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)

Coronary artery bypass grafting (CABG) surgery impairs platelet function and reactivity to a considerable extent. However, variability in the individual patients' responses makes any generalised statement uncertain. The observed variability is nowadays thought to relate to platelet glycoprotein polymorphisms. Our objective was to investigate the association between platelet reactivity and the restoration of platelet functional response to agonists during the period following cardiosurgical operation and some genetic polymorphisms of selected platelet membrane glycoproteins. Platelet reactivity was monitored in 32 IHD patients (56 +/- 8 years) subjected to CABG surgery by means of whole blood impedance aggregometry and concurrently using the platelet function analyser (PFA-100 at four time intervals: prior to operation (A), 2 h after administration of protamine sulfate (B), 3 days after (C) and 7 days after CABG surgery (D). Three important findings were made. First, in all patients platelet reactivity became decreased 2 h postoperatively (aggregation with 20 microM ADP reduced by up to 49%, P < 0.02) and vastly increased 7 days after CABG surgery (CT(CADP) reduced down to 87% of initial value, P < 0.05, ADP-induced aggregation enhanced up to 167%, P < 0.001, and that with collagen up to 131% of the initial value, P < 0.01). Second, the frequencies of the 'prothrombotic' phenotype variants of platelet membrane glycoproteins were higher in patients referred to as the carriers of more reactive platelets compared to those with less reactive platelets (GPIa (807)T-positive, 50 vs. 28%; GPIIIa Pl(A2)-positive, 27 vs. 21%; GPIb Met(145)-positive and GPIb VNTR B-positive, 13 vs. 0%. Lastly, the restoration in platelet hyperreactivity in CABG surgery patients was recorded more often in patients who underwent postoperative myocardial ischaemic episode(s), and was associated with significantly higher frequency of the 'prothrombotic' allele (807)T of the collagen receptor glycoprotein Ia (GPIa) in these subjects (83 vs. 61%). In conclusion, in patients with ischaemic episodes after CABG, we demonstrated a fast postoperative restoration of haemostatic capacity and evidence of platelet hyperreactivity at 7 days after CABG surgery. The platelet hyperfunction seems to relate to the occurrence of platelet glycoprotein polymorphisms GPIa(807)C/T and GPIIIa PlA(1/A2) and may be important in predicting postoperative vascular complications in CABG patients.
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PMID:Platelet hyperreactivity after coronary artery bypass grafting: the possible relevance to glycoprotein polymorphisms. A preliminary report. 1145 59

It is necessary to study the membrane receptors of platelets to understand the mechanism of their aggregation for effective treatment of patients with ischemic heart disease (IHD). The aim of this paper is to estimate the significance of carbohydrate residues of the glycoprotein receptors of platelet membranes and thrombogenesis in patients with unstable angina (UA). A total of 142 patients with UA and 20 healthy individuals were examined. The carbohydrate structure of platelet membranes was studied using lectins. Lectin-dependent platelet aggregation in patients with US was found to be associated with the activation of intracellular systems and to be fibrinogen/GP IIb/IIIa-dependent. The patients with US had elevated levels of fusoco-, N-acetyl-D-galactosamine-, and mannosamine-specific carbohydrate residues onto the platelet membrane surface. Higher platelet capacity for agglutination and aggregation by altering the carbohydrate specificity of GP IIb/IIIa receptors may be one of the causes of thrombogenesis in patients with US.
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PMID:[Lectin-dependent platelet aggregation and agglutination in patients with unstable angina]. 1192 22

Platelets have a central function in haemostasis. They also participate in arterial thrombus formation in vascular disorders. Platelets have an important role in initiating and mediating ischaemia and related complications of ischemic heart disease. Several research groups are thus studying platelet activation and developing new platelet inhibitors. Platelet function is dependent upon membrane receptors and their interaction with other proteins. Binding of fibrinogen to the platelet glycoprotein (GP) IIb/IIIa receptor is a prerequisite for platelet aggregation and thrombus formation. Thus, several GPIIb/IIIa inhibitors have been developed of which abciximab is the clinically most widely used. Pigs are often used for experimental studies. We have developed a flow cytometry assay for measuring porcine platelet activation utilising an FITC-labelled chicken anti-fibrinogen antibody. ADP, ristocetin and thrombin induce fibrinogen binding to porcine platelets similarly to human platelets. Ristocetin induces platelet aggregation and microvesicle formation from porcine platelets as well as from human platelets.
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PMID:Studies of fibrinogen binding to porcine platelets by flow cytometry: a method for studies of porcine platelet activation. 1218 Apr 97

Vascular endothelial growth factor (VEGF) is a glycoprotein with a molecular weight of about 45,000 and it is an endothelial cell specific mitogen. The essential function of VEGF is induction of angiogenesis and stimulation of endothelial proliferation. Since few years there are some clinical trials using VEGF in the field of: stimulation of reendothelialization and prevention of restenosis after revascularization, therapy of peripheral vascular disorders leading to ischemic limb, therapy of ischemic heart disease through neoangiogenesis. First group of mentioned studies is making use of ability of VEGF to stimulate the endothelial proliferation and accelerate its regeneration. Second and third group of clinical trials is taking advantage of angiogenic activity of VEGF, which leads to collateral vessel development and enhancement of ischemic area perfusion. There are also studies in the field of VEGF gene therapy, which had a big advantage over treatment with VEGF-protein because it is stimulating VEGF production for even few weeks. Besides there are new ways of drug administration. The specialist of many different medicine disciplines (not only of cardiovascular diseases) are interested in VEGF. The results of their studies are pointing at purposefulness of continuing them and making that VEGF is having bigger and bigger importance in medicine.
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PMID:[Vascular endothelial growth factor and its application in therapy of cardiovascular diseases]. 1236 14

This study examines the safety and efficacy of low molecular weight heparin (LMWH) in combination with platelet glycoprotein (GP) IIb/IIIa inhibitors in patients with acute myocardial infarction (AMI). LMWH has been shown to be as effective as unfractionated heparin (UFH) in the treatment of acute coronary syndrome (ACS), but there are limited data regarding the safety and efficacy of LMWH in combination with GP IIb/IIIa inhibitors. We studied 37,320 patients in the National Registry of Myocardial Infarction 3 who were treated with GP IIb/IIIa receptor antagonists from April 1998 to September 2000. Using univariate analysis, clinical events were compared between 2,482 patients who received LMWH and 34,838 patients who were treated with UFH. To adjust for confounding covariates, a multivariate regression analysis was also performed. Major bleeding rates were 4.0% in patients on LMWH versus 4.2% in patients who were treated with UFH (odds ratio [OR] 0.99, 95% confidence interval [CI] 0.80 to 1.23, p = 0.92). Similarly, there was no significant difference in the occurrence of recurrent myocardial ischemia (OR 0.93, 95% CI 0.82 to 1.06, p = 0.26), and in-hospital death (OR 0.86, 95% CI 0.71 to 1.05, p = 0.14) between groups. There was a trend toward a decreased risk of recurrent AMI in patients who received LMWH compared with those on UFH (1.5% vs 1.9%, OR 0.74, 95% CI 0.53 to 1.05, p = 0.09). LMWH appears to be a safe and effective alternative to UFH in patients with AMI who receive IIb/IIIa inhibitors.
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PMID:Safety and effectiveness of combined low molecular weight heparin and glycoprotein IIb/IIIa inhibitors. 1239 53

Myocardial ischaemia activates blood platelets and cardiac sympathetic afferents, which mediate chest pain and cardiovascular reflex responses. We have demonstrated that activated platelets stimulate ischaemically sensitive cardiac sympathetic afferents. Platelets absorb and release 5-hydroxytryptamine (5-HT) when they are activated. In the present study we hypothesized that, by releasing 5-HT, activated platelets stimulate cardiac afferents during ischaemia through a 5-HT(3) receptor mechanism. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were obtained from cats. Activation of platelets in PRP was induced by thrombin (5 units ml(-1)) or collagen (2 mg kg(-1)). Using high-performance liquid chromatography, we observed that the concentration of 5-HT was increased significantly in suspensions of platelets activated with thrombin (PRP+thrombin, 28 +/- 1.7 microM) or collagen (PRP+collagen, 27 +/- 2.5 microM) compared with suspensions of unactivated platelets (PRP+saline, 2.3 +/- 0.8 microM) and PPP. During myocardial ischaemia and reperfusion, tirofiban, a specific inhibitor of platelet glycoprotein (GP) IIb-IIIa receptors (100 microg kg(-1), I.V., followed by 5 microg kg(-1) min(-1)), significantly reduced the increase in the concentration of 5-HT in cardiac venous plasma from ischaemic region. Nerve activity of single-unit cardiac afferents was recorded from the left sympathetic chain (T2-T5) in anaesthetized cats. Eighty ischaemically sensitive and seven ischaemically insensitive cardiac afferents were identified. Tirofiban reduced the ischaemia-related increase in activity of seven cardiac sympathetic afferents by 50 %. Injection of 1.5 ml of PRP+collagen or PRP+thrombin into the left atrium (LA) increased activity of 16 cardiac afferents. Tropisetron (300 microg kg(-1), I.V.), a selective 5-HT(3) receptor antagonist, eliminated the afferent's responses to platelets activated with collagen or thrombin. Moreover, LA injection of 5-HT (20-40 microg kg(-1)) and PBG (100 microg kg(-1)), a 5-HT(3) receptor agonist, stimulated nine ischaemically sensitive cardiac sympathetic afferents, significantly increasing the activity of these afferents. However, injection of alpha-M-5-HT (100 microg kg(-1), LA), a 5-HT(2) receptor agonist, stimulated only two of the nine ischaemically sensitive cardiac afferents, and thus did not significantly alter impulse activity of this group of afferents. Both the 5-HT(1) (5-CT, 100 microg kg(-1), LA) and 5-HT(4) receptor agonists (SC53116, 100 microg kg(-1), LA) did not stimulate any of the nine afferents tested. Tropisetron (300 microg kg(-1), I.V.) also eliminated the response of seven ischaemically sensitive cardiac afferents to exogenous 5-HT and attenuated the ischaemia-related increase in activity of nine cardiac sympathetic afferents by 41 %. Conversely, LA injection of 5-HT (40 microg kg(-1)) did not stimulate any of seven ischaemically insensitive cardiac afferents, although this group of afferents consistently responded to bradykinin (3 microg, LA). These data indicate that during myocardial ischaemia the activated platelets stimulate cardiac sympathetic afferents, at least in part, through a 5-HT(3) receptor mechanism.
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PMID:Activated platelets contribute to stimulation of cardiac afferents during ischaemia in cats: role of 5-HT(3) receptors. 1241 32

Renin is commonly known as a secretory glycoprotein, which is expressed, stored and released in a regulated manner by the kidney. Besides this, a number of extrarenal tissues, such as adrenal gland and heart express or internalise renin. In the heart a local RAS may exert prohypertrophic, proliferative, antiproliferative or apoptotic properties. The local RAS in kidney, adrenal gland and heart are each unique and their modes of action are distinct. This is due to the expression of different renin transcripts and different intracellular sorting and transport events for renin. In the rat kidney exclusively the commonly known preprorenin is expressed encoding for secretory renin. This is targeted to lysosomes, which become secretory renin granules. The cells of the rat adrenal cortex express preprorenin as well, but this is partially targeted to the regulated secretory pathway. Rat adrenocortical cells additionally express an alternative renin transcript, termed exon1A renin, which encodes for a truncated prorenin that is imported into mitochondria. Its function is not known to date. Interestingly, in the rat heart exclusively the alternative transcript is expressed. Even in hypertrophic hearts or after myocardial infarction, preprorenin remains undetectable. Exon1A renin transcript levels, in contrast, markedly increased after myocardial ischemia. This provides a new molecular basis for a function of locally expressed renin. In addition, there are different pathways of renin internalisation by cardiac cells. A mannose-6-phosphate receptor mediated uptake has been described. We recently described another pathway independently of the mannose-6-phosphate receptor. Such a pathway is apparently of functional significance. Subsequent generation of angiotensins and myocyte hypertrophy and proliferation by prorenin through angiotensin generation has been described.
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PMID:Intracellular sorting of renin: cell type specific differences and their consequences. 1250 54

Recent clinical trial evidence supports an inflammatory etiology in acute ischemic heart disease. When a segment of coronary artery becomes inflamed, important cytokines, such as tissue factor, are released, facilitating thrombosis. Serum inflammatory markers are elevated in most acute coronary syndrome patients at presentation. Mortality risk has been shown to be associated with increased levels of high-sensitivity C-reactive protein (CRP), interleukin 6, and serum vascular cell adhesion molecule. Platelets, which are rich in inflammatory mediators (CD40 and its ligand thrombospondin, and phospholipase A2), also supply important triggers for the inflammatory cascade. In addition, more than 35 platelet-associated messenger ribonucleic acid mediators involved in arterial injury and inflammation have been found. The use of biomarkers of inflammation, such as CRP, and of the sequelae of embolization, such as troponin, provide a window into the underlying pathophysiology of acute ischemic heart disease. New agents from three distinct drug classes have recently flooded the therapeutic armamentarium. Decision-making is further complicated by the choice of an invasive (aggressive) or a medical (conservative) strategy of management with respect to coronary revascularization. For patients at highest risk, aspirin, beta-blockers, nitrates, and a statin should be given, and clopidogrel, enoxaparin, a glycoprotein (GP) IIb/IIIa inhibitor, plus an invasive strategy should be considered. For intermediate- and low-risk patients, a "sliding-scale" approach may be best. Decisions about the three classes of antithrombotics--low-molecular-weight heparins, GP IIb/IIIa inhibitors, and thienopyridines--along with whether to adopt an early invasive strategy, should be made on an individual basis.
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PMID:A guide to therapeutic decision-making in patients with non-ST-segment elevation acute coronary syndromes. 1264 50

Depression represents an independent risk factor for developing ischemic heart disease, with platelet hyperactivity possibly serving as an important mediator of this association. In this pilot study we analyzed platelet surface activation markers in response to two stimuli, mental stress and physical activity. Using flow cytometry, we quantified the presence of two functional activation-dependent glycoprotein receptors on platelets' surface (P-selectin, GP53). Platelet reactivity was assessed as the difference in markers' fluorescence intensity before and after stimulation. We included 10 depressed psychiatric inpatients and 10 age- and sex-matched healthy subjects in our study. There was a significant rise in platelet activation markers in both groups associated with the stress protocol. When the effect of stressors was analyzed separately, strenuous physical activity was found to lead to a significant rise in platelet activation markers in depressed patients but not in healthy subjects, although values indicated a higher baseline level of activation in healthy subjects. These preliminary results lend partial support to the hypothesis of an exaggerated platelet reactivity after physical activity in depression, thus possibly contributing to an increased cardiovascular risk in this disorder.
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PMID:Effect of mental and physical stress on platelet activation markers in depressed patients and healthy subjects: a pilot study. 1526 5

First Russian glycoprotein (GP) IIb-IIIa antagonist, preparation Monafram, is the F(ab')2 fragment of anti-GP IIb-IIIa monoclonal antibody FRaMon. In in vitro experiments it was shown that Monafram blocked platelet aggregation induced by ADP and thrombin; reduced secretion from platelet granules; and due to simultaneous interaction with two GP IIb-IIIa molecules almost irreversibly bound to platelet surface. Monafram clinical trials were performed in healthy volunteers (n = 10) and in patients with ischemic heart disease undergoing high risk coronary angioplasty (n = 153). Monafram intravenous bolus administration at 0.25 mg/kg decreased ADP-induced platelet aggregation by more than 90, 80, 60 and 30% at 1, 12, 24 and 72 h after injection, respectively. No significant differences were detected between antiaggregatory effects of Monafram and ReoPro introduced at 0.25 mg/kg bolus + 12 h infusion at 0.125 microg/kg per min. Durable inhibition of aggregation after Monafram administration was mediated by platelet-bound preparation--free Monafram was cleared from plasma within 12 h, while platelet-bound preparation occupied more than 90, 70-80 and 40-50% of GP IIb-IIIa at 1, 12-24 and 72 h after injection, respectively. Major bleedings and allergic reactions were detected in none of patients, deep thrombocytopenia--in one patient and antibodies against Monafram--in 5% of patients. Within one month after coronary angioplasty Monafram decreased the number of end points (fatal and nonfatal myocardial infarction and angina recurrence) from 11.4 to 3.3%.
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PMID:[Antiplatelet effects of glycoproteins IIb-IIIa antagonist monafram]. 1534 Oct 84


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