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)

Lipoprotein (a) [Lp(a)] appears to be involved in atherogenesis and in vitro studies have suggested that it may interfere with thrombolysis. In this study, Lp(a) serum levels were determined by radioimmunoassay in 124 patients with ischemic heart disease. Of these, 47 had acute myocardial infarction, 13 had unstable angina, and 64 were age-matched patients with stable angina. Of the 60 patients with acute coronary artery disease, 34 received thrombolysis and 26 did not. In addition to Lp(a), serum plasminogen, alpha 2 antiplasmin, fibrinogen, and D-dimer (cross-linked fibrin degradation products) levels were measured. These tests were repeated after 6 hours in patients with myocardial infarction and unstable angina. No significant difference was found for admission Lp(a) levels among patients with myocardial infarction (0.324 +/- 0.047 g/liter), unstable angina (0.435 +/- 0.123 g/liter) and stable angina (0.431 +/- 0.023 g/liter), between patients with myocardial infarction with or without thrombolytic treatment, nor between late and early measurements in patients with unstable angina and acute myocardial infarction. Plasminogen, alpha 2 antiplasmin and fibrinogen values decreased significantly after thrombolytic treatment. The size of this decrease correlated positively with higher Lp(a) blood levels (p less than 0.05). Patients with Lp(a) greater than 0.25 g/liter had a 66% decrease in fibrinogen and a 53% decrease in anti-plasmin, compared with 35 and 32%, respectively, in patients with Lp(a) level less than or equal to 0.25 g/liter (p less than 0.05). Plasminogen levels revealed a similar trend, with a 61% decrease for the higher values and a 45% decrease for the lower values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein (a) blood levels in unstable angina pectoris, acute myocardial infarction, and after thrombolytic therapy. 153 Dec 83

Plasminogen activator inhibitor-1 plays a major role in the fibrinolytic system as the main physiological inhibitor of both tissue-type and urinary-type plasminogen activators. The inhibitor is present in plasma in small amounts and derives mainly from endothelial cells. Positive correlations have been reported between plasma levels and different parameters, such as serum triglycerides, insulin plasma levels and body mass index. Moreover, high plasma inhibitor concentrations have been observed in different disease states, but it must be stressed that plasminogen activator inhibitor-1 behaves as an acute-phase reactant and measurement of plasma levels is not significant in the acute phase of the disease. A possible predictive value of inhibitor levels for thrombotic events such as deep vein thrombosis and ischemic heart disease has been studied. On the basis of available studies, the predictive value is not clear for venous thrombosis, whereas plasminogen activator inhibitor-1 levels can predict some coronary events, at least in subgroups of young patients with a first myocardial infarction. It remains to be established if treatments able to reduce plasma inhibitor levels lead to a decrease in the risk of thromboembolic events.
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PMID:Predictive value for thrombotic disease of plasminogen activator inhibitor-1 plasma levels. 851 17

Plasminogen activator inhibitor-1 (PAI-1) is related to insulin resistance and several components of the insulin resistance syndrome, and PAI-1 levels are elevated in subjects with non-insulin-dependent diabetes mellitus. Many Pima Indians are obese, insulin-resistant, and hyperinsulinemic, and they have high rates of diabetes but a low risk of ischemic heart disease. In contrast to whites and Asians, PAI-1 activity is similar between nondiabetic and diabetic Pima Indians. We therefore examined the association of PAI-1 with hepatic and peripheral insulin action measured using the hyperinsulinemic-euglycemic clamp. To investigate if insulin per se has any effect on PAI-1 in vivo, we also assessed the effects of endogenous (during a 75-g oral glucose load) and exogenous (during hyperinsulinemic clamp) insulin on PAI-1 antigen. Twenty-one (14 men and seven women; mean age, 26.3 +/- 4.8 years) Pima Indians underwent a 75-g oral glucose tolerance test (OGTT) and a sequential hyperinsulinemic-euglycemic clamp. Peripheral insulin action was measured as absolute glucose uptake (M value) and normalized to estimated metabolic body size (EMBS). Hepatic insulin action was measured as percent suppression of basal hepatic glucose output during hyperinsulinemia. PAI-1 antigen was determined using a two-site enzyme-linked immunosorbent assay that detects only free PAI-1. PAI-1 antigen concentrations were significantly related to body mass index ([BMI] rs = .54, P = .012), waist (rs=.52, P=.016) and thigh (rs=.63, P=.002) circumference, and fasting plasma insulin concentration (rs=.59, P=.004). PAI-1 antigen concentrations were not significantly associated with peripheral glucose uptake (M value) during either low-dose (rs= -.01, P=NS) or high-dose (rs= -.11, P=NS) insulin infusion. PAI-1 antigen was negatively correlated with basal hepatic glucose output (rs= -.57, P=.013) and percent suppression of hepatic glucose output during hyperinsulinemia (rs= -.69, P=.005). However, this relationship was largely due to the confounding effects of BMI, waist and thigh girth, fasting insulin, and 2-hour postload glucose concentrations, and was not significant when controlled for these variables (partial rs= -.30, P=NS). There was no significant relationship of PAI-1 antigen concentration with glucose storage or glucose oxidation. Despite a threefold increase in plasma insulin concentrations during the OGTT, there were no significant changes in PAI-1 antigen concentrations (median, 57, 61, 55, and 44 ng/mL at 0, 60, 120, and 180 minutes, respectively; P=NS by ANOVA). During the hyperinsulinemic clamp, mean plasma insulin concentrations at the end of low-dose (240 pmol/m2/min) and high-dose (2,400 pmol/m2/min) infusions were 1,005 and 14,230 pmol/L, respectively. However, PAI-1 antigen concentrations at the end of low-dose and high-dose insulin infusions were similar to those at baseline (median, 63, 43, and 58 ng/mL, respectively; P=NS by ANOVA). PAI-1 antigen in Pima Indians is related to several components of the insulin resistance syndrome. However, direct measurement of insulin resistance indicates that hepatic but not peripheral insulin resistance is related to PAI-1 antigen. Neither endogenous nor exogenous hyperinsulinemia for short periods had any significant effect on PAI-1 antigen concentrations. Short-term hyperinsulinemia is unlikely to be an important regulator of PAI-1 in Pima Indians. The relationship of PAI-1 antigen to hepatic insulin resistance is largely dependent on the relationship of PAI-1 to indices of obesity and fasting insulin concentrations.
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PMID:Relationship of hepatic and peripheral insulin resistance with plasminogen activator inhibitor-1 in Pima Indians. 884 79

The initial step in atherosclerosis is the rapid targeting of monocytes to the sites of inflammation and endothelial injury. Serum levels of intercellular adhesion molecule-1 were found to be increased in ischaemic heart disease patients and polymorphisms in the E-selectin gene were associated with accelerated atherosclerosis in young (age < 40 years) patients, further suggesting a role of inflammation in atherosclerosis. Cholesterol loading in macrophages was found to induce interleukin-8 expression, suggesting an association between foam cell formation and beta 2-integrin-dependent adhesion of leukocytes. Enhanced endothelium-platelet interaction induced by hypercholesterolaemia is mediated by von Willebrand factor, whereas platelet adhesion to subendothelial matrix is mediated by fibulin-fibrinogen complexes. Activated platelets mediate the homing of leukocytes by interaction with the subendothelial matrix under shear stresses that do not allow neutrophil adhesion. They may also contribute to the oxidative modification of LDL, provide a source of lipids for foam cell generation and contribute to smooth muscle cell proliferation. Oxidized LDL induces tissue factor in macrophages that also provide sites for fibrin polymerization and decreases the anticoagulant activity of endothelium by interfering with thrombomodulin expression and inactivating tissue factor pathway inhibitor. Intravascular fibrinolysis induced by tissue-type plasminogen activator or urokinase may contribute to the initiation of atherosclerosis by inducing P-selectin and platelet activating factor as well as to plaque rupture, either directly or indirectly, by activating metalloproteinases. Plasminogen activator inhibitor-1 inhibits smooth muscle cell migration and, in the presence of vitronectin, promotes the clearance of thrombin by LDL receptor-related protein at sites of endothelial injury.
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PMID:Thrombosis and atherosclerosis. 933 57

Myocardial ischemia-reperfusion (I/R) is associated with the activation of matrix metalloproteinases (MMPs) and serine proteases. We hypothesized that activation of MMPs and the serine protease plasmin contribute to early cardiac myocyte death following I/R and that broad-spectrum protease inhibition with doxycycline (DOX) preserves myocyte viability. Rats treated daily with or without DOX beginning 48 h prior to experimentation were subjected to 30 min of coronary occlusion and 2 days of reperfusion. DOX pre-treatment reduced infarct size by 37%. DOX attenuated increases in MMP-9 and plasmin levels as determined by gelatin zymography and immunoblot, respectively. Neutrophil extravasation was unaltered by DOX as assessed by myeloperoxidase (MPO) activity. To examine the contribution of MMP-9 and plasmin to myocyte injury, cultures of neonatal rat ventricular myocytes (NRVMs) were treated for 48 h with 83 kDa MMP-9 or plasminogen in the presence or absence of DOX. MMP-9 treatment did not affect myocyte viability. Plasminogen treatment led to increased plasmin activity, resulting in loss of beta1-integrin, NRVM detachment and apoptosis. DOX co-treatment inhibited plasmin activity and preserved NRVM attachment, whereas co-treatment with the broad-spectrum MMP inhibitor GM6001 had no effect. These results indicate that plasmin causes disruption of myocyte attachment and viability independently of MMP activation in vitro and that inhibition of plasmin by DOX may reduce I/R-induced myocyte death in vivo through the inhibition of plasmin.
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PMID:Reduction of myocardial infarct size by doxycycline: a role for plasmin inhibition. 1579 48

Plasminogen activator inhibitor-1 (PAI-1) is the major physiologic inhibitor of tissue-type plasminogen activator in plasma, and is elevated in a variety of clinical situations that are associated with increased risk of ischemic cardiovascular events. Recent insights into the biology of PAI-1 suggest that it is more than just an innocent bystander in the pathogenesis of ischemic heart disease. Elevated PAI-1 levels appear to increase the risk of atherothrombotic events and may also promote the progression of vascular disease. The development and testing of specific PAI-1 antagonists will enable basic and clinical investigators the opportunity to test the hypothesis that vascular PAI-1 excess promotes the development of intravascular thrombosis and atherosclerosis.
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PMID:PAI-1 and atherothrombosis. 1610 55

The objective of the study was to determine whether Plasminogen Activator Inhibitor Type 1 (PAI-1) -675 4G/5G polymorphism is associated with the response of functional plasma PAI-1 concentrations to changes in the amount and quality of dietary fat in healthy subjects. PAI-1 is the major inhibitor of fibrinolysis, and a lower level of fibrinolytic activity could be implicated in an increased risk of IHD. Fifty-nine healthy Spanish volunteers (ten 4G/4G homozygotes, twenty-eight heterozygotes 4G/5G and twenty-one 5G/5G homozygotes) consumed three diets for periods of 4 weeks each: a SFA-rich diet (38 % fat, 20 % SFA), followed by a carbohydrate-rich diet (30 % fat, 55 % carbohydrate) and a MUFA-rich diet (38 % fat, 22 % MUFA) according to a randomized crossover design. At the end of each dietary period plasma lipid and functional plasma PAI-1 concentrations were determined. Subjects carrying the 4G allele (4G/4G and 4G/5G) showed a significant decrease in PAI-1 concentrations after the MUFA diet, compared with the SFA-rich and carbohydrate-rich diets (genotype x diet interaction: P = 0.028). 5G/5G homozygotes had the lowest plasma PAI-1 concentrations compared with 4G/4G and 4G/5G subjects (genotype: P = 0.002), without any changes as a result of the amount and the quality of the dietary fat. In summary, no differences in plasma PAI-1 concentration response were found after changes in dietary fat intake in 5G/5G homozygotes, although these subjects displayed the lowest concentrations of PAI-1. On the other hand, carriers of the 4G allele are more likely to hyper-respond to the presence of MUFA in the diet because of a greater decrease in PAI-1 concentrations.
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PMID:The -675 4G/5G polymorphism at the Plasminogen Activator Inhibitor 1 (PAI-1) gene modulates plasma Plasminogen Activator Inhibitor 1 concentrations in response to dietary fat consumption. 1790 40

Plasminogen activator inhibitor-1 (PAI-1) contributes to cardiac ventricular remodeling because migration of inflammatory cells and attenuation of extracellular matrix degradation are caused by plasmin and matrix metalloproteinase. However, the roles of PAI-1 in myocardial ischemia reperfusion (I/R) injury and the following inflammatory response have not yet been well elucidated. To clarify the role of PAI-1 in myocardial I/R injury, we used a specific PAI-1 inhibitor (IMD-1622) in a rat model. The left anterior descending coronary artery was ligated and reperfusion was performed by loosening the suture after 30 minutes of arterial occlusion. A single administration of IMD-1622 (20 mg/kg) or vehicle was given intraperitoneally and then the rats were sacrificed on day 1 or day 14 after I/R. Blood pressure, echocardiograms, histopathology, and molecular examination were performed. The examinations revealed that PAI-1 inhibitor showed limited effects on cardiac dysfunction and ventricular remodeling after I/R. We conclude that the pharmacological inhibition of PAI-1 may not affect ventricular remodeling after myocardial I/R injury.
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PMID:Effects of pharmacological suppression of plasminogen activator inhibitor-1 in myocardial remodeling after ischemia reperfusion injury. 2218 14