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)

Scaly skin occurs in 80-90% of patients who are hypothyroid, the pathogenesis of which is unknown. Since thyroid hormone (T3) affects growth and differentiation in other organs, we examined the effects of its absence on keratinocytes in vitro. Human neonatal foreskin keratinocytes were cultivated and second passage cells were switched to T3-depleted (-T3) medium at 50% confluence. Cells maintained in the -T3 medium demonstrated increased (1.5 fold) levels of the cross-linking enzyme transglutaminase and increased (1.5 fold) formation of cornified envelopes, when compared to keratinocytes maintained in medium containing physiologic levels (2 X 10(-9)M) of T3. Additionally, in the -T3 cultures, the level of the protease plasminogen activator (PA), an enzyme implicated in the process of shedding of cornified cells, was decreased 70-80% of that measured in +T3 media. Absence of T3 from keratinocyte culture-medium increased both the level of the enzyme responsible for cross-linking cornified envelope precursors and the rate of envelope formation in cultured cells. The decreased levels of PA observed in the -T3 cultures could result in decreased shedding of cornified cells. These alterations in the process of keratinocyte differentiation may explain the clinically observed scaliness associated with hypothyroidism in humans. The molecular mechanism by which T3 alters keratinocyte cornification is not yet known.
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PMID:Triiodothyronine alters the cornification of cultured human keratinocytes. 247 45

T(4) levels are determinant of several components of the fibrinolytic system. However, relationships between hypothyroidism and alteration of fibrinolytic capacity are not well established, and published data remain conflicting. As the impact of hypothyroidism on both degradation and synthesis of proteins may vary according to the severity of the disease, we measured fibrinolytic activity across varying states of hypothyroidism. We measured fibrinogen, D-dimers (DDI), alpha(2)-antiplasmin activity, tissue plasminogen activator antigen (t-PA Ag), plasminogen, plasminogen activator inhibitor antigen (PAI-1 Ag), and factor XII (FXII) of the coagulation. We prospectively included 76 middle-aged female subjects: 25 controls, 24 patients displaying moderate hypothyroidism (TSH, 10--50 mU/L), and 27 patients with severe hypothyroidism (TSH, >50 mU/L). Blood pressure, body mass index, smoking habits, total cholesterol as well as high and low density lipoprotein subfractions, triglyceride, fasting glycemia, and insulinemia were recorded. We found a different pattern of fibrinolytic abnormalities according to the severity of hypothyroidism. Compared with controls, patients with moderate hypothyroidism displayed a decreased fibrinolytic activity, as reflected by lower DDI levels, higher alpha(2)-antiplasmin activities, and higher levels of t-PA and PAI-1 Ag. In sharp contrast, patients with severe hypothyroidism exhibited higher DDI levels, lower alpha(2)-antiplasmin activities, and lower t-PA and PAI-1 Ag levels. These results were not accounted for by confounding factors such as age, smoking, and components of the insulin resistance syndrome. Free T(4) was significantly associated with fibrinogen, alpha(2)-antiplasmin, PAI-1 Ag, total cholesterol, and triglyceride and was negatively associated with DDI. The main hypotheses underlying the mechanisms by which thyroid status may affect the fibrinolytic system remain to be established. In conclusion, patients with moderate hypothyroidism, who were consistently shown to be at high risk for cardiovascular disease, have decreased fibrinolytic activity. Subjects with severe hypothyroidism have a tendency toward increased fibrinolytic activity, and these modifications may participate to the bleeding tendency observed in such patients.
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PMID:Components of the fibrinolytic system are differently altered in moderate and severe hypothyroidism. 1115 38

The influence of hypothyroidism on haemostasis is controversial; both hypocoagulable and hypercoagulable states have been reported. Hypothyroidism has been associated with atherosclerosis; a hypercoagulable state in addition might represent a risk factor for thromboembolic disease. The aim of the present study was to investigate the markers of endogenous coagulation and vascular endothelial cell function and to evaluate the relationship between serum lipid profile, thyroid hormones and haemostatic parameters in hypothyroid patients. We investigated various haemostatic parameters in 20 patients with hypothyroidism and compared them with 20 euthyroid controls. The relationship between serum thyroid hormones and the haemostatic parameters was examined. The plasma levels of fibrinogen, AT III and PAI-1 were significantly increased in hypothyroid patients compared with the control group, whereas factors VIII and X activity was decreased. We showed that free T3 levels correlated with factor IX activity. Free T4, FT3 and TSH did not correlate with fibrinogen, vWF, AT III, t-PA, or PAI-1. aPTT correlated inversely with t-PA activity and positively with protein C activity. Anti-Tg correlated inversely with FV. There was a positive correlation between triglycerides and protein C. Protein S correlated inversely with high density lipoprotein cholesterol. We found a hypofibrinolytic state in patients with hypothyroidism. Our results suggest that the risk of developing thrombosis and ultimately myocardial infarction via high PAI-1 levels may be increased in patients with hypothyroidism, a result in line with recent epidemiological data. However, thyroid hormones may play a role at different levels of the complex haemostatic system.
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PMID:Blood coagulation and fibrinolytic activity in hypothyroidism. 1266 86

Acute peripheral arterial occlusion may be caused by thrombosis or embolism. The objectives of therapy are to preserve limb and life by restoration of blood flow. Thrombolytic therapy has been the mainstay, but is limited by a high risk of bleeding. Surgical treatment, often required, is invasive with higher rates of morbidity and mortality. Rheolytic thrombectomy offers a percutaneous means of thrombus removal. A 62-year-old man with chronic atrial fibrillation, idiopathic dilated cardiomyopathy, and hypothyroidism presented with sudden onset of left arm pain. His medications included warfarin, digoxin, amiodarone, and synthroid. Examination revealed a harsh 3/6 systolic nonradiating murmur. The left arm was cold and weak with absent pulses. Laboratory data showed a prothrombin time (PT) of 12 sec and an international normalized ratio of 1.4. After heparinization, angiography was performed, showing a total occlusion of the brachial artery. A rheolytic thrombectomy catheter (RTC) was introduced to remove the thrombus. The RTC run time was 90 sec. Flow was restored to the vessel, but sluggish with angiographic evidence of stenosis. Intravascular ultrasound was performed, revealing a high-grade fibromuscular stenosis. Balloon angioplasty was performed, followed by intracatheter injection of alteplase restoring normal flow. Sudden arterial occlusion is a medical emergency, which can result in limb loss. RTC's have demonstrated a reduced need for thrombolytic agents and surgical intervention, thereby decreasing complications, procedural time, and resource utilization. While most reports have focused on infra-aortic thromboses, this case highlights its utility in the arm.
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PMID:Acute upper extremity arterial occlusion: a novel role for the use of rheolytic thrombectomy and intravascular ultrasound. 1614 12

Hypothyroidism causes a tendency for cardiovascular diseases. It was recently shown that thrombin-activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis and also fibrin-plasminogen interaction by the removal of lysine and arginine residues from fibrin monomers. The aim of this study was to determine the effects of overt hypothyroidism on the levels of TAFI antigen (TAFI Ag) and TAFI activity (TAFIa). Thirty-one overt primary hypothyroid patients and age- and gender-matched 25 healthy controls were enrolled in the study. Patients were treated with L-thyroxine after the collection of blood samples. Thyroid functions were reevaluated following the achievement of euthyroid status. Thrombin-activatable fibrinolysis inhibitor Ag, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1) levels were measured with the enzyme-linked immunosorbent assay (ELISA). Thrombin-activatable fibrinolysis inhibitor activity was assessed with the chromogenic assay. Thrombin-activatable fibrinolysis inhibitor Ag (1.63% + or - 0.42% vs 1.32% + or - 0.36%, P < .01) and TAFIa (14.2 + or - 4.12 vs 11.6 + or - 3.49 microg/mL, P < .05) levels were elevated in hypothyroid patient compared to controls. Plasminogen activator inhibitor 1 and t-PA levels were not significantly different between both groups. In hypothyroid patients, TAFI Ag levels were correlated with free T(4) (r = -.373, P < .05) and thyroid-stimulating hormone (TSH) levels (r = .748, P < .001). Regression analysis showed that TSH levels were predictors of TAFI Ag levels (P < .001, beta =.671, 95% confidence interval [CI]: 0.008-0.017). Following L-thyroxine treatment, TAFI Ag (1.63% + or - 0.42%, 1.34% + or - 0.33%, P < .05) and TAFIa (14.2 + or - 4.12 microg/mL, 12.0 + or - 2.77 microg/mL, P < .05) levels were significantly decreased, but t-PA and PAI-1 levels remained unchanged. This results point out that the fibrinolytic activity was decreased in hypothyroid patients, and therefore the achievement of euthyroid status is important in ameliorating the increased risk of cardiovascular disease.
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PMID:Thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and activity assay in patients with primary hypothyroidism. 1995 91

A 63-year-old white woman with a history of hypertension, hyperlipidemia, hypothyroidism, and transient ischemic attack, on Premarin, presented with a 2-week history of worsening edema and pain on the left side of the lower extremity associated with purplish discoloration and decreased temperature after a prolonged car travel. Physical examination revealed 2+ edema from the midthigh to the toes associated with purpuric discoloration. All arterial pulses were 4+. Ultrasound examination demonstrated an acute deep vein thrombus extending from the external iliac veins down throughout the visualized veins of the left calf. The patient was started on intravenous heparin and underwent venogram with subsequent thrombolysis. After 48 hours of alteplase infusion, balloon angioplasty was performed and 2 stents were placed in the left common and external iliac veins. Premarin was discontinued and she remains on oral anticoagulation with Coumadin. The patient did well clinically and a second ultrasound showed interval improvement. There is significant family history but no personal history of thrombotic events; however, thrombophilia evaluation is unremarkable.
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PMID:Acute deep vein thrombus due to May-Thurner syndrome. 2015 6