Fibrinogen, role

In some patients with IgA nephropathy (IgAN), intraglomerular coagulation plays a role in depositing fibrinogen (235,236). IgAN patients treated with urokinase show a marked improvement in urinary protein concentration, semm creatinine, and blood urea nitrogen levels (237). 

These proteins are called acute phase proteins (or reactants) and include C-reactive protein (CRP, so-named because it reacts with the C polysaccharide of pneumococci), ai-antitrypsin, haptoglobin, aj-acid glycoprotein, and fibrinogen. The elevations of the levels of these proteins vary from as little as 50% to as much as 1000-fold in the case of CRP. Their levels are also usually elevated during chronic inflammatory states and in patients with cancer. These proteins are believed to play a role in the body s response to inflammation. For example, C-reactive protein can stimulate the classic complement pathway, and ai-antitrypsin can neutralize certain proteases released during the acute inflammatory state. CRP is used as a marker of tissue injury, infection, and inflammation, and there is considerable interest in its use as a predictor of certain types of cardiovascular conditions secondary to atherosclerosis. Interleukin-1 (IL-1), a polypeptide released from mononuclear phagocytic cells, is the principal—but not the sole—stimulator of the synthesis of the majority of acute phase reactants by hepatocytes. Additional molecules such as IL-6 are involved, and they as well as IL-1 appear to work at the level of gene transcription. 

Fibrinogen also plays a role in the blood clotting process. It serves as a precursor for fibrin, which forms the meshwork of a blood clot. Fibrinogen is synthesized in the liver. 

Additionally, attention has been focused on some factors that, operating in the hemostatic balance, have been attributed the role of risk markers of clinical events. Thus, increased plasma concentration of factor VII, fibrinogen, plasminogen activator inhibitor type 1 (PAI-1), and the already mentioned Lp(a) have been associated with the occurrence of CHD. Much work has been done on the modulation of these factors by HT (for a review see Cano and Van Baal 2001), and both similarities and differences have been found in the sparse literature on SERM action. Raloxifene and droloxifene decrease fibrinogen more actively than does HT (Walsh et al. 1998 Herrington et al. 2000). In contrast, the effective reduction demonstrated for PAI-1 with oral HT was not confirmed for raloxifene or droloxifene (Walsh et al. 1998 de Valk-de Roo et al. 1999 Herrington et al. 2000). 

Thrombin, a serine protease, cleaves fibrinogen into fibrin to create a fibrous plug and also amplifies its own production through the activation of factor XI and cofactors V and Vlll. Thrombin also plays a crucial role in the activation of platelets through the cleavage of the protease-activated receptors on the platelet surface. Antagonists of G-protein-coupled protease-activated receptor PARi have been synthesised to study the role of thrombin PARi receptor in thrombosis and vascular injury. Thrombosis is the most common cause of death in the industrialised world and, whether through venous thromboembolism, myocardial infarction or stroke, ultimately involves the inappropriate activity of... 

The presence of the tripeptide RGD sequence, and its crucial role in the cell-attachment process, were found subsequently in vitronectin [32, 133], fibrinogen [134], von Willebrand factor [134], type I collagen [135], and many other proteins present in body fluids and extracellular matrices [136],... 

Studies of the role of protein-surface interactions in blood coagulation were done by Vroman 56). The plasma proteins were adsorbed onto various hydrophilic or hydrophobic surfaces. Vroman showed that fibrinogen was an important component of the plasma protein layer adsorbed to the solid/liquid interface. 

The two-stranded a-helical coiled coil is now recognized as one of natures favorite ways of creating a dimerization motif and has been predicted to occur in a diverse group of over 200 proteins.111 This structure consists of two amphipathic, right-handed a-helices that adopt a left-handed supercoil, analogous to a two-stranded rope where the nonpolar face of each a-helix is continually adjacent to that of the other helix. 2 This structure was first postulated by Crick to explain the X-ray diffraction pattern of a-keratin in the absence of sequence information.Pl The coiled-coil dimerization motif is natures way of creating a rod-like molecule that perhaps plays only a structural role in many fibrous proteins, such as the kmef (keratin, myosin, epidermis, fibrinogen) class 3,4 and the intermediate filament proteins)5 6 ... 

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