Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three patients of ischemic heart disease associated with protein C deficiency are reported. Although delayed diagnosis of protein C deficiency resulted in the failure of repeated interventions, coronary artery bypass grafting performed after making the correct diagnosis has led to satisfactory mid-term results under strict anticoagulation therapy. The level of protein C should be measured more frequently in the field of ischemic heart disease and earlier diagnosis of its deficiency should be made, because measurement of protein C does not cost much.
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PMID:Ischemic heart disease associated with protein C deficiency. 1157 50

Thrombomodulin (TM) is a vascular endothelial cell (EC) receptor that is a cofactor for thrombin-mediated activation of the anticoagulant protein C. The extracellular NH(2)-terminal domain of TM has homology to C-type lectins that are involved in immune regulation. Using transgenic mice that lack this structure (TM(LeD/LeD)), we show that the lectin-like domain of TM interferes with polymorphonuclear leukocyte (PMN) adhesion to ECs by intercellular adhesion molecule 1-dependent and -independent pathways through the suppression of extracellular signal-regulated kinase (ERK)(1/2) activation. TM(LeD/LeD) mice have reduced survival after endotoxin exposure, accumulate more PMNs in their lungs, and develop larger infarcts after myocardial ischemia/reperfusion. The recombinant lectin-like domain of TM suppresses PMN adhesion to ECs, diminishes cytokine-induced increase in nuclear factor kappaB and activation of ERK(1/2), and rescues ECs from serum starvation, findings that may explain why plasma levels of soluble TM are inversely correlated with cardiovascular disease. These data suggest that TM has antiinflammatory properties in addition to its role in coagulation and fibrinolysis.
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PMID:The lectin-like domain of thrombomodulin confers protection from neutrophil-mediated tissue damage by suppressing adhesion molecule expression via nuclear factor kappaB and mitogen-activated protein kinase pathways. 1220 72

Levels of fibrinogen, von Willebrand factor, d-dimer, antithrombin III, protein C, plasminogen, and plasminogen activator inhibitor were measured in 62 men and 37 women with ischemic heart disease before and after 20-min venous occlusion. Women compared with men had higher baseline levels of fibrinogen (4.046-/+0.1785 and 3.584-/+0.1591 g/l, respectively, p=0.021), von Willebrand factor (122.1-/+9.31 and 99.5-/+6.16%, respectively, p=0.035), plasminogen activator inhibitor (4.8-/+0.31 and 2.9-/+0.27 IU/l, respectively, p=0.009). Levels of antithrombin III, protein C, and plasminogen in women were higher than in men both at baseline (108.5-/+1.65 and 100.7-/+1.60 %, p=0.001; 129.1-/+2.91 and 107.2-/+3.79%, p=0.001; 113.6-/+2.13 and 104.1-/+1.89%; p=0.001, respectively) and after venous occlusion. There were no gender differences in dynamics of parameters of hemostasis during venous occlusion. Multifactorial regression analysis showed that gender was independently (of age, duration of hypertension, smoking, body mass index, and total cholesterol level) related to only antithrombin III and protein C levels.
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PMID:[Gender differences in the state of the system of hemostasis in patients with ischemic heart disease]. 1249 45

Hyperactivity of coagulation factor VIII (fVIII) marks hypercoagulation. FVIII enhances activity of factor IX and their combination activates factor X, which is of primary importance in prothrombin transformation into thrombin, on the phospholipid membrane. The activity of fVIII was studied in 28 patients (26 women, 2 men, mean age 49.6 +/- 7.8 years) with Sneddon's syndrome (SS). SS manifests clinically similarly to primary antiphospholipid syndrome (PAS). The leading of them are ischemic disorders of cerebral circulation (IDCC) and advanced livedo present in all the examinees. Hyperactivity of fVIII was registered in 21 (75%) of 28 patients. Most of thrombosis-related symptoms occurred more frequently in patients with high than normal activity of fVIII: ischemic strokes (91% vs 57%, p > 0.05), repeated strokes (71% vs 0%, p = 0.0014), transient IDCC (76% vs 57%, p > 0.05), vascular dementia (43% vs 0%, p > 0.05), ischemic heart disease (43% vs 0%, p > 0.05), thickening of heart valves according to echocardiography (91% vs 57%, p > 0.05), peripheral venous thromboses (24% vs 0%, p > 0.05). In high fVIII activity cardiolipin antibodies occurred more rarely (24% vs 43%, p > 0.05) but lupus anticoagulant was seen more often (47% vs 14%, p > 0.05). High fVIII activity was in 8 of 12 aPL-negative patients. It is demonstrated that elevated fVIII activity is an essential mechanism of thrombosis development in SS. The cause of this enhanced activity is suggested to be special aPL in interaction with which fVIII becomes insensitive to inactivation with protein C. The activity of protein C was normal in all the cases.
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PMID:[Clotting factor VIII in Sneddon syndrome]. 1459 91

Systematic evaluations of anemia, thrombocytopenia, and coagulopathy are essential to identifying and managing their causes successfully. In all cases, clinicians should evaluate RBC measurements alongside WBC and platelet counts and WBC differentials. Multiple competing factors may coexist; certain factors affect RBCs independent of those that affect WBCs or platelets. Ideally, clinicians should examine the peripheral blood smear for morphologic features of RBCs, WBCs, and platelets that provide important clues to the cause of the patient's hematologic disorder. Thrombocytopenia arises from decreased platelet production, increased platelet destruction, or dilutional or distributional causes. Drug-induced thrombocytopenias present diagnostic challenges, because many medicines can cause thrombocytopenia and critically ill patients often receive multiple medications. If they suspect type II HIT, clinicians must promptly discontinue all heparin sources, including LMWHs, without awaiting laboratory confirmation, to avoid thrombotic sequelae. Because warfarin anticoagulation induces acquired protein C deficiency, thereby exacerbating the prothrombotic state of type II HIT, warfarin should be withheld until platelet counts increase to more than 100,000/microL and type II HIT is clearly resolving. The presence of a consumptive coagulopathy in the setting of thrombocytopenia supports a diagnosis of DIC, not TTP-HUS, and is demonstrated by decreasing serum fibrinogen levels, and increasing TTs, PTs, aPTTs, and fibrin degradation products. Increasing D-dimer, levels are the most specific DIC parameter and reflect fibrinolysis of cross-linked fibrin. Elevated PTs or a PTTs can result from the absence of factors or the presence of inhibitors. Clinicians should suspect factor inhibitors when the prolonged PT or aPTT does not correct or only partially corrects following an immediate assay of a 1:1 mix of patient and normal plasma. In addition to factor inhibitors, antiphospholipid antibodies (e.g., lupus anticoagulant) can produce a prolonged aPTT that does not correct with normal plasma but is overcome by adding excess phospholipid or platelets. Paradoxically, a tendency to thrombosis, not bleeding, accompanies lupus anticoagulants and the antiphospholipid antibody syndrome. Transfusion of red blood cells, platelets, or plasma products is sometimes warranted, but clinicians must carefully weigh potential benefits against known risks. In critically ill patients, administering RBCs can enhance oxygen delivery to tissues. Among euvolemic patients who do not have ischemic heart disease, guidelines recommend a transfusion threshold of HGB levels in the range of 6.0 to 8.0 g/dL; patients who have HGB that is at least 10.0 g/dL are unlikely to benefit from blood transfusion. The use of rHuEPO to increase erythropoiesis offers an alternative to RBC transfusion, assuming normal, responsive progenitor cells and adequate iron, folate, and cobalamin stores. Future research should examine whether clinical outcomes from rHuEPO use in critically ill patients are important and cost-effective. Because platelets play an instrumental role in primary hemostasis, platelet transfusions are often important in managing patients who are bleeding or at risk of bleeding with thrombocytopenia or impaired platelet function. Platelet transfusions carry risks, and decisions to transfuse platelets must consider clinical circumstances. Most important, platelet transfusions are generally contraindicated if the underlying disorder is TTP or type II HIT, because platelet transfusion in these settings may fuel thrombosis and worsen clinical signs and symptoms. Plasma products can correct hemostasis when bleeding arises from malfunction, consumption, or underproduction of plasma coagulation proteins. Choice of plasma product for transfusion depends on clinical circumstances. FFP is the most commonly used plasma product to correct clotting factor deficiencies, particularly coagulopathies that are attributable to multiple clotting factor deficiency states as in liver disease, DIC, or warfarin anticoagulation. PCC or rFVIIa that is administered in small volumes may provide advantages over FFP when coagulopathies require quick reversal without risk of volume overload. Factor concentrates can replace specific factor deficiencies. Recombinant FVIIa bypasses inhibitors to factors VIII and IX and vWF. Use of rFVIIa in managing hemostatic abnormalities from severe liver dysfunction; extensive surgery, trauma, or bleeding; excessive warfarin anticoagulation; and certain platelet disorders requires further study to determine optimal and cost-effective dosing regimens. Recombinant activated protein C reduces mortality from severe sepsis that is associated with organ dysfunction in adults who are at high risk for death (APACHE scores of at least 25). In severe sepsis, levels of protein C decrease, as do fibrinogen and platelet levels. Because of its anticoagulant effect, however, drotrecogin alfa may induce bleeding. Guidelines for drotrecogin alfa use must take into account bleeding risks.
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PMID:Critical issues in hematology: anemia, thrombocytopenia, coagulopathy, and blood product transfusions in critically ill patients. 1471 Jun 93

The gene currently known as SLC22A5 was already sequenced in the Human Genome project, and it was annotated as the gene of the high affinity carnitine transporter (OCTN2) in 1998. After the verification of the real function of the OCTN2 several disease related mutations of the gene have been identified, albeit the entity of the primary carnitine deficiency syndrome (OMIM 212140) was separated earlier. Besides the description of the biochemical characteristics of the transporter the present review gives a summary on the mutation spectrum and the developing phenotypes according to the literature available on the Medline and to own observations. The disease spectrum includes the involvement of the cardiac muscle and the liver primarily, however, a relatively wide phenotype variability has been observed even with the same mutations. Metabolic crisis or cardiac arrest can develop in homozygotes. Since the carnitine plays a regulatory role in the mitochondrial oxidation of the long chain fatty acids, loss of OCTN2 function lead to severe impairment of the intracellular metabolism at biochemical level, which can explain the development of a severe, even life threatening condition. The cardiac symptoms can be well influenced by carnitine administration. There are indications that cardiac manifestations can develop even in heterozygotes probably in association with the gene-dose relationship; in the laboratory of the author a heterozygous C-->T transition at the 15 np of the exon V of the OCTN2 in a patient with mild cardiomyopathy and ischemic heart disease was verified. This results in a serine 280 phenylalanine (S280F) exchange affecting thereby one of the putative protein C kinase dependent phosphorylation sites.
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PMID:[The human OCTN2 carnitine transporter and its mutations]. 1512 18

Changes in the coagulation link of hemostasis were studied in 37 patients who had undergone coronary bypass surgery using venous and arterial conduits and in 16 healthy individuals of the same age. The recordings of hemostasiograms were examined before and 14 days after surgery. Prior to coronary bypass surgery, the patients with ischemic heart disease were found to have coagulation hemostatic disorders as moderate hyperfibrinogenemia, fibrinolytic suppression, thrombinemia, and elevated D-dimer concentrations. Postoperatively, hypercoagulation substantially increased with suppressed fibrinolysis and decreased anticoagulants in the protein C system. In this connection, it is necessary to longer use anticoagulants in the postoperative period and to thoroughly monitor hemostasiogram recordings after their discontinuance.
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PMID:[Changes in coagulation hemostasis in patients after coronary bypass surgery]. 1881 Aug 30

Activated protein C (APC) is a vitamin-K dependent natural anticoagulant protein. With its function in blood clotting reaction, APC can reduce the risk of venous thrombosis to prevent ischemic disease. A number of in vivo and in vitro studies over the past few decades have revealed that APC also exerted cytoprotective effects to decrease the mortality caused by endotoxin, sepsis, and brain ischemic stroke. The direct cytoprotective role requires APC binding to the endothelial protein C receptor (EPCR) and activating protease activated receptor-1 (PAR-1). It is now believed that the beneficial characters of APC are partially independent from its anticoagulant activity, though more studies need to be done to demonstrate the exact molecular mechanism. In this review, we have linked the cytoprotective effects of APC including the anti-inflammatory and anti-apoptosis activities to myocardial ischemic injury caused by cardiac ischemia reperfusion. Specifically, we have tried to combine the potential signaling pathways initiated by APC with the well-known adaptive signaling such as AMP-activated protein kinase (AMPK), PI3K/Akt and ERK/MAPK pathways that contribute to the cardioprotection against myocardial ischemia injury. We speculate that APC protects against cardiac ischemia injury via triggering crucial cardioprotective signaling pathways, and these effects are mostly associated with its cytoprotective activity but independent on its anticoagulant activity.
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PMID:Activated protein C: a potential cardioprotective factor against ischemic injury during ischemia/reperfusion. 1995 50

Prognostication of the course of disease in patients with high risk of unfavorable outcome of ischemic heart disease (IHD) is of great importance for creation of individualized strategy of treatment. We have investigated contribution of levels of brain natriuretic peptide (BNP) and genetic factors in the risk of development of complications of atherosclerosis in patients who have had acute coronary syndrome. We started to follow 324 patients on day 10 of stable state after acute coronary syndrome (55.1% with Q-wave myocardial infarction, 18.5% with non-Q myocardial infarction, 25.5% with unstable angina, men BNP level 624.5+/-32.13 mol/ml [70.3 - 4276.6]). Duration of followup was 2 years. Baseline BNP level in patients with unfavorable outcome during followup (fatal and nonfatal myocardial infarction and stroke) was 872.47+/-91.42 compared with 592.45+/-35.97 mol/ml in patients without unfavorable outcome (p=0,001). Multifactorial Cox analysis showed that carriage of T allele of polymorphic marker (--1654) of protein C gene, elevated BNP level, symptomatic atherosclerosis of peripheral arteries, history of MI, and use of thiazide diuretics were independently associated with unfavorable outcomes (p=0.026, <0.0001, <0.0001, =0.001, =0.024, respectively). Thus genetic factors and study of BNP allow to improve prediction of unfavorable outcome after exacerbation of IHD.
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PMID:[Prognostic value of levels of brain natriuretic peptide and genetic factors in patients after acute coronary syndrome]. 2162 95

A floating thrombus in the ascending aorta is an uncommon source of embolism. We report a case in which a floating mass in the left coronary sinus of Valsalva caused intermittent left main coronary trunk occlusion, leading to myocardial ischemia and cardiogenic shock. The mass was surgically resected. Macroscopically, the aortic wall and leaflets were normal. On histologic examination the mass was found to be a thrombus. This patient had a low level of protein C; therefore, it was presumed that the thrombus was due to protein C deficiency.
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PMID:Intermittent coronary artery occlusion caused by a floating thrombus in the left coronary sinus of valsalva of a patient with a normal aorta and protein C deficiency. 2195 5


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