Platelet receptors and signaling in the dynamics of thrombus formation.

Centro Regional de Hemodonación, Universidad de Murcia, C/ Ronda de Garay s/n., Murcia, Spain.
Haematologica (Impact Factor: 5.87). 04/2009; 94(5):700-11. DOI: 10.3324/haematol.2008.003178
Source: PubMed

ABSTRACT Hemostasis and pathological thrombus formation are dynamic processes that require a co-ordinated series of events involving platelet membrane receptors, bidirectional intracellular signals, and release of platelet proteins and inflammatory substances. This review aims to summarize current knowledge in the key steps in the dynamics of thrombus formation, with special emphasis on the crucial participation of platelet receptors and signaling in this process. Initial tethering and firm adhesion of platelets to the exposed subendothelium is mediated by glycoprotein (GP) Ib/IX/V complex and collagen receptors, GP VI and alpha(2)beta(1) integrin, in the platelet surface, and by VWF and fibrillar collagen in the vascular site. Interactions between these elements are largely influenced by flow and trigger signaling events that reinforce adhesion and promote platelet activation. Thereafter, soluble agonists, ADP, thrombin, TxA(2), produced/released at the site of vascular injury act in autocrine and paracrine mode to amplify platelet activation and to recruit circulating platelets to the developing thrombus. Specific interactions of these agonists with their G-protein coupled receptors generate inside-out signaling leading to conformational activation of integrins, in particular alpha(IIb)beta(3), increasing their ligand affinity. Binding of alpha(IIb)beta(3) to its ligands, mainly fibrinogen, supports processes such as clot retraction and platelet aggregation. Stabilization of thrombi is supported by the late wave of signaling events promoted by close contact between aggregated platelets. The best known contact-dependent signaling is outside-in signaling through alphaIb beta(3), but new ones are being clarified such as those mediated by interaction of Eph receptors with ephrins, or by Sema 4D and Gas-6 binding to their receptors. Finally, newly identified mechanisms appear to control thrombus growth, including back-shifting of activated integrins and actuation of compensatory molecules such as ESAM or PECAM-1. The expanding knowledge of thrombotic disease is expected to translate into the development of new drugs to help management and prevention of thrombosis.


Available from: Maria L Lozano, Jun 03, 2015
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Son múltiples los beneficios del ejercicio físico sobre la mente y el cuerpo, y ello es conocido que está en relación con la intensidad y duración del mismo (Cook y Koltyn., 2000). Los cambios notables a nivel mental, dejando de lado la hipótesis de las endorfinas y otros mecanismos implicados (Harbach y col., 2000; Kolata., 2002) carecen de una explicación científica y por tanto, se ha planteado otro mecanismo de acción que induzca estos efectos, siendo postulado el sistema cannabinoide como participante (Gaoni y Mechoulam., 1964; Devane y cols., 1988; Matsuda y col., 1990; Munro y col., 1993) por sus diferentes efectos sobre el cuerpo humano a través no solamente de la activación de receptores específicos (CB1 y CB2), sino también por el aumento de endocannabinoides circulantes. Diversos estudios indican niveles elevados de estos compuestos durante el ejercicio físico (Dietrich y McDaniel., 2004; Keeney y col., 2008; Fuss y Gass., 2010; Garland y col., 2011), lo que puede sugerir la implicación del sistema cannabinoide.
    Sociedad Española de Ciencias Fisiológicas (ISSN: 1889-397X), Spain; 12/2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A requirement for materials used to build prosthesis in contact with blood is a good hemocompatibility. However, there is no standard method to measure it. The first interaction blood-material is the adsorption of plasma proteins which determines the adhesion and activation of platelets which in turn derives in blood clotting. This sequence shows that adhesion and activation of platelets are the key steps in the interaction blood-material. In the present report the adhesion of platelets on titanium dioxide coatings produced by anodic oxidation is evaluated in vitro (direct counting). Coatings were produced in a range of applied voltages and different heat treatments. The results show a direct relationship between roughness platelets adhesion.
    The Minerals, Metals & Materials Society (2015), USA; 03/2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this work, cell-responsive polysaccharide hydrogels were prepared by a simple procedure based on the sequential bioconjugation and crosslinking of the polysaccharide backbone with bioactive peptides and poly(ethylene glycol)-bis(thiol) (PEG-(SH)2), respectively. Using thiol-ene reactions, we successfully functionalized hyaluronic acid (HA) and carboxymethylcellulose (CMC) with short and long peptides (5-mer and 15-mer derivatives, respectively) derived from adhesive proteins of bone extracellular matrix. The resulting HA-peptide and CMC-peptide conjugates with varying degrees of substitution were then carefully characterized by 1H NMR spectroscopy to precisely control the peptide density into the hydrogels crosslinked with PEG-(SH)2. Pre-osteoblast seeded on the hydrogels with controlled identical stiffness spread in a manner that was strongly dependent on ligand density. Surprisingly, increasing the density of the adhesive peptide anchors did not result in a plateau of initial cell spreading but rather in a bell-shaped cell response which varies with the nature of both polysaccharide backbone and functional peptide. Placing the cells under optimal conditions for cell/hydrogel interaction, we showed that in HA hydrogels, the polysaccharide moiety is not solely a passive scaffold that presents the active peptides but is an active player in cell microenvironment to control and sustain cell activity.
    Biomacromolecules 01/2015; 16(3). DOI:10.1021/bm501613u · 5.79 Impact Factor