Fibrin and

The high affinity LBS is involved in the interaction of plasminogen with fibrin, a2-antiplasmin, and a plasmin inhibitor called histidine-rich glycoprotein. It has been observed that plasminogen activation takes place on the surface of fibrin and that a2-antiplasmin competitively inhibits the plasminogen—fibrin interaction at the high affinity LBS. 

The actions of plasmin on both fibrin and fibrinogen have been studied extensively. Plasmin cleaves fibrin and fibrinogen into a family of fragments known as fibrinogen and fibrin (FDP-fdp) degradation products. 

In general, arterial thrombi are platelet-rich ( white clots ) and form at ruptured atherosclerotic plaques, leading to intraluminal occlusion of arteries that can result in end-organ injury (e.g., myocardial infarction, stroke). In contrast, venous thrombi consist mainly of fibrin and red blood cells ( red clots ), and usually form in low-flow veins of the limbs, producing deep vein thrombosis (DVT) the major threat to life results when lower extremity (and, occasionally, upper extremity) venous thrombi embolize via the right heart chambers into the pulmonary arteries, i.e., pulmonary embolism (PE). 

Fibrinolytic enzymes (proteases) are used to dissolve thrombus, the insoluble aggregate of fibrin and platelet including several additional cellular and molecular components of the blood. 

Enzymology of proteases in a water-phase is well known, but its alteration in a compartment is poorly understood. There are dramatical changes in reaction rates, in enzyme contractions and in enzyme sensitivity to inhibitors, which are not exactly described. In addition, besides fibrin and platelets there are several cellular and molecular components present in a thrombus compartment, where their influence on the basic fibrinolytic reactions is not known. To study this aspect of fibrinolysis is a task of the near future [4]. 

Plasmin, a serine protease (83 kDa), can degrade fibrin, and its degradation products (FDP) are soluble in the blood. Plasmin is formed from its proenzyme (zymogen, precursor), plasminogen (92 kDa), synthesized by the liver, and secreted into the blood circulation, where its concentration is 2 pM. Plasminogen is converted to plasmin by plasminogen activators (serine proteases). 

Heparin inhibits the formation of fibrin clots, inhibits the conversion of fibrinogen to fibrin, and inactivates several of the factors necessary for the clotting of blood. Heparin cannot be taken orally because it is inactivated by gastric acid in the stomach therefore, it must be given by injection. Heparin has no effect on clots that have already formed and aids only in preventing the formation of new blood clots (thrombi). The LMWHs act to inhibit clotting reactions by binding to antithrombin HI, which inhibits the synthesis of factor Xa and the formation of thrombin. 

The white thrombus is composed of platelets and fibrin and is relatively poor in erythrocytes. It forms at the site of an injury or abnormal vessel wall, particularly in areas where blood flow is rapid (arteries). 

O The cause of an acute coronary syndrome is the rupture of an atherosclerotic plaque with subsequent platelet adherence, activation, and aggregation, and the activation of the clotting cascade. Ultimately, a clot forms composed of fibrin and platelets. 

The coagulation system that generates thrombin consists of intrinsic and extrinsic pathways. Both pathways are composed of a series of enzymatic reactions eventually producing thrombin, fibrin, and a stable clot. In parallel with the coagulation, the fibrinolytic system is activated locally. Plasminogen is converted to plasmin, which dissolves the fibrin mesh1 2 3 (Fig. 64—1). 

Fibrinolysis A normal ongoing process that dissolves fibrin and results in the removal of small blood clots hydrolysis of fibrin. 

Thrombus An aggregation of fibrin and platelets within a blood vessel. A thrombus often causes vessel obstruction, inflammation, and injury. 

An abscess begins by the combined action of inflammatory cells (such as neutrophils), bacteria, fibrin, and other inflammatory components. Within the abscess, oxygen tension is low, and anaerobic bacteria thrive. 

The accumulation of apo(a) in the aorta wall and in saphenous vein bypass grafts in relation to Lp(a) levels was recently demonstrated (C14, R3). Subsequently, the preferential deposition of extracellular apo(a) in atherosclerotic lesions of aortic and coronary artery tissue, in conjunction with the intracellular localization of apo(a) in macrophage-derived foam cells, has been the focus of a number of studies (N6, P7, S34, S35, W17). These careful studies also demonstrated the avid binding of Lp(a) to extracellular matrix components and the colocalization of fibrin and apo(a) in atheromatous lesions (N8, W16). 

To explain the relationship between Lp(a) concentrations and risk of atherosclerosis, several hypothesis could be brought forward first, Lp(a) affects the metabolism of cholesterol and LDL secondly, Lp(a) plays a role in foam-cell and plaque formation thirdly, Lp(a) interacts with the activation of plasminogen to plasmin, the key step in the fibrinolytic system (L10, M27). Such activation can occur in two different localizations, i.e., on fibrin and its proteolytic residues, and on the surface of endothelial and monocytic cells. 

The effects of Lp(a) on the fibrinolytic system are based on the homology between plasminogen and Lp(a) (E3, E5, K4). Inactive Glu-plasminogen is converted to inactive glutamine-plasmin or inactive lysine-plasmin. Both can be converted to active lysine-plasmin, the activity of which is based on the serine protease part that splits fibrin and fibrinogen, but also factors V and Villa. In addition, Lp(a) is able to activate factor XII, factor VII, and the complement factors Cl and C3. 

Plasminogen can bind to fibrin and fibrinogen. This process is markedly increased by partial proteolysis of fibrin, by which more lysine residues are... 

Scanu (S9) confirmed that Lp(a) binds to fibrin and competes with plasminogen and tPA. Therefore, the activation of plasminogen is prohibited, a process involving the temairy complex of tPA, plasminogen, and fibrinogen. As a result, clot lysis in vitro is diminished (Fig. 10). 

Another theory is that the inhibition of fibrinolysis is due to the interaction of Lp(a) with tPA bound to fibrin, and thereby influencing plasminogen activation (L10, R17, R18). Von Hodenberg (H32), however did not find a relationship between Lp(a) level and treatment success of thrombolysis in acute myocardial infarction with recombinant tPA. 

Fig. 10. Scheme representing the inhibitory effect of Lp(a) on the binding of plasminogen to the surface of fibrin and on its activation by fibrin-bound tPA. [With permission of Armstrong et al. f A13).]... 

Interaction of tumor cells in circulation with fibrin and platelets,... 

The complete identification of the amino acids which are essential in the diet is due to W.C. Rose (1938). His first attempts to replace casein with its constituents were unsuccessful because an essential amino acid component in the protein hydrolysate had been missed. After threonine had been isolated by him from casein and fibrin, and shown to be essential, Rose identified val, met, his, lys, phe, leu, ile, thr, and arg as... 

The role of the fibrinolytic system is to dissolve any clots that are formed within the intact vascular system and so restrict clot formation to the site of injury. The digestion of the fibrin and hence its lysis is catalysed by the proteolytic enzyme, plasmin, another serine proteinase. Plasmin is formed from the inactive precursor, plasminogen, by the activity of yet other proteolytic enzymes, urokinase, streptokinase and tissue plasminogen activator (tPA) which are also serine proteinases. These enzymes only hydrolyse plasminogen that is bound to the fibrin. Any plasmin that escapes into the general circulation is inactivated by binding to a serpin (Box 17.2). 

The blood plasma is an aqueous solution of electrolytes, nutrients, metabolites, proteins, vitamins, trace elements, and signaling substances. The fluid phase of coagulated blood is known as blood serum. It differs from the plasma in that it lacks fibrin and other coagulation proteins (see p. 290). 

Fibronectins are typical representatives of adhesive proteins. They are filamentous dimers consisting of two related peptide chains (each with a mass of 250 kDa) linked to each other by disulfide bonds. The fibronectin molecules are divided into different domains, which bind to cell-surface receptors, collagens, fibrin, and various proteoglycans. This is what gives fibronectins their molecular glue" characteristics. 

Thrombin [EC 3.4.21.5], also known as fibrinogenase, catalyzes the hydrolysis of peptide bonds, exhibiting preferential cleavage for the Arg—Gly peptide bond. The enzyme, a member of the peptidase family SI, activates fibrinogen to fibrin and releases fibrinopeptide A and B. Thrombin, formed from prothrombin, is more selective in peptide hydrolysis than trypsin or plasmin. 

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