Platelet Vessel Wall Interactions

Gines Escolar and Maribel Dfaz-Ricart Servicio de Hemoterapia y Hemostasia Hospital Clinic, IDIBAPS Universidad de Barcelona Villarroel 170 Barcelona 08036 

Platelets are contractile blood elements with a specialized task in the arrest of bleeding. The fundamental mechanisms of this specific hmction involve adhesion, aggregation, internal contraction and secretion. Furthermore, the phospholipids present in the platelet membranes play a key role in the development of coagulation mechanisms. 

Studies with blood circulating through vascular segments mounted in specially designed chambers [1] have dramatically contributed to the understanding of the specific mechanism involved in the interaction of platelets with subendothelial components (figure 1). 

Experiments can be performed with blood from normal individuals or from patients with congenital defects of platelets or plasma proteins. Blood can also be manipulated in the laboratory to remove a specific adhesive protein, and the flow conditions modified to 

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. 

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Higher hematocrit may improve platelet-vessel wall interaction... 

The pathophysiology of uremic bleeding is multifactorial. The primary mechanisms are platelet biochemical abnormalities and alterations in platelet-vessel wall interactions. 

Rao GHR, Escolar G, and White JG. (1986). l nneprine reverses the inhibitory influence of aspirin in platelet-vessel wall interactions. Throndi. Res. 44,65-74. 

Walter U, Geiger J, Haffner C, Market T, Nehls C, Silber RE, Schanzenbacher P. Platelet-vessel wall interactions, focal adhesions, and the mechanism of action of endothelial factors. Agents Action 1995 45(suppl) 255. 

Moncada, S. and Vane, J.R. (1982). The role of prostaglandins in platelet-vessel wall interactions. In Nossel, H.L. and Vogel, H.J. (eds.) Pathobiology of the Endothelial Cell pp. 252-275. (New York Academic Press)... 

Tailor A., Cooper D., and Granger D. Platelet-vessel wall interactions in the microcirculation. Microcirculation 12 275-285,2005. 

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... 

Sakariassen, K. S., Aarts, P. A. M. M., de Groot, P. G., Houdijk, W. P. M. and Sixma, J. J. (1983). A perfusion chamber developed to investigate platelet interaction in flowing blood with human vessel wall cells, their ECM, and purified components. J. Lab. Clin. Med. 102, 522-535. 

Hawiger J, Kloczewiak M, and Timmons S. (198S). Platelet receptor niedianisms for adhesive macromolecules. In Interaction of Platelets With The Vessel Wall (Oats J, Hawiger J, and Ross R eds), American Physiological Society, Bethesda, MD). 

INTERACTION OF PLATELETS WITH EXTRACELLULAR MATRICES, ISOLATED COMPONENTS OF THE VESSEL WALL OR PURIFIED PLASMA PROTEINS... 

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. 

Hemostasis is a complex sequence of interrelated events involving toe vessel wall, platelets, and the coagulation system. Following injury to the blood vessel, platelets adhere to exposed subendothelium by a process (adhesion) which involves the interaction of a plasma protein, von Willebiand factor (vWF), and a specific protein on the platelet sur ce, glycoprotein Ib (GPIb) (Fig 1). Adhesion is followed by recruitment of additional platelets which form clumps. 

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