High aggregatory responses despite antiplatelet treatment is associated with an increased risk of thrombotic complications following percutaneous coronary intervention (PCI). In the present study, we investigated the relationship between platelet aggregatory responses to ADP and the release of CD40L (sCD40L): an immunomodulatory compound involved in atherothrombosis - in patients undergoing PCI. ADP-induced platelet aggregation, sCD40L and soluble P-selectin (sP-selectin) were determined before and 24 h after PCI, in samples from 52 patients receiving aspirin and thienopyridines. Platelet aggregation to ADP above the median was defined as 'high aggregation', and aggregation below the median as 'low aggregation'. Data below are medians and interquartile ranges. Patients with 'high platelet aggregability' had a significantly higher increase in both sCD40L (Delta-values: 0.78 (-0.19-3.18) vs. -0.65 (-2.10-0.00) ng/ml, P = 0.002) and sP-selectin (Delta-values: 8.0 (-2.00-16.00) vs. 4.50 (-13.00-0.50) ng/ml, P = 0.001) compared with patients with 'low platelet aggregability'. In a multivariate linear regression analysis adjusted for clinical characteristics and type of preintervention therapy, the only independent predictors of sCD40L and sP-selectin were platelet aggregation to ADP before PCI (P < 0.001) and the combination of platelet aggregation to ADP before PCI and urgency of PCI (P < 0.001). Circulating CD40L is more markedly increased after PCI in patients with high ADP-induced platelet aggregation.
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http://dx.doi.org/10.1097/MBC.0b013e328329f28c | DOI Listing |
Int J Mol Sci
February 2025
Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Microvascular ischemia, especially in the heart and kidneys, is associated with inflammation and metabolic perturbation, resulting in cellular dysfunction and end-organ failure. Heightened production of adenosine from extracellular nucleotides released in response to inflammation results in protective effects, inclusive of adaptations to hypoxia, endothelial cell nitric oxide release with the regulation of vascular tone, and inhibition of platelet aggregation. Purinergic signaling is modulated by ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1)/CD39, which is the dominant factor dictating vascular metabolism of extracellular ATP to adenosine throughout the cardiovascular tissues.
View Article and Find Full Text PDFAnn Hematol
March 2025
Pediatric hematology unit, Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt.
Background: Glanzmann's thrombasthenia (GT) is an inherited rare bleeding disorder characterized by a deficiency or functional defect in the platelet αIIbβ3 integrin. This impairs normal platelet aggregation and leads to prolonged and spontaneous mucocutaneous bleeds.
Objectives: To report disease characteristics of a GT cohort from five tertiary hospitals in Upper Egypt.
J Biol Chem
March 2025
Department of Medicine, University of Toronto, Toronto, ON, Canada; Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada; Canadian Blood Services Centre for Innovation, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada; Toronto Platelet Immunobiology Group, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. Electronic address:
Apolipoprotein A-IV (apoA-IV) is an abundant lipid-binding protein in blood plasma. We previously reported that apoA-IV, as an endogenous inhibitor, competitively binds platelet αIIbβ3 integrin from its N-terminal residues, reducing the potential risk of thrombosis. This study aims to investigate how the apoA-IV and apoA-IV mutations affect the structure and function of apoA-IV.
View Article and Find Full Text PDFJ Med Chem
March 2025
Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
TYRO3 plays a critical role in platelet aggregation as a platelet response amplifier. Selective inhibition of TYRO3 may provide therapeutic benefits for treating thrombosis and related diseases without increasing bleeding risk. We employed a structure-based approach and discovered a novel and potent TYRO3 inhibitor UNC9426 () with an excellent Ambit selectivity score ( (1.
View Article and Find Full Text PDFPathol Res Pract
March 2025
College of Technical Engineering, the Islamic University, Najaf, Iraq; College of Technical Engineering, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq; College of Technical Engineering, The Islamic University of Babylon, Babylon, Iraq.
The glycoprotein Reelin is essential for neuronal migration during embryonic development and is involved in various cellular processes. It interacts with specific lipoprotein receptors to regulate neuronal migration and synaptic plasticity. Recent research has expanded our understanding of Reelin's functions, revealing its involvement in processes such as cell proliferation, activation, migration, platelet aggregation, and vascular development.
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