Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum and granulocyte elastase-type protease activities were determined simultaneously with their main plasma proteinase inhibitors such as alpha-1-antitrypsin and alpha-2-macroglobulin in healthy control and atherosclerotic (ATS) subjects. The age-related associations of these parameters were also investigated. Serum elastase-type protease activity increased, but not statistically significantly, with aging in both control and ATS subjects. The enhancement of elastase-type protease activity in sera of ATS patients was significantly (p less than .02) greater than control subjects only in the case of the elderly. The granulocytes' elastase activity was significantly greater in granulocytes derived from both middle-aged and elderly ATS patients (p less than .03 and p less than .06) compared to age-matched control subjects. Alpha-1-antitrypsin was not significantly lower, whereas alpha-2-macroglobulin was significantly lower in sera of ATS subjects compared to age-matched control subjects (p less than .01). The conclusion is that increased elastase-type activity and decreased antiproteinase activity should be considered as potential factors in atherosclerotic arterial wall damage. The similarity of the results in the elderly and the ATS subjects suggest that atherosclerosis is an early aging process.
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PMID:Sera and leukocyte elastase-type protease and antiprotease activity in healthy and atherosclerotic subjects of various ages. 138 Sep 68

The study was aimed at verification of previously found, in animals with experimentally induced atherosclerosis, the disturbances of serum proteinases inhibitors: alpha-2-antiplasmin, alpha-1-antitrypsin and alpha-2-macroglobulin. In humans with hypercholesterolemia the decrease of serum activity of alpha-2-antiplasmin was observed. In humans with hypercholesterolemia and increased serum concentration of triacylglycerols no significant changes in activity of alpha-1-antitrypsin and alpha-2-macroglobulin were found--in comparison with control subjects.
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PMID:[Activity of selected proteinase inhibitors in patients with disorders of lipid metabolism]. 138 11

After cardiac surgery performed with extracorporeal circulation (ECC) involving heart valve prostheses (PHVS, n 12) and after a bypass of the coronary arteries by a venous graft (CABG, n 19), the authors investigated the dynamics of changes of haemostasis on the 1st, 3rd, 6th, 10th and 21st day after operation. As anti-thrombotic treatment after PHVS anticoagulants were used, after CABG thrombocyte inhibitors. On the 1st day after operation in both groups thrombocytes decline, while after the 10th day their numbers increase. From the 6th day there is in both groups a rise of fibrinogen and other proteins of the acute phase (alpha-1-antitrypsin, orosomucoid and ceruloplasmin, while there was a drop of transferrin. On the 3rd and 6th day after operation fibrinolysis activators decline (euglobulin fibrinolysis). These findings suggest an increased risk of thrombophilia during the postoperative period and are probably associated with the release of interleukin-1 after Ecc and the stress of cardiac surgery. In patients with CABG on the 1st day a major drop of thrombocytes occurs, on the 6th day an elevated fibrinogen value was recorded and on the 10th day a reduced fibrinolytic activity, as compared with patients with PHVS. These changes will be, however, associated rather with a greater development of general atherosclerosis in patients with CABG, which leads to a further alteration of haemostasis, rather than with the applied antithrombotic treatment.
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PMID:Changes in haemostasis and proteins of the acute phase following cardiac surgery. 170 76

We studied the antigenic markers of macrophages (Mphs) in atherosclerotic human arteries by immunohistochemistry and compared them with the patterns in Mph subpopulations of tonsil and lymph node, which are also described. The staining of atheroma intimal Mphs was assessed semiquantitatively in the subendothelial, mid, and outer intima. Three patterns of reactivity with Mph antibodies were recognized. (a) Pan-Mph (antibodies HAM56, EBM11, and CD14 group). Staining was maximal in the mid-intimal zone. (b) Subendothelial Mphs (anti-muramidase, anti-alpha-1-antitrypsin and MAC387). In lymphoid tissue, sinusoidal Mphs and a few inflammatory Mphs were stained, as well as blood monocytes. This group of antibodies recognizes Mphs that are likely to be recently blood-derived (RBD-Mphs). (c) Antibodies reactive with various histiocyte populations in lymphoid tissues (anti-Factor XIII; anti-HLA Class II and LN2) also gave maximal staining in the mid-intimal zone, but differences between lesion types suggest that they are recognizing heterogeneous subpopulations of Mphs. These observations demonstrate the heterogeneity of tissue Mphs and suggest that an insight into the dynamics of tissue Mphs can be obtained from the cell phenotype. They indicate that all stages of atherosclerosis can have an outward traffic of Mphs from the blood through the arterial intima.
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PMID:The immunohistochemical heterogeneity of atheroma macrophages: comparison with lymphoid tissues suggests that recently blood-derived macrophages can be distinguished from longer-resident cells. 750 8

In some pathological states such as therosclerosis tissue destruction may be accelerated due to uncontrolled protease release of polymorphonuclear leukocytes and other events such as decreased concentration and/or the inactivation of main protease inhibitor molecules in the serum. In this study, the authors measured the elastase release of polymorphonuclear leukocytes which increased in atherosclerosis independently of the patients aged compared to healthy young subjects. These findings were similar to the response of polymorphonuclear leukocytes separated from healthy elderly subjects. Simultaneously, the main plasma proteinase inhibitors such as alpha-1-antitrypsin and alpha-2-macroglobulin in healthy and atherosclerotic subjects were determined. alpha-1-antitrypsin did not decrease significantly, whereas alpha-2-macroglobulin did in sera of atherosclerotic patients compared to age matched subjects (p < 0.05). In contrast, the activity of porcine pancreatic elastase was more effectively neutralized by the plasma obtained from healthy subjects suggesting diminished antiprotease activity of sera obtained from patients. The authors concluded that increased elastase release and decreased antiproteinase activity should be considered in atherosclerotic arterial wall damage. The similarity of the results in aged and therosclerotic subjects suggests that arteriosclerosis is an earlier aging process.
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PMID:[Serum elastin peptide concentration and human leukocyte elastase/antiproteinase balance in peripheral obstructive atherosclerosis]. 872 58

Chlamydia pneumoniae has been detected in atherosclerotic plaques by various means. Chlamydiae are able to cause persistent infections. Serologically elevated antibody titers are found in severe chronic obstructive pulmonary disease. In atherosclerosis and pulmonary emphysema, inflammatory reactions can be seen by means of light microscopy. Specimens from patients with obliterative arteriosclerosis undergoing thrombendarteriectomy and with advanced emphysema undergoing lung volume reduction surgery were examined using scanning (SEM) and transmission (TEM) electron microscopy, and using immunofluorescence with monoclonal antibodies and antiserum against chlamydiae. SEM shows spherical bodies (SBs) with a diameter from 0.3 microm to 0.6 microm on the surface of the alveoli and bronchioles, as well as in atherosclerotic plaques. In atherosclerosis and emphysema, SBs reveal a double membrane, adherence to collagen fibers, tissue destruction, as well as intracellular and interstitial localization in TEM. They show in parts a densely packed central structure. SBs are seen both in alpha-1-antitrypsin deficiency emphysema and smoker's emphysema. Using immunofluorescence microscopy, spots are seen in corresponding distributions to the SBs. Morphological findings are typical for aberrant chlamydiae seen in persistent infections. Chronic infection and bacterial colonization associated with progressive disease seems to be relevant not only in atherosclerosis but also in pulmonary emphysema.
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PMID:The role of chlamydia in the pathogenesis of pulmonary emphysema. Electron microscopy and immunofluorescence reveal corresponding findings as in atherosclerosis. 1099 81

Production of alpha-1-antitrypsin by human monocytes is an important factor in controlling tissue damage by proteases in the microenvironment of inflammation. Increases of four- to eightfold in levels of native and fragmented forms of alpha-1-antitrypsin have been detected in inflammatory loci in vivo. In this study we have extended our previous observation that the carboxyl-terminal peptide (C-36) of alpha-1-antitrypsin produced by specific proteinase cleavage, when added in its fibrillar form at concentrations of 5 microM or more to monocytes in culture, induces cytotoxic effects. Experiments with synthetic amyloid-forming peptides suggest fibril cytotoxicity to be mediated via a common oxidative stress mechanism. We undertook to determine whether C-36 fibril cytotoxicity also involves this common pathway. Monocytes stimulated with C-36 fibrils for 1 h showed significant elevation in monocyte chemoattractant protein-1 expression, induced reduced nicotinamide-adenine dinucleotide phosphate oxidase activity, increased intracellular lipid peroxidation, altered mitochondrial membrane potential, and increased cytosolic cytochrome c and caspase-3 activity. Treatment of monocytes with C-36 fibrils after 24 h also resulted in increased cytosolic cathepsin D activity, suggesting that lysosomes may also be destabilized over longer periods of time. In contrast, native alpha-1-antitrypsin only showed concentration and time-dependent effects on chemoattractant protein-1 expression, and these appear to be independent of oxidative stress. These results indicate that the cytotoxicity of the fibrillar fragment is mediated via oxidative mechanisms and support important multiple roles for native and also for cleaved forms of alpha-1-antitrypsin in monocyte recruitment and activation during inflammatory processes such as atherosclerosis.
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PMID:Fibrillogenic C-terminal fragment of alpha-1-antitrypsin activates human monocytes via oxidative mechanisms. 1151 75

High-density lipoprotein (HDL) is the most abundant lipoprotein particle in the plasma and a negative risk factor of atherosclerosis. By using a proteomic approach it is possible to obtain detailed information about its protein content and protein modifications that may give new information about the physiological roles of HDL. In this study the two subfractions; HDL(2) and HDL(3), were isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix-assisted laser desorption/ionisation time of flight mass spectrometry. Identified proteins in HDL were: the dominating apo A-I as six isoforms, four of them with a glycosylation pattern and one of them with retained propeptide, apolipoprotein (apo) A-II, apo A-IV, apo C-I, apo C-II, apo C-III (two isoforms), apo E (five isoforms), the recently discovered apo M (two isoforms), serum amyloid A (two isoforms) and serum amyloid A-IV (six isoforms). Furthermore, alpha-1-antitrypsin was identified in HDL for the first time. Additionally, salivary alpha-amylase was identified as two isoforms in HDL(2), and apo L and a glycosylated apo A-II were identified in HDL(3). Besides confirming the presence of different apolipoproteins, this study indicates new patterns of glycosylated apo A-I and apo A-II. Furthermore, the study reveals new proteins in HDL; alpha-1-antitrypsin and salivary alpha-amylase. Further investigations about these proteins may give new insight into the functional role of HDL in coronary artery diseases.
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PMID:Lipoproteomics II: mapping of proteins in high-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry. 1576 60

Human neutrophil elastase (HNE) is present within atherosclerotic plaques where it contributes to matrix degradation and weakening of the vessel wall associated with the complications of aneurysm formation and plaque rupture. It is joined by other extracellular proteases in these actions but the broad range of substrates and potency of HNE coupled with the potential for rapid increases in HNE activity associated with neutrophil degranulation in acute coronary syndromes single this disruptive protease out as therapeutic target in atherosclerotic disease. This review summarises the role of HNE in neutrophil-mediated endothelial injury and the evidence for HNE as a mediator of atherosclerotic plaque development. The therapeutic potential of HNE neutralising antiproteases, alpha-1-antitrypsin and elafin, in atherosclerosis, is discussed.
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PMID:Human neutrophil elastase: mediator and therapeutic target in atherosclerosis. 1828 16

Investigation of the mechanisms of atherosclerosis has determined that inflammation plays a central role in the development, progression, and outcome of acute coronary syndrome (ACS). C-reactive protein (CRP) plasma levels increase in patients with ACS. CPR is an important prognostic marker in ACS, following angioplasty, and in the long-term management of post-infarction patients. Although CRP will remain over time a useful marker, the role and implications of increased plasma concentrations of other acute phase proteins (APPs), such as alpha-1-antitrypsin (A1AT), alpha-1 glycoprotein (A1GP), haptoglobin (HG), ceruloplasmin (CP), and C3c and C4 complement fraction, in patients with ACS are still not completely defined. This short review summarizes the experimental and clinical evidence regarding the role, and the biological and clinical significance of these other APPs in ACS.
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PMID:Acute phase proteins in atherosclerosis (acute coronary syndrome). 1885 39


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