Lipoprotein fibrinolysis

Familial lipoprotein(a) excess Lp(a) consists of 1 mol of LDL attached to 1 mol of apo(a). Apo(a) shows structural homologies to plasminogen. Premature coronary heart disease due to atherosclerosis, plus thrombosis due to inhibition of fibrinolysis. 

The antithrombotic factors produced by endothelial cells are thrombomodulin (TM) and protein S (PS), components of the vitamin K-dependent protein C (PC) anticoagulant pathway, inhibiting F-Va-F-Villa (E15) tissue plasminogen activator (tPA), responsible for fibrinolysis (N2, LI8) and the lipoprotein-associated coagulation inhibitor (LACI), which inhibits F-VIIa-TF complex and F-Xa (B51). 

D13. Donders, S. H. J., Lustermans, F. A. Th., and van Wersch, J. W. J., Low order correlations of lipoprotein(a) with other blood lipids and with coagulation and fibrinolysis parameters in hypertensive and diabetic patients. Blood Coagulation Fibrinol. 3, 249-256 (1992). 

H11. Hajjar, K. A., Gavish, D., Breslow, J. L., and Nachman, R. L., Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature (London) 339, 303-305 (1989). 

H25. Heinrich, J., Sandkamp, M., Kokott, R., Schulte, H., and Assmann, G., Relationship of lipoprotein(a) to variables of coagulation and fibrinolysis in a healthy population. Clin. Chem. (Winston-Salem, NC) 37, 1950-1954 (1991). 

H28. Hervio, L., Chapman, M. J., Thillet, J., Loyau, S., and Angles-Cano, E., Does apolipopro-tein(a) heterogeneity influence lipoprotein(a) effect on fibrinolysis. Blood 82, 392-397... 

Hey has been shown to reduce binding of tPA to its endothelial cell receptor, annexin II, in cell cultures (50). Animal studies have indicated that elevated plasma tHcy could cause acquired dysfibrinogenemia, leading to the formation of clots that are abnormally resistant to fibrinolysis (51), Elevated plasminogen activator inhibitor and tHcy in patients with acute coronary syndrome have been shown to be associated with increased risk for major adverse cardiac events (MACE) after successful percutaneous coronary intervention (PCI) and stenting (52), whereas factor V Leiden mutation and lipoprotein (a) were not. 

Dietary MUFA have been found to have several positive effects that include, in addition to lowering human LDL-cholesterol plasma levels, positive effects on lipoprotein oxidation, coagulation, and fibrinolysis (29). Low-fat, monounsaturate-rich diets reduce the susceptibility of low-density lipoproteins to peroxidation ex vivo (30). In hypercholesterolemic subjects, diets containing MUFA resulted in favorable alterations in the fatty acid composition and oxidative profile of LDL in hypercholesterolemic subjects that were characterized as an increase in lipid peroxide lag time and a decrease in lipid peroxide formation (30). In animal studies. 

Since lipid (lipoprotein) inhibit lysis, agents that lower lipid levels have a normalizing effect on decreased fibrinolysis activity due to elevated lipids. Even the removal of normal lipid content from plasma with chloroform increases lysis activity. Vasoactive agents have previously been reported61 to stimulate activator release resulting in enhanced lysis activity of short duration. 

Tibolone reduces concentrations of total cholesterol, triglycerides, and lipoprotein(a) but significantly decreases HDL cholesterol and thus may increase overall cardiovascular risk. Tibolone increases fibrinolysis parameters without significantly altering... 

A large protein family that contains extracellular domains homologous to EGF is called the EGF-domain proteins. EGF-like domains or modules are often found in many extracellular and membrane proteins (>70). They are involved in blood coagulation, fibrinolysis and the complement systems, matrix proteins, cell surface receptors, the low-density lipoprotein receptor and the developmentally important receptor. Notch. EGF-like domains may exist as multiple copies within proteins such as in the Drosophila protein Notch with 36 copies or as a single copy as in EGF itself. It can also be found in conjunction with other modules. 

Inhibits VSMC mitogens and matrix formation Stimulates endothelial cell repair Stimulates arterial endothelial cell PGI2 synthesis Facilitates metabolism of triglyceride rich lipoproteins Faciliates fibrinolysis... 

The whole lipid system in the blood may be considered as a functional unit, with the important task of transporting of fatty acids. However, little is known of the exact functions of all constituents. The data from studies on cholesterol (free and esterified), phospholipids, a- and /3-lipoproteins and total fat values, in atherosclerosis and toxemia of pregnancy, can often be compared with data on normal subjects and on women with Uncomplicated pregnancies. There are also some reactions which seem to have a close connection with the lipids, namely blood coagulation, fibrinolysis, and clearing. ... 

As research continues and as analytical methodology becomes more precise we find a higher resolution of some lipoprotein classes and better definition of their roles. One example is lipoprotein (a) (lp(a)), first described in 1963. Lipoprotein (a) is an LDL whose normal apoprotein (apo B) is linked to an additional protein, apoprotein a, via a disulfide bridge. Lipoprotein (a) interferes with normal fibrinolysis leading to an increased prevalence of blood clots, and is thought to present an especially high risk for myocardial infarction. Characteristics and functions of lipoproteins are described in Table 3. 

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