Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercholesterolemia is associated with an increased incidence of vascular complications. To assess the actual degree of activation of coagulation systems and vascular disorders in hypercholesterolemia, plasma levels of vascular endothelial cell markers, such as thrombomodulin (TM), tissue-type plasminogen activator, plasminogen activator inhibitor-I (PAI-I), and von Willebrand factor, were measured in 51 patients with hypercholesterolemia. We also investigated the effects of Pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on plasma lipid, lipoprotein a, and hemostatic markers. The mean plasma levels of thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA), TM, and PAI-I were significantly elevated in hypercholesterolemia. Of the hemostatic markers, only TM was significantly increased in patients with ischemic heart diseases (IHD). The mean concentration of total cholesterol and levels of TAT, FPA, PAI-I, and TM were significantly reduced after the Pravastatin treatment. The PIC/TAT ratio was significantly increased in non-IHD patients after treatment, this was not the case in IHD patients. These findings suggested the presence of a thrombogenic state and vascular endothelial cell disorders in hypercholesterolemia; such a state might well be related to hypofibrinolysis.
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PMID:Elevated plasma levels of vascular endothelial cell markers in patients with hypercholesterolemia. 826 15

The clinical benefit of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may derive from a qualitative, functional change in atherosclerotic lesions in addition to their lipid-lowering properties. We examined whether statins altered expression of the major determinants of fibrinolytic balance, plasminogen activator inhibitor-1 (PAI-1), and tissue-type plasminogen activator (tPA) in human vascular smooth muscle (SMC) and endothelial (EC) cells. Simvastatin reduced levels of PAI-1 antigen released from SMCs and ECs stimulated with platelet-derived growth factor or transforming growth factor-beta (IC(50) approximately 1 micromol/L). Levels of EC-derived tPA increased 2-fold over the same concentrations of simvastatin that inhibited release of PAI-1. Simvastatin's inhibitory effect was mimicked by C3 exoenzyme and prevented by geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate, suggesting the involvement of geranylgeranyl-modified intermediates. Decreased PAI-1 antigen was correlated with reduced mRNA transcription and activity of the PAI-1 promoter. By inhibiting expression of PAI-1 from SMCs and ECs while increasing expression of tPA from ECs, simvastatin may alter the local fibrinolytic balance within the vessel wall toward increased fibrinolytic capacity that, in turn, would reduce thrombotic risk after plaque rupture.
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PMID:HMG CoA reductase inhibitors reduce plasminogen activator inhibitor-1 expression by human vascular smooth muscle and endothelial cells. 1066 56

The family of hydroxymethylglutaryl coenzyme A reductase inhibitors, collectively known as statins, are used clinically to reduce plasma cholesterol levels. Recent reports indicate that statin therapy is associated with a reduced risk of depression, although the mechanism underlying this antidepressant effect is unknown. Evidence suggests that increasing central BDNF activity plays an important role in the treatment of major depression. In the nervous system, the proteolytic cleavage of pro-BDNF, a BDNF precursor, to BDNF through the tissue-type plasminogen activator (tPA)-plasmin pathway represents one mechanism that can regulate the action of BDNF. In vitro studies have demonstrated that statins can induce tPA and inhibit plasminogen activator inhibitor-1, the major inhibitor of tPA. It is therefore possible that statins could act through the tPA-plasminogen pathway to increase BDNF and achieve an antidepressant effect. It is suggested that statins could be of therapeutic potential for patients with major depression: especially those that have an abnormality in the tPA-plasminogen pathway or comorbidities relating to cardiovascular disease. Furthermore, BDNF dysfunction has also been implicated in several other neuropsychiatric diseases, such as Alzheimer's disease, attention-deficit hyperactivity disorder and Rett syndrome. The potential use of statins in these diseases may warrant further exploration.
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PMID:Statins may enhance the proteolytic cleavage of proBDNF: implications for the treatment of depression. 1735 Jul 66