Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.2.1.1 (ACS)
78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute coronary syndrome encompasses the entities acute MI, unstable AP and sudden cardiac death. The syndrome of unstable AP covers a very heterogenous group of patients. Recent pathological post-mortem investigations have revealed, that unstable AP leading to MI or sudden cardiac death is frequently preceded by microinfarctions. Despite the fact that thrombus formation is recognized as the major cause, the role of coronary artery spasm seems also important. Therefore, the pathological hallmark of ACS is at present thought to be caused by an active coronary plaque (the culprit lesion), which is often the site of intermittent occlusion and of thrombus formation, with or without vasospasm. The release of myocardial cell constituents in connection with these microinfarctions is to be expected. In order to detect these, diagnostic tools sensitive to myocardial injury and specific for myocardial tissue must be employed. According to WHO the criteria for the diagnosis of acute MI are based on clinical history, electrocardiographic changes, and enzymes in serum. Although these criteria are quite adequate in most cases, they are not present or easily discernible in all acute MI patients. The clinical symptoms are and will remain insensitive and nonspecific indicators of acute MI. Electrocardiographic alterations are carefully described, but sometimes less applicable due to non-interpretable ECG's. During the last decades, activity measurements of cardiac enzymes, and especially the isoenzymes of CK and LD, have become the final arbiters by which myocardial damage is diagnosed or excluded. However, they are not fully cardiospecific and have a low sensitivity to detect MMI, retaining a high specificity. Improved immunoassays have therefore been developed measuring the mass concentration of CK-MB instead of its catalytic activity, as well as immunoassays measuring structural proteins of the heart i.e., TnT, a tropomyosin-binding protein of the troponin regulatory complex located on the thin filament of the contractile apparatus of the myocyte; and MLC, a component of the thick filament of the contractile apparatus of the myocyte. We, and others, have shown that minor ischaemic myocardial injury can be detected by CK-MB mass immunoassays in around one-fourth to one-third of patients with unstable AP or in whom an acute MI has been ruled out. However, the prognostic significance of this identification has not been investigated. A priori, it is known that 5-20% of patients with unstable AP have a poor prognosis, with progression to acute MI or cardiac death within the first year. Additional, non-Q wave MI may also be considered a relatively unstable condition associated with a lower initial mortality but a higher risk of later MI/cardiac death. It is of further importance, that although the incidence of unrecognized MI is less than that of clinically apparent MI, the long-term prognosis for unrecognized MI appears to be similar to, and as serious as, that following detected MI. Therefore, in order to follow-up this subgroup identification based on CK-MB mass levels, we subsequently carried out a prognostic study. It demonstrated a significantly increased risk of cardiac events (i.e., non-fatal acute MI, cardiac death) in patients with significant fluctuations of CK-MB mass in serum. A similar observation has been supported by others using the rate of change in serial samples of CK-MB mass. Further, we demonstrated a good correlation between elevated CK-MB mass levels and a poor prognosis, when using a fixed discrimination limit. However, an increasing number of CK-MB mass immunoassays have been developed, and a standardization of CK-MB mass is urgently needed, as at present each laboratory determines its own reference levels and discriminatory values leading to the risk of diagnostic confusion. (ABSTRACT TRUNCATED)
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PMID:Creatine kinase isoenzyme MB mass, cardiac troponin T, and myosin light chain isotype 1 as serological markers of myocardial injury and their prognostic importance in acute coronary syndrome. 950 65

The CD40-CD40L interaction, which was initially shown to have important roles in the T cell-mediated activation of B cells during humoral immune responses, is now known to have roles in activation of endothelial cells, smooth muscle cells, and macrophages within atherosclerotic plaques. Recently, CD40L expression was found in activated platelets in the thrombus in vivo and CD40L was reported to be responsible for the platelet-mediated activation of endothelial cells in vitro. To investigate the activation status of platelets in coronary artery disease patients, we tested expression levels of CD40L, and platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31) in platelets isolated from peripheral blood, using flow cytometric analysis. Twenty-nine patients with acute coronary syndrome (10 acute myocardial infarction and 19 unstable angina patients) were compared with 14 normal subjects or 14 stable angina patients. In platelets isolated from normal subjects, the expression of CD40L was not detected in all subjects. In the patients with acute coronary syndrome, the average level of CD40L showed a significant increase (p = 0.0028), while stable angina patients did not have any increase when compared to normal subjects. Patients with more complex lesions or vessel occlusion tended to have a high platelet CD40L level compared to patients who do not. The expression levels of CD31 were increased in a small portion of the ACS patients. These data indicate that the rupture of plaque and subsequent formation of thrombus may lead to the activation of CD40L expression in circulating platelets of ACS patients.
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PMID:CD40L activation in circulating platelets in patients with acute coronary syndrome. 1064 Jul 91

Recent studies provide evidence that infectious agents play a causal role in the pathogenesis of atherosclerosis. In this respect, a chronic persistent Chlamydia pneumoniae infection, indicated by the presence of chlamydial heat shock protein 60 (cHSP 60), is of central interest. Both cHSP60 and endogenous human (h) HSP60 are upregulated under stress conditions in intimal cells and serve as a target for cross-reactive cytotoxic HSP-serum-antibodies. Therefore, the present study evaluates the expressions of both HSP60 homologues in advanced human coronary lesions and a correlation between intimal tissuebound protein and serum antibodies (Ab) to HSP65. Coronary atherectomy specimens retrieved from 114 primary target lesions of patients with acute coronary syndrome (ACS; n=46) or stable angina (SA; n=68) were assessed immunohistochemically for the presence of cHSP60 and hHSP60. Chronic persistency of Chlamydia pneumoniae was additionally examined by transmission electron microscopy. Blood samples from30 patients were tested for anti-Chlamydia pneumoniae-IgG/IgA- and anti-HSP65-Ab titers and for serum CRP levels. Coronary plaques revealed immunoreactive cHSP60 in 47% and hHSP60 in 57% of the lesions colocalized within macrophages/foam cells. Chlamydia in foam cells most often presented ultrastructural patterns that pointed to the persistency of the pathogen. Intact, non-atherosclerotic vessels showed no signals. Mean expressions were 3.1% for cHSP60 and 3.3% for hHSP60. As a central finding, the expression of both HSP homologues was significantly (each p<0.001) higher in ACS lesions compared to SA lesions (cHSP60: 6.2 vs 1.0%, and hHSP60: 7.2 vs 0.7%). Moreover, we found positive correlations between both determinants in ACS and SA lesions (r=0.41, r=0.37; p<0.01). Most interestingly, cHSP60 revealed no relationship with anti-Chlamydia pneumoniae-IgG/IgA titers, whereas expression of cHSP60 as well as that of hHSP60 correlated with anti-HSP65-Ab titers (r=0.50, p<0.01, and r=0.42, p<0.05, respectively).cHSP60 and hHSP60 colocalize within coronary primary atheroma, most prevalent in lesions associated with ACS. For the first time, our data demonstrate a significant correlation between the intimal expression of these HSP60 homologues and serum HSP65 antibodies, thereby suggesting that humoral immune reactions to bacterial and human HSPs may play an important role in coronary atherosclerosis and plaque instability.
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PMID:[Chlamydial and human heat shock protein 60 homologues in acute coronary syndromes. (Auto-)immune reactions as a link between infection and atherosclerosis]. 1281 94

BACKGROUND: Atherosclerosis lesions contain abundant immunoglobulins complexed with oxidized LDL (OxLDL) that are endocytosed by macrophages to form foam cells. While recent evidence supports a role for the macrophage scavenger receptor pathway in 75-90% of OxLDL uptake, in vitro evidence suggests another potential uptake pathway could involve autoantibody binding to IgG subclass-specific Fc receptors. OBJECTIVE AND METHODS: To address this mechanism from an in vivo standpoint, the objective of this study was to utilize flow cytometry to prospectively determine monocyte Fcgamma (FcR) I, II, and III receptor expression levels in patients with acute coronary syndrome (ACS, n = 48), diabetes mellitus (DM, n = 59), or neither (C, n = 88). RESULTS: Increased FcR I expression was found in the ACS versus DM groups [geometric mean, (95% CI) = 2.26 (2.07, 2.47) versus 1.83 (1.69, 1.98) (p < 0.001)] and versus C [1.90 (1.78, 2.03) (p = 0.005)]. Similar relationships were found with both the FcR II receptor [ACS mean = 4.57 (4.02, 5.19) versus DM 3.61 (3.22, 4.05) (p = 0.021) and versus C 3.86 (3.51, 4.24) (p = 0.09)] and FcR III receptor [ACS mean = 1.55 (1.44, 1.68) versus DM 1.36 (1.27, 1.46) (p = 0.038) and versus C 1.37 (1.30, 1.45) (p = 0.032)]. There was no difference between DM and C groups in FcR I, II or III expression. CONCLUSIONS: This in vivo data supports a possible second OxLDL-autoantibody macrophage uptake mechanism through an Fc receptor-mediated pathway and a potential relationship between atherosclerotic plaque macrophage FcR levels and ACS.
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PMID:Association between monocyte Fcgamma subclass expression and acute coronary syndrome. 1567 33

Non-ST elevation Acute Coronary Syndrome (NSTE-ACS) is a myocardial ischemic disorder frequently caused by coronary artery plaque rupture and partial or transient vessel occlusion. Platelets and thrombin play pivotal roles in formation and propagation of thrombus at the site of plaque disruption and embolization into the vascular bed. With the outgoing development of antithrombotic, antiplatelet, and mechanical therapies, the management of NSTE-ACS is constantly evolving. Heparins are the cornerstone of antithrombotic therapy in the current management of NSTE-ACS. Unfractionated heparin and fractionated heparins like enoxaparin have been studied in several large clinical trials and found to be effective in reducing death and myocardial infarction rates. For medical management alone or primarily (conservative strategy), enoxaparin has been shown to be superior to unfractionated heparin. With an early invasive strategy providing better clinical outcome compared to a conservative strategy, the paradigm of ACS management has shifted in favor of early (within 48 hours of admission) cardiac catheterization. The effectiveness of enoxaparin compared to unfractionated heparin is now being re-considered in the era of poly-pharmacotherapy and an early invasive strategy for ACS management. We review the role of enoxaparin in the contemporary treatment of NSTE-ACS utilizing recent clinical trial data.
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PMID:Enoxaparin in clinical practice and clinical trials of non-ST-elevation Acute Coronary Syndrome (NSTE-ACS). 1605 1

There is a combination of inflammation inside unstable atherosclerotic plaque and reparation of its fibrous cover. Increase of the inflammation activity with production of various proteases results in thinning of fibrous cover and loss of normal intercellular and matrix-cell interactions. Later rupture of the plaque takes place with development of a variant of ACS.
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PMID:[Morphogenesis of unstable atherosclerotic plaque and its role in development of acute coronary syndrome (ACS)]. 1607 16

NSTE-ACS is a complex clinical event characterized by a variable degree of myocardial ischemia and triggered, in most patients, by a rupture of a vulnerable plaque that leads to acute intraluminal nonocclusive thrombosis. Traditionally, acute management strategies for NSTE-ACS have been aimed at identification of vascular areas with discrete atheroma and revascularization of the affected myocardium. Studies that have evaluated invasive strategies in NSTE-ACS suggest that the rates of hard clinical events are similar for both intensive medical treatment and early invasive management strategies. As shown recently in the Cooperative Cardiovascular Project study, intensive therapy with beta-blockers appears to be a viable management option that has comparable outcomes in most patients with NSTE-ACS. Although several different treatment strategies have been advocated in the management of NSTE-ACS, the available evidence-based information does not fully support some of these traditional approaches. Future prospective, well-controlled trials are needed to fully ascertain the role of invasive and other medical management strategies in patients with NSTE-ACS. Long-term aggressive management of established risk factors for CAD is unquestionably the most prudent and cost-effective therapeutic approach in the long-term management in patients recovering from NSTE-ACS.
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PMID:Treating non-ST-segment elevation ACS. Pros and cons of current strategies. 1620 5

NSTE ACS is a clinically significant problem. Endothelial dysfunction triggered by traditional cardiovascular risk factors (and perhaps by other as yet unidentified risks) in the susceptible host leads to the formation and development of atherosclerotic plaque. Inflammatory mediators and mechanical stresses contribute to plaque rupture by disrupting the protective fibrous cap. In about 25% of patients who have ACS, typically those who are younger, female, or smokers, plaque erosion seems to be the main underlying pathologic mechanism. Endothelial alteration, inflammation,or exposure of the lipid core results in the release of TF, vWF, and PAF. The release of these factors leads to platelet activation and aggregation as well as to the formation of a fibrin clot, resulting in arterial thrombosis that occludes the vessel. A variety of factors, including circulating catecholamines, LDL levels, blood glucose levels, and systemic thrombogenic factors, can affect the extent and stability of the thrombus, thereby determining whether the occlusion is complete and fixed, labile and nonocclusive (NSTE ACS),or clinically silent resulting in a mural thrombus and plaque growth. The acute treatment of NSTEACS is directed at interrupting the prothrombotic environment surrounding the ruptured plaque; thus, antiplatelet agents such as aspirin, clopidogrel, and glycoprotein IIb/IIla receptor antagonists,as well as anticoagulants such as heparin, are the mainstays of early therapy.
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PMID:Pathogenesis and early management of non-ST-segment elevation acute coronary syndromes. 1632 54

Coronary plaque rupture and the following formed thrombus have been revealed the cause of acute coronary syndrome. This evidence had been proposed by the pathologists 100 years ago; however, the intravascular imaging such as intravascular ultrasound (IVUS) or coronary angioscopy has revealed the clinical evidences in live human being. Thrombus and yellow plaque detected by coronary angioscopy as well as the ruptured fibrous cap detected by IVUS are the characteristics for the lesion of ACS, which does not show the significant stenosis. Thus, ACS lesion should be diagnosed by IVUS or coronary angioscopy.
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PMID:[Acute coronary syndrome diagnosed by the intravascular imaging]. 1661 85

Contemporary clinical and laboratory data have challenged our classical concepts of the pathogenesis of the acute coronary syndromes [ACS]. Indeed, several independent lines of clinical evidence have supported that the critical stenoses cause only a fraction of the ACS. Acute myocardial infarction is believed to be caused by rupture of a vulnerable coronary-artery plaque that appears as a single lesion on angiography. However, plaque instability might be caused by pathophysiologic processes, such as inflammation, that exert adverse effects throughout the coronary vasculature and therefore result in multiple unstable lesions. Recent studies have demonstrated that ruptured or vulnerable plaques exist not only at the culprit lesion but also in the whole coronary artery in some ACS patients. It has also been reported that a ruptured plaque at the culprit lesion is associated with elevated C- reactive protein and other inflammatory markers, which indeed indicate a poor prognosis in patients with ACS. Also, multiple plaque rupture is associated with systemic inflammation, and patients with multiple plaque rupture can be expected to show a poor prognosis. Therefore some ACS patients [20-40%] may harbor multiple complex coronary plaques that are associated with adverse clinical outcomes. It should be accepted that this ACS population represent a part of the spectrum of the ACS, and in particular in this group of patients treatment should focus not only on the stabilization of the culprit site but also warrants a broader approach to systemic stabilization of the arteries. However, recurrent cardiovascular events in this population still remain unacceptably high, indicating that plaque rupture or vulnerability of multiple plaques is a current challenge in the management of ACS patients.
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PMID:[From the single vulnerable plaque, to the multiple complex coronary plaques. From their basis, to the modern therapeutic approach. A clinical reality in the spectrum of the acute coronary syndromes]. 1683 Aug 32


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