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)

The fibrinolytic system (the plasminogen activating system) is involved in several physiological and pathological processes. Through the transformation of plasminogen to the aggressive broad spectrum protease plasmin, potent enzymatic activity is released. Plasmin acts directly on connective tissue components, and indirectly by activating proforms of the metalloproteinases. The destructive potential of the fibrinolytic system may thus be of importance for the initiation and progression of periodontal diseases. Earlier studies have shown high concentrations of the plasminogen activator t-PA and its inhibitor PAI-2 in gingival crevicular fluid (GCF) as well as enhanced concentrations in areas of gingival inflammation. The aim of this study was to investigate a possible relationship between the gingival inflammatory reactivity and the fibrinolytic activity in gingival crevicular fluid. Thirty-one young individuals took part in the study. Gingival Index scores and Plaque Index scores were assessed and used to formulate a score expressing an individuals' inflammatory response to microbial plaque levels (Relative G/P score). The fibrinolytic activity of GCF was assessed with a fibrin gel lysis assay, and the levels of t-PA and PAI-2 were assayed with ELISAs. All samples showed fibrinolytic activity. A positive correlation between the fibrinolytic activity and Relative G/P score was found. Thus, in individuals with an enhanced reactivity to dental plaque, a higher plasminogen activating activity in GCF was seen. This indicates a higher potential for tissue proteolysis in these individuals, possibly facilitating spread and deeper involvement of the lesions.
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PMID:Relationship between fibrinolytic activity and gingival inflammatory reaction in young individuals. 1255 44

Plaque rupture and subsequent embolism as well as thrombosis are major causes of acute myocardial infarction and stroke secondary to atherosclerosis. Pai-1, t-PA, TF and ET-1 are thrombosis- and thrombolysis-related factors which play important roles in thrombosis formation and plaque rupture. Since acute myocardial infarction and stroke are more likely to occur between 6 a.m. and 12 p.m. than at another time of the day, we studied the relationship between circadian rhythm and Pai-1, t-PA, TF and ET-1 in normal and atherosclerotic mice. Atherosclerosis was developed in apoE-/- mice fed a normal diet or a high cholesterol diet. The expression of Pai-1, t-PA, TF and ET-1 in the hearts of control C57BL/6J mice and atherosclerotic mice was measured by real-time RT-PCR at different Zeitgeber times (ZT) including ZT0, ZT4, ZT8, ZT10, ZT12, ZT14, ZT16 and ZT20. The expression of Pai-1, t-PA, TF and ET-1 peaked between ZT14 and ZT16 and bottomed at ZT10 in C57BL/6J mice. Their expression in apoE-/- mice fed a normal diet lost circadian rhythm. Their expression in apoE-/- mice fed a high cholesterol diet peaked at ZT4, indicating a reverse circadian rhythm. Our result indicates that circadian changes in the expression of Pai-1, t-PA, TF and ET-1 may be involved in the onset of myocardial infarction and stroke.
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PMID:Circadian rhythm disorder of thrombosis and thrombolysis-related gene expression in apolipoprotein E knock-out mice. 1863 67

Lysophosphatidic acid (LPA) accumulates in the central atheroma of human atherosclerotic plaques and is the primary platelet-activating lipid constituent of plaques. Here, we investigated the enzymatic regulation of LPA homeostasis in atherosclerotic lesions at various stages of disease progression. Atherosclerotic lesions were induced in carotid arteries of low-density lipoprotein receptor-deficient mice by semiconstrictive collar placement. At 2-week intervals after collar placement, lipids and RNA were extracted from the vessel segments carrying the plaque. Enzymatic-and liquid chromatography-mass spectrometry-based lipid profiling revealed progressive accumulation of LPA species in atherosclerotic tissue preceded by an increase in lysophosphatidylcholine, a precursor in LPA synthesis. Plaque expression of LPA-generating enzymes cytoplasmic phospholipase A(2)IVA (cPLA(2)IVA) and calcium-independent PLA(2)VIA (iPLA(2)VIA) was gradually increased, whereas that of the LPA-hydrolyzing enzyme LPA acyltransferase alpha was quenched. Increased expression of cPLA(2)IVA and iPLA(2)VIA in advanced lesions was confirmed by immunohistochemistry. Moreover, LPA receptors 1 and 2 were 50% decreased and sevenfold upregulated, respectively. Therefore, key proteins in LPA homeostasis are increasingly dysregulated in the plaque during atherogenesis, favoring intracellular LPA production. This might at least partly explain the observed progressive accumulation of this thrombogenic proinflammatory lipid in human and mouse plaques. Thus, intervention in the enzymatic LPA production may be an attractive measure to lower intraplaque LPA content, thereby reducing plaque progression and thrombogenicity.
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PMID:Atherosclerotic lesion progression changes lysophosphatidic acid homeostasis to favor its accumulation. 2043 Oct 29