divergence between extreme T1D phenotypes and provide a foundation for further research into vascular resilience.

Humans↗

Results for “P-Selectin”

Effects of semaglutide and empagliflozin on markers of endothelial function in persons with type 2 diabetes: A post hoc analysis of a randomized clinical trial.

Proteomic insights into platelet dysregulation and pathogenic mechanisms of chronic thromboembolic pulmonary hypertension.

Tanshinone IIA impairs platelet function and thrombus formation.

Nebivolol treatment improves hypertension-induced endothelial cell dysfunction by reducing TGF-&#x3b2;1-dependent senescence and normalizing mitochondrial indices.

Design of a modified platelet immunofluorescence test to assess platelet-reactive antibody burden and its association with platelet functional exhaustion and clinical features in chronic immune thrombocytopenia.

Targeted proteomics of extreme vascular phenotypes in type 1 diabetes: the ESCAPER study.

Nebivolol treatment improves hypertension-induced endothelial cell dysfunction by reducing TGF-β1-dependent senescence and normalizing mitochondrial indices.