Rac1-mediated signaling plays a central role in secretion-dependent platelet aggregation in human blood stimulated by atherosclerotic plaque
Episode von Medizin - Open Access LMU - Teil 17/22 von Ludwig-Maximilians-Universität München · 1. Januar 2010
Background: Platelet activation requires rapid remodeling of the actin cytoskeleton which is regulated by small GTP-binding proteins. By using the Rac1-specific inhibitor NSC23766, we have recently found that Rac1 is a central component of a signaling pathway that regulates dephosphorylation and activation of the actin-dynamising protein cofilin, dense and alpha granule secretion, and subsequent aggregation of thrombin-stimulated washed platelets. Objectives: To study whether NSC23766 inhibits stimulus-induced platelet secretion and aggregation in blood. Methods: Human platelet aggregation and ATP-secretion were measured in hirudin-anticoagulated blood and platelet-rich plasma (PRP) by using multiple electrode aggregometry and the Lumi-aggregometer. Platelet P-selectin expression was quantified by flow cytometry. Results: NSC23766 (300 mu M) inhibited TRAP-, collagen-, atherosclerotic plaque-, and ADP-induced platelet aggregation in blood by 95.1%, 93.4%, 92.6%, and 70%, respectively. The IC50 values for inhibition of TRAP-, collagen-, and atherosclerotic plaque-, were 50 +/- 18 mu M, 64 +/- 35 mu M, and 50 +/- 30 mu M NSC23766 (mean +/- SD, n = 3-7), respectively. In blood containing RGDS to block integrin alpha(IIb)beta(3)-mediated platelet aggregation, NSC23766 (300 mu M) completely inhibited P-selectin expression and reduced ATP-secretion after TRAP and collagen stimulation by 73% and 85%, respectively. In ADP-stimulated PRP, NSC23766 almost completely inhibited P-selectin expression, in contrast to aspirin, which was ineffective. Moreover, NSC23766 (300 mu M) decreased plaque-stimulated platelet adhesion/aggregate formation under arterial flow conditions (1500s(-1)) by 72%. Conclusions: Rac1-mediated signaling plays a central role in secretion-dependent platelet aggregation in blood stimulated by a wide array of platelet agonists including atherosclerotic plaque. By specifically inhibiting platelet secretion, the pharmacological targeting of Rac1 could be an interesting approach in the development of future antiplatelet drugs.
Weitere Episoden von „Medizin - Open Access LMU - Teil 17/22“
- 200 years Organon of Medicine - A comparative Review of its six editions (1810-1842) 1. Januar 2010
- A powerful transgenic tool for fate mapping and functional analysis of newly generated neurons 1. Januar 2010
- Air temperature and inflammatory and coagulation responses in men with coronary or pulmonary disease during the winter season 1. Januar 2010
- Ambient particulate pollution and the world-wide prevalence of asthma, rhinoconjunctivitis and eczema in children: Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC) 1. Januar 2010
- Amiloride reduces portal hypertension in rat liver cirrhosis 1. Januar 2010
- Association between exposure to radiofrequency electromagnetic fields assessed by dosimetry and acute symptoms in children and adolescents: a population based cross-sectional study 1. Januar 2010
- Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis 1. Januar 2010
- Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome 1. Januar 2010
- Deqi sensations without cutaneous sensory input: results of an RCT 1. Januar 2010
- Diagnostic indices for vertiginous diseases 1. Januar 2010
- How large are the nonspecific effects of acupuncture? A meta-analysis of randomized controlled trials 1. Januar 2010
- Impact of the indexed effective orifice area on mid-term cardiac-related mortality after aortic valve replacement 1. Januar 2010
- Increased expression of 5-hydroxytryptamine(2A/B) receptors in idiopathic pulmonary fibrosis: a rationale for therapeutic intervention 1. Januar 2010
- LEF-1 and TCF4 expression correlate inversely with survival in colorectal cancer 1. Januar 2010
- Minocycline is cytoprotective in human corneal endothelial cells and induces anti-apoptotic B-cell CLL/lymphoma 2 (Bcl-2) and X-linked inhibitor of apoptosis (XIAP) 1. Januar 2010
Über den Podcast
Die Universitätsbibliothek (UB) verfügt über ein umfangreiches Archiv an elektronischen Medien, das von Volltextsammlungen über Zeitungsarchive, Wörterbücher und Enzyklopädien bis hin zu ausführlichen Bibliographien und mehr als 1000 Datenbanken reicht. Auf iTunes U stellt die UB unter anderem…
Ähnliche Episoden
- Die beste Runde seines Lebens — und er merkte nichts davon – CoreCheck Podcast
- Was, wenn's schiefgeht? - Wie dein Kopfkino Dich von Erfolg & glücklichen Beziehungen fernhält. – Der MagickMale Podcast – mit Orlando Owen
- Atypische Weidemyopathie: Wenn Ahornsamen zur Gefahr werden – Kernkompetenz Pferd - Pferdegesundheit mit Tierärztin Dr. Veronika Klein
- #70 Ehrlichkeit, Mut, Verbundenheit - meine Werte als Wegweiser – Funkelndes Ich
- #106 Thomas Lorenz bei der #lunchbox – Lunchbox - auf eine Runde mit einem Hund und Nina Mülhens
- Geld in der Beziehung: Wie fair ist 50:50? – Money Beats
Alle Episoden von Medizin - Open Access LMU - Teil 17/22 · Mehr Bildung-Podcasts