Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined if sevoflurane given before cold ischemia of intact hearts (anesthetic preconditioning, APC) affords additional protection by further improving mitochondrial energy balance and if this is abolished by a mitochondrial KATP blocker. NADH and FAD fluorescence was measured within the left ventricular wall of 5 groups of isolated guinea pig hearts: (1) hypothermia alone; (2) hypothermia+ischemia; (3) APC (4.1% sevoflurane)+cold ischemia; (4) 5-HD+cold ischemia, and (5) APC+5-HD+cold ischemia. Hearts were exposed to sevoflurane for 15 minutes followed by 15 minutes of washout at 37 degrees C before cooling, 2 hours of 27 degrees C ischemia, and 2 hours of 37 degrees C reperfusion. The KATP channel inhibitor 5-HD was perfused before and after sevoflurane. Ischemia caused a rapid increase in NADH and a decrease in FAD that waned over 2 hours. Warm reperfusion led to a decrease in NADH and an increase in FAD. APC attenuated the changes in NADH and FAD and further improved postischemic function and reduced infarct size. 5-HD blocked the cardioprotective effects of APC but not APC-induced alterations of NADH and FAD. Thus, APC improves redox balance and has additive cardioprotective effects with mild hypothermic ischemia. 5-HD blocks APC-induced cardioprotective effects but not improvements in mitochondrial bioenergetics. This suggests that mediation of protection by KATP channel opening during cold ischemia and reperfusion is downstream from the APC-induced improvement in redox state or that these changes in redox state are not attenuated by KATP channel antagonism.
J Cardiovasc Pharmacol 2005 Sep
PMID:Improved mitochondrial bioenergetics by anesthetic preconditioning during and after 2 hours of 27 degrees C ischemia in isolated hearts. 1611 32

Activation of inflammatory and coagulation pathways is important in the pathogenesis of vascular disease. There is ample evidence that extensive cross-talk between these two systems exists, whereby inflammation not only leads to activation of coagulation, but coagulation also markedly affects inflammatory activity. The main interfaces linking coagulation and inflammation are the tissue factor pathway, thrombin, the protein C system and the fibrinolytic (or plasminogen-plasmin) system. Proinflammatory cytokines and chemokines can affect all these coagulation mechanisms, and vice versa, activated coagulation proteases and physiological anticoagulants or components of the plasminogen-plasmin system can modulate inflammation by specific cell receptors. The intricate relationship between inflammation and coagulation may not only be relevant for vascular thrombotic disease but also has major consequences in the pathogenesis of microvascular failure and subsequent multiple organ failure in the setting of severe infection. This review focuses on the present understanding of the bidirectional relationship between inflammation and coagulation.
Trends Cardiovasc Med 2005 Oct
PMID:Two-way interactions between inflammation and coagulation. 1622 80

Cyclo-oxygenase (COX) 1 mediates the production of thromboxane A2 in platelets, leading to platelet aggregation and vasoconstriction. Conversely, COX2 catalyzes endothelial prostacyclin synthesis, which effectively counteracts thromboxane A2, triggering vasodilation and platelet inhibition. Selective COX2 inhibitors decrease prostacyclin production, potentially disrupting homeostasis and creating a prothrombotic state. The VIGOR study findings of increased cardiovascular risk with rofecoxib were subsequently confirmed by large meta-analyses, observational studies and recent APPROVe trial publication. The APC trial findings of increased cardiovascular risk with Celebrex (celecoxib) conflict with those in the ADAPT trial, the upcoming PreSAP publication, a case-control study by Graham et al. and prior large clinical trials, meta-analyses and observational studies of this drug. Therefore, while an adverse class effect is a possibility for COX2 inhibitors, the published data are inconsistent. Baseline cardiovascular risk in patients might contribute significantly to these findings. In light of the negative Vioxx (rofecoxib) publicity, however, COX2 inhibitors might forever remain underinvestigated. The relative selectivity of these compounds for COX2 is extremely variable, casting significant doubt on the class-effect hypothesis. Improved endothelial function has also been reported with celecoxib, leading to endothelium-dependent vasodilation, and associated decreases in C-reactive protein and LDL cholesterol. The addition of meloxicam to low-dose aspirin and heparin has improved clinical outcomes after acute coronary syndromes. These are the first studies suggesting improvement in endothelial function and reduction of inflammation with COX2 inhibition. Thus, more randomized controlled trials are needed to study the relative cardiovascular effects of different COX2 inhibitors, alone and in combination with aspirin.
Nat Clin Pract Cardiovasc Med 2005 Jun
PMID:Drug insight: cyclo-oxygenase 2 inhibitors and cardiovascular risk--where are we now? 1626 33

Combined activated protein C resistance and dilated cardiomyopathy result in a multiplicative effect on thrombosis risk. However, it is not known that whether there is an association with activated protein C resistance and dilated cardiomyopathy. We present a 18-year-old patient with dilated cardiomyopathy, who exhibited multi-chamber intracardiac thrombi on transthoracic echocardiography associated with activated protein C resistance. Our cases emphasizes that patients with cardiac thrombosis before adulthood should be screened for an underlying coagulation abnormality besides underlying cardiac disorders.
Int J Cardiovasc Imaging 2006 Feb
PMID:Multi-chamber intracardiac thrombi associated with activated protein C resistance in a patient with dilated cardiomyopathy. 1637 62

Protein C and protein S deficiencies may uncommonly be responsible for coronary arterial thrombosis. We report a young woman with recurrent acute stent thrombosis due to the deficiency of protein C and S. After coronary stenting, stent thrombosis occurred two times despite aggressive antiplatelet therapy, including aspirin, clopidogrel and glycoprotein IIb/IIIa inhibitor. This report suggests that the deficiency of protein C and S should be born in mind in a young patient with recurrent thrombotic events, and that anticoagulants in addition to antiplatelet agents considered in the presence of their deficiency.
Int J Cardiovasc Imaging
PMID:Recurrent acute stent thrombosis associated with protein C and S deficiencies. 1650 22

Pulmonary thromboendarterectomy was performed on a patient with chronic pulmonary thromboembolism showing thrombophilia. The patient was a 56-year-old female with the above condition complicated by congenital protein C deficiency. She was admitted to our hospital with severe dyspnea accompanied by right ventricular failure. A pulmonary arteriogram showed occlusion and stenosis from lobar to segmental arteries. Cardiac catheterization showed marked pulmonary hypertension. A lung perfusion scintigram revealed multiple defects in the right and left lungs. After the insertion of an inferior vena cava filter, she was operated on. Following a median sternotomy, thromboendarterectomy of the bilateral pulmonary arteries was performed using deep hypothermia and intermittent circulatory arrest. Circulatory arrest was employed in three periods totaling up to 36 minutes. After surgery, she had improvements in pulmonary hypertension and pulmonary vascular resistance. She maintained improved lung functions, and remained in the New York Heart Association functional class I for more than two years and eight months after surgery.
Jpn J Thorac Cardiovasc Surg 2006 Feb
PMID:Pulmonary thromboendarterectomy for chronic pulmonary thromboembolism in protein C deficiency. 1651 32

Atherosclerosis remains a leading cause of morbidity and mortality worldwide. In addition to the deposition of cholesterol in the arterial wall, inflammation, cell proliferation and migration play important roles in the pathogenesis of atherosclerosis. Thrombomodulin (TM) is a cell surface-expressed glycoprotein which is predominantly synthesized by vascular endothelial cells and a critical cofactor for thrombin-mediated activation of protein C. Activated protein C is best known for its natural anticoagulant and anti-inflammatory properties. Recent evidence has revealed that TM also has protein C- and thrombin-independent physiological function. This review summarizes recent investigations of TM, giving an overview on the TM unique effects on cellular proliferation, adhesion and inflammation, all of which are important steps in atherosclerosis. The current evidence of TM in the pathogenesis of atherosclerosis will be reviewed, and the associations of TM gene polymorphisms with atherosclerosis are presented. Newly emerging data of the TM in mouse atherosclerosis model demonstrates that TM potentially may have therapeutic role in atherosclerosis.
Cardiovasc Hematol Agents Med Chem 2006 Apr
PMID:The role of thrombomodulin in atherosclerosis: from bench to bedside. 1661 Oct 51

Coronary artery bypass grafting with cardiopulmonary bypass can induce systemic inflammatory response syndrome. To assess the prevalence of preoperative antithrombin and protein C deficiencies in relation to the incidence of this syndrome, antithrombin and protein C levels were measured in 130 patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. Systemic inflammatory response syndrome developed in 36 (27.7%) patients who were predominantly male, had a lower EuroSCORE, longer cardiopulmonary bypass time, higher pre-bypass temperature, and shorter activated coagulation time. Logistic regression showed that predictive factors included bypass duration and pre-bypass temperature; however, low antithrombin levels appeared to be a negative predictive factor. Antithrombin levels were < 80% in 33.8% of patients, and 11.6% had protein C levels < 80%. Postoperative antithrombin and protein C deficiencies are not uncommon in adults undergoing cardiac surgery with cardiopulmonary bypass, but detection of these deficits did not identify patients at increased risk of systemic inflammatory response syndrome.
Asian Cardiovasc Thorac Ann 2007 Jan
PMID:Antithrombin and protein C in systemic inflammatory response syndrome. 1724 21

A 6-month-old girl with a diagnosis of double-outlet right ventricle and pulmonary stenosis had a left modified Blalock-Taussig shunt. Chest computed tomography (CT) performed on postoperative day 11 showed good patency of the shunt. However, on postoperative day 16, oxygen saturation suddenly dropped below 40%, and chest CT showed thrombotic occlusion of the shunt. Urgent thrombectomy was performed successfully. Examination of coagulation factors revealed low levels of both the amount and activity of protein C (27% and 31%, respectively). Diagnosis of heterozygous hereditary protein C deficiency was made, and the patient was placed on warfarin. She is currently in good condition.
Gen Thorac Cardiovasc Surg 2008 Nov
PMID:Thrombotic occlusion of Blalock-Taussig shunt in a patient with unnoticed protein C deficiency. 1900 53

As venous thrombosis is mostly caused by disturbances in the plasma coagulation system, abnormalities of coagulation factors are mostly risk factors for venous thromboembolism (VTE). Relatively little is known about thrombophilias that predispose to arterial thromboembolism. Although some abnormalities in the fibrinolytic pathway appear to predispose to arterial thrombosis, the associations are weak and often inconsistent between studies. At present, there is not enough consistent and clinically meaningful information to include fibrinolytic parameters in a clinical thrombophilia workup. Controversy exists as to which patients and family members to test for thrombophilia. Several testing guidelines exist. Routine screening for inherited thrombophilias is not indicated in patients with VTE provoked by immobility, surgery, and malignancy, or in those with arterial thrombosis with arteriosclerosis risk factors. Heterozygous factor V Leiden (FVL) and prothrombin 20210 mutations increase the risk for recurrent VTE only slightly once anticoagulation is stopped. Therefore, decisions regarding the length of anticoagulant therapy typically are not influenced by finding one of these heterozygous mutations. The main reason to perform thrombophilia testing in a patient is to detect a strong thrombophilia (ie, antithrombin deficiency, antiphospholipid antibody syndrome, homozygous FVL, double-heterozygous FVL plus prothrombin 20210 mutation, protein C deficiency, and maybe protein S deficiency). The finding of a strong thrombophilia has several clinical consequences: it decreases the threshold to recommend long-term anticoagulation in a patient with unprovoked VTE; facilitates discussion regarding whether anticoagulant or antiplatelet therapy is the preferred empiric treatment for a patient who had an unexplained arterial, nonarteriosclerotic thromboembolic event; and leads to the consideration of testing asymptomatic female family members for the identified thrombophilia(s) so they can be counseled on their risk of thromboembolism, the use of hormonal therapies, and the potential benefit of pre- and postpartum anticoagulant therapy.
Curr Treat Options Cardiovasc Med 2009 Apr
PMID:Thrombophilia: 2009 update. 1928 24


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