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)

Cholesterol binds to streptolysin O and related bacterial toxins. In normal serum, only a fraction of the cholesterol attached to lipoprotein is available for binding, probably as a cholesterol-peptide complex formed during catabolic breakdown of the lipoprotein. Cholesterol esterase produced by certain organisms--e.g., Staphylococcus pyogenes and Pseudomonas oeruginosa--augments this fraction both in vitro and in vivo. Endogenous esterase similarly increases the amount of cholesterol-peptide complex, a mechanism which may be activated as a feedback process following binding of toxin to the cholesterol component of the complex. These complexes will thus supply a readily available means of binding bacterial toxins before antibody formation begins; Cholesterol-peptide complexes, either alone or modified by binding to toxin, may function as autoantigens. It is postulated that immune complexes so formed may be involved in atherosclerosis either by directly damaging vessels walls or by cross-reaction of antibody with cell-membrane-bound lipoproteins which equilibrate with plasma-lipoproteins.
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PMID:Functional role of cholesterol in infection and autoimmunity. 4 49

Over a period of 11 years, commencing in December 1967, 31 cardiac transplants, 10 orthotopic and 21 heterotopic, were performed at Groote Schuur Hospital. Two patients with orthotopic transplants have a long survival, 1 for 7 1/2 and 1 for 9 1/2 years, and 1 with a heterotopic transplant for 4 years. Eighteen patients have died, and autopsy was performed from 13 to 623 days postoperatively. Rejection of the donor heart was found in 61,1% and was the cause of death in 44,4% of cases. Infection, attributable to immunosuppression, was a common finding and consisted of extensive pneumonia, usually due to Klebsiella aerogenes and Pseudomonas aeruginosa (38,8%), herpesvirus infection (38,8%), cytomegalic virus infection (37,5%), aspergillosis and other opportunistic infections. A combination of cardiac rejection and infection accounted for most of the deaths. The cardinal microscopic features of acute rejection were interstitial lymphocytic infiltration and myocytolysis, while chronic rejection was typified by obliterative myo-intimal proliferation of coronary arteries, with concurrent lipid deposition in the major coronary arteries. These lesions resembled atherosclerosis and caused graft failure due to myocardial ischaemia. Ultrastructurally, severe myofibre damage was reflected in extensive loss of cytoplasmic myofilaments. The advantages of heterotopic over orthotopic transplantation are discussed.
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PMID:The pathology of human cardiac transplantation: an assessment after 11 years' experience at Groote Schuur Hospital. 39 Jul 37

We report a retrospective, clinicopathologic study of 139 patients who died during treatment of a severe burn. Fifty-three percent of the patients had central nervous system (CNS) complications-infections, cerebral infarcts and hemorrhages, metabolic encephalopathies, central pontine myelinolysis, and cerebral trauma. Children and adults were equally affected. Sixteen percent of the patients had a CNS infection. Candida species, Staphylococcus aureus and Pseudomonas aeruginosa caused almost 80% of them. S. aureus and candida caused cerebral microabscesses and septic infarcts. P. aeruginosa caused meningitis and infarcts due to meningitis. CNS infections arose as a result of spread from a systemic source. The major risk factors for CNS infection were an extensive burn, S. aureus endocarditis, and a burn wound infection due to candida or P. aeruginosa. Patients with burns of less than 30% of the surface area of their body, those without a systemic infection, and those in the first week after their burn were at low risk. Eighteen percent of the patients had cerebral infarcts. In almost half the patients, the infarcts were caused by septic arterial occlusions or other complications of the burn, viz, disseminated intravascular coagulation (DIC) and septic shock. In only one-third of the patients were infarcts due to atherosclerosis, atrial fibrillation, or other causes prevalent in the general population. Intracranial hemorrhages were only one-fifth as frequent as infarcts and were due to DIC and thrombocytopenia, caused by bacteremia. Diagnosis during life was difficult, because the neurologic picture of focal cerebral lesions and meningitis was indistinguishable from that of metabolic encephalopathies, and because many patients had more than 1 neurologic complication. However, our results suggest that a clinical approach that includes analysis of risk factors for CNS infection, cerebral imaging, examination of cerebrospinal fluid, and tests for DIC can lead to a neurologic and microbiologic diagnosis in most patients.
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PMID:Central nervous system complications of thermal burns. A postmortem study of 139 patients. 152 3

The multiligand receptor, low density lipoprotein receptor-related protein (LRP), is implicated in processes such as atherosclerosis and fibrinolysis through its mediation of the catabolism of lipoproteins, proteases, and protease inhibitor complexes. The hepatoma cell line Hep G2 expresses LRP and has been used widely to investigate the catabolism of LRP ligands including tissue-type plasminogen activator (tPA). However, the mechanism and degree by which tPA interacts with Hep G2 has been reported with some inconsistencies which may reflect variation in their level of LRP expression. To address this possibility we characterized, antigenically and functionally, LRP expression in high and low passage Hep G2 cells both from the parental line (ATCC sourced) and a cloned subline, a16. The LRP contribution to 125I-tPA binding varied from 65% for high passage a16 cells, to 20% for low passage parent cells as quantified by inhibition in the presence of 39-kD receptor associated protein (RAP) which prevents binding of all known LRP ligands. The same trend in LRP expression among Hep G2 sublines was further evident in their ability to degrade 125I-tPA and survive Pseudomonas exotoxin A challenge. These results imply wide variability in basal LRP expression among Hep G2 lines dependent on cell lineage and long-term culture conditions.
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PMID:Low density lipoprotein receptor-related protein (LRP) expression varies among Hep G2 cell lines. 961 Sep 60

This paper aimed to examine the literature for cases of coronary artery stent infection in order to provide comprehensive data to clinicians regarding its prevalence, clinical presentations, and possible treatments. Coronary artery stenting was initially reported in 1987. Stenting of the coronary arteries is now used in 40-60% of all interventional coronary artery procedures. The understanding of the pathophysiology of coronary artery disease is evolving. It has been suggested that atherosclerosis may be a complication of an infectious etiology. By using a stent to treat coronary artery disease, a foreign body is directly juxtaposed with an area of inflammation. The first reported case of an infected coronary artery stent was in 1993. Although this is an exceedingly rare event, the associated mortality is alarmingly high. Analysis of the literature reveals a total of four reported cases of coronary artery stent infection. Symptoms of stent infection present days to weeks after the initial coronary intervention. All four patients developed fevers and at least two patients developed postintervention angina. In patients who have had a coronary artery stented, the presence of angina and fevers should make the clinician suspicious for a stent-related infection. Two of the patients had infection with Pseudomonas aeruginosa, which seems to be an unusual organism for a catheter-related infection. Surgical removal of the infected stent and artery complex was performed on nearly all cases. Despite aggressive measures, the majority of patients died. Few data are available on the long-term risk for coronary artery stent infection. In a patient who has undergone coronary artery stent placement, the clinician must be very sensitive to fever, return of angina, and bacteremia. The complication rate at the present time does not warrant the use of prophylactic antibiotics prior to high-risk procedures (e.g., dental procedures). Furthermore, the low infection rate of coronary artery stents may be a result of the inflammatory nature of atherosclerosis, which may provide a protective benefit against bacterial infection of the stent.
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PMID:Coronary artery stent infection. 1109 26

Toll-like receptor 4 (TLR4)-mediated recognition of lipopolysaccharide (LPS) is required for efficient recognition of Gram-negative bacterial infections. Two commonly occurring mutations in the human TLR4 gene (Asp299Gly and Thr399Ile) have recently been shown to be associated with blunted physiological responses to inhaled LPS, and with increased risk of Gram-negative bacteraemia in sepsis patients and reduced risk of atherosclerosis in an Italian population. Here we show that monocytes from individuals heterozygous for both mutations in the TLR4 gene exhibit no deficit in recognition of LPS of Escherichia coli, Neisseria meningitidis, Bacteroides fragilis, Yersinia pestis, Chlamydia trachomatis, Porphyromonas gingivalis, or Pseudomonas aeruginosa. We propose that the relatively high frequency of these mutations in the Caucasian population may reflect modified responses of carriers to alternative TLR4 agonists.
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PMID:Monocytes heterozygous for the Asp299Gly and Thr399Ile mutations in the Toll-like receptor 4 gene show no deficit in lipopolysaccharide signalling. 1279 70

In order to investigate the possible relationship between atherosclerosis and chronic Pseudomonas aeruginosa infection, 66 Wistar rats were given five separate intratracheal inoculations of either P. aeruginosa or sterile saline at 4-week intervals. The rats were divided into four groups: group 1 was infected with P. aeruginosa and fed a diet containing cholesterol 1% w/v; group 2 was infected with P. aeruginosa and fed a normal diet; group 3 was not infected and was fed a diet containing cholesterol 1% w/v; and group 4 (the control group) was not infected and was fed a normal diet. One month after the final inoculation, the rats were killed humanely; computerised image analysis was used to evaluate sections of the aorta and heart, and the maximal wall thickness of the aorta and coronary artery. The aortic wall thickness was significantly greater for group 1 (329.53 +/- 58.06 microm) compared to groups 2 (190.59 +/- 27.81 microm; p < 0.0001), 3 (262.90 +/- 61.12 microm; p < 0.0004) and 4 (158.00 +/- 30.30 microm; p < 0.0001). Similarly, the coronary artery wall thickness was significantly greater for group 1 (72.96 +/- 10.67 microm) compared to groups 2 (35.07 +/- 8.53 microm; p < 0.0001), 3 (41.45 +/- 10.22 microm; p < 0.0001) and 4 (32.30 +/- 5.27 microm; p < 0.0001). These findings strengthen the hypothesis that chronic infection plays a role in the pathogenesis of atherosclerosis.
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PMID:Effect of chronic Pseudomonas aeruginosa infection on the development of atherosclerosis in a rat model. 2601 Nov 49

Enolase, is a glycolytic enzyme ubiquitous in higher organisms, where it forms tissue specific dimers of isoforms, also found in the cytoplasm of fermentative bacteria. The aim of this work was to identify enolase-like proteins in the cell wall of some Gram-negative bacteria using antibodies against human beta-enolase, an isoenzyme specific to skeletal and heart muscles. Cell wall outer membrane protein (OMP) preparations were obtained from 9 strains of Enterobacteriaceae and one of Pseudomonas aeruginosa. Specific enzymatic enolase activity was detected in the supernatant fractions of cytosolic and inner membrane material, but not in purified OMP preparations. Rabbit polyclonal antibodies specific against human beta-enolase were prepared and purified using immobilized human beta-enolase in affinity chromatography. In SDS-polyacrylamide gel electrophoresis and immunoblotting assay of purified OMP preparations, rabbit anti-enolase antibody interacted specifically with a few OMPs, of which a 45-kDa band also interacted with human sera of patients presenting Buerger disease and atherosclerosis. The most distinct interaction of human sera was observed with a 45-kDa OMP of Klebsiella pneumoniae. This protein was further isolated from K. pneumoniae cell mass in two ways, namely preparative SDS-polyacrylamide gel electrophoresis and specific affinity chromatography using immobilized affinity-purified rabbit antibody raised against human beta-enolase. The data obtained from tandem mass spectrometry tryptic peptide analysis and sequence comparison of human and bacterial enolases using protein databases, could reveal the similarity in the epitopes between membrane enolase-like protein from Klebsiella and human beta-enolase. The results show that the protein present in all studied strains has a common epitope on human beta-enolase. These data raise the question whether such a bacterial protein might be a marker for detecting and monitoring damage to skeletal and heart muscles.
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PMID:Antibodies against human muscle enolase recognize a 45-kDa bacterial cell wall outer membrane enolase-like protein. 1598 23

It has been demonstrated that both hypercholesterolemia and infectious agents are contributing factors in atherosclerosis but their combined effect on the pulmonary vascular bed is not known. To answer this question, the authors tried to demonstrate the effects of recurrent infection on pulmonary parenchyma and vascular system in cholesterol-fed rats. Sixty-six rats were randomly divided into 4 groups: Groups I (control), II (cholesterol-rich diet), III (recurrent pulmonary Pseudomonas aeruginosa infection), IV (cholesterol-rich diet + recurrent infection). After 6 months serum cholesterol levels didn't increase in any of the groups. Central pulmonary artery wall thickness was increased in group IV (P < .0001). Although not significant, peripheral pulmonary artery wall thickness was increased in group IV. In rats fed on a cholesterol-rich diet, recurrent infection caused a significant increase in atherosclerosis, although serum cholesterol levels didn't increase. Infection and cholesterol-rich diet have a synergistic effect on atherosclerosis in the pulmonary vascular system in rats even in the absence of hypercholesterolemia.
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PMID:The effects of recurrent Pseudomonas aeruginosa infection on pulmonary parenchyma and vasculature in rats fed on a cholesterol-rich diet. 1706 Jan 72

The human enzyme paraoxonase-2 (PON2) has two functions, an enzymatic lactonase activity and the reduction of intracellular oxidative stress. As a lactonase, it dominantly hydrolyzes bacterial signaling molecule 3OC12 and may contribute to the defense against pathogenic Pseudomonas aeruginosa. By its anti-oxidative effect, PON2 reduces cellular oxidative damage and influences redox signaling, which promotes cell survival. This may be appreciated but also deleterious given that high PON2 levels reduce atherosclerosis but may stabilize tumor cells. Here we addressed the unknown mechanisms and linkage of PON2 enzymatic and anti-oxidative function. We demonstrate that PON2 indirectly but specifically reduced superoxide release from the inner mitochondrial membrane, irrespective whether resulting from complex I or complex III of the electron transport chain. PON2 left O(2)(-) dismutase activities and cytochrome c expression unaltered, and it did not oxidize O(2)(-) but rather prevented its formation, which implies that PON2 acts by modulating quinones. To analyze linkage to hydrolytic activity, we introduced several point mutations and show that residues His(114) and His(133) are essential for PON2 activity. Further, we mapped its glycosylation sites and provide evidence that glycosylation, but not a native polymorphism Ser/Cys(311), was critical to its activity. Importantly, none of these mutations altered the anti-oxidative/anti-apoptotic function of PON2, demonstrating unrelated activities of the same protein. Collectively, our study provides detailed mechanistic insight into the functions of PON2, which is important for its role in innate immunity, atherosclerosis, and cancer.
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PMID:One enzyme, two functions: PON2 prevents mitochondrial superoxide formation and apoptosis independent from its lactonase activity. 2053 Apr 81


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