Platelet activation vessel wall interactions

Over the years. Dr. Gines Escolar, M. D., h been actively pursuing research in relation to platelet-vessel wall interactions. He has published extensively in this area. His work has made significant contributions to the understanding of platelet-vessel wall interactions. 

For pH sensors used in in-vivo applications, especially those in continuous pH monitor or implantable applications, hemocompatibility is a key area of importance [150], The interaction of plasma proteins with sensor surface will affect sensor functions. Thrombus formation on the device surface due to accelerated coagulation, promoted by protein adsorption, provided platelet adhesion and activation. In addition, variation in the blood flow rate due to vasoconstriction (constriction of a blood vessel) and sensor attachment to vessel walls, known as wall effect , can cause significant errors during blood pH monitoring [50, 126],... 

Platelet participation in normal hemostasis. The hemostatic plug is the specific response to external vessel lesion and depends on the extent of vessel wall damage, the specific interaction between endothelial cells and activated platelets, release of the contents of platelets intracellular granules in response to activation, the conjoint activity of activated factor Vll and platelet agonists, and the open conditions of blood flow. After activation, platelets also produce the external ization of membrane phosphatidylserine through the flip-flop mechanism that will support the function of the prothrombinase complex ending in thrombin generation and local clot formation. 

There are multicellular interactions that are important in inflammatory processes and in vascular remodeling. Activated platelets induce endothelial cells to secrete chemokines and to express adhesion molecules, indicating that platelets could initiate an inflammatory (Table I) response of the vessel wall. Activated platelets promote leukocyte binding to inflamed or atherosclerotic lesions (27,28). Cell adhesion molecules (CAMs) are responsible for leukocyte-endothelium interactions. It plays a crucial role in inflammation and atherogenesis. Vascular CAM-1 (VCAM-I)and intracellular CAM-1 (ICAM-I) promote monocyte recruitment to sites of injury and constitute a critical step in inflammation and in atherosclerotic plaque development. TSP-1, a matricellular protein released in abundance from activated platelets and accumulated in sites of vascular injury, induces the expression of VCAM-1 and ICAM-1 on endothelium and significantly increases the monocyte attachment (29). 

Neointimal hyperplasia involves a complex interaction between multiple growth factors that promotes VSMC migration and proliferation (8-10). Platelet aggregation and simultaneous activation of SMCs in the media immediately follow injury to the vessel wall. Within 24 hours, DNA replication in the medial SMCs can be observed in approximately four days, migration of SMC from the media to the intima becomes apparent. In the intima, proliferation of SMC occurs for several days and stops in about four weeks, even... 

Parallel-plate perfusion system have been also useful to evaluate the relative roles of purified plasma adhesive proteins or isolated components of the vessel wall. Receptors for all fiiese proteins are present in the membrane of platelets. Potentially, platelets can adhere to all of them, although this ability does not depend exclusively on the recognition of the q>ecific proteins by its receptor but also on rheological factors. In fact, there may be more one receptor for each of the adhesive proteins. Recognition by one or another receptor may also be affected by the presence of divalent cations and by the degree of platelet activation. The use of the parallel-plate perfusion chamber together with manipulation of the perfusates and variations in experimental conditions allow the detailed study of basic pathophysiological mechanisms involved in platelet-vessel interactions. 

The haemostatic process is a complex interaction involving the blood vessel wall, platelets and blood coagulation. In the important vascular component can be distinguished passive and active elements. The relative... 

Thrombosis is an often encountered consequence of atherosclerotic alterations of the vessel wall, and there can be no doubt that in its genesis, blood platelets play a predominant role (cf.55)< Platelets in turn are of considerable interest as the model of a metabolically active, contractile cell, capable of reacting to a variety of external stimuli. In the course of their activation, they display a series of morphological and biochemical alterations, in the course of which they aggregate and acquire procoagulant properties. It is of particular interest that lipids and fatty acids are known to interact with platelets and with the blood clotting system, and this again justifies the inclusion of a chapter on thrombosis in this series of articles on diet and atherosclerosis. ... 

Let us illustrate this rather complex set of interactions with an example. Endothelial cells that line the blood vessel walls produce, upon stimulation, relatively high quantities of the 15-lipoxygenase metabolites, 15(S)-HPETE and 15(S)-HETE. When polymorphonuclear leukocytes adhere to the endothelium, as it happens for example during inflammatory events, extracel-lularly released 15(S)-HPETE and 15(S)-HETE may enter the leukocytes and serve as substrates for 5-Hpoxygenase activity (Fig. 4.25). The product of this double transformation, an unstable 5,6-epoxytetraene, is then converted by epoxide hydrolases to three products, lipoxin A4, lipoxin B4 and 7-cts,ll-trans-lipoxin A4 (Fig. 4.25). Analogous transcellular interactions are thought to occur between other cell types, for example, leukocytes and epithelial cells or leukocytes and platelets. 

---