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)

The changes in the immunological indices characterizing the T and B immunity system and also in biological resistance of atherosclerosis patients were studied under conditons of the use of the antireticular cytotoxic serum microdoses. A possibility of employing the ACS for stimulation of the immune system was demonstrated.
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PMID:[Antireticular cytotoxic serum as an agent for stimulating the immunity system]. 8

Plasmin inhibition by alpha 2-antiplasmin (alpha 2AP) is regulated by the vascular components fibrin(ogen) fragments, plasminogen and lipoprotein (a). Kinetic analysis demonstrates that CNBr-derived fibrinogen fragments completely protect plasmin from alpha 2AP. Plasminogen and 6-aminohexanoic acid decrease the rate of inhibition by 5- and 10-fold respectively. These studies show that CNBr-derived fibrinogen fragments and 6-aminohexanoic acid bind plasmin kringle(s) with binding constants of 2 micrograms/ml and 120 microM respectively, and that plasminogen binds to alpha 2AP with an affinity of 0.5 nM. The unmodulated inhibition is not effected by the presence of lipoprotein (a), but in the presence of protective CNBr-derived fibrinogen fragments the rate of inhibition is increased by the presence of the lipoprotein. The kinetics demonstrate that lipoprotein (a) binds to CNBr-derived fibrinogen fragments with an affinity of 4 nM, displacing plasmin from the protective surface. In addition, tissue-type plasminogen activator and trypsin inhibition by alpha 2AP is not slowed by the presence of CNBr-derived fibrinogen fragments or plasminogen (Pg), respectively. These kinetics suggest that the initial reversible interaction between plasmin and alpha 2AP is mediated by binding of the inhibitor to the kringle 1 domain of plasmin, with a reversible inhibition constant (Ki) of 5.0 x 10(-10) M. Under conditions where this kringle-inhibitor interaction is blocked, the reversible inhibition still occurs between the plasmin and alpha 2AP, but the initial Ki is increased to 5.0 x 10(-9) M. These data suggest that, in the circulation, plasmin inhibition by alpha 2AP may be down-regulated by fibrin, fibrin(ogen) fragments and Pg, but up-regulated by lipoprotein (a) in the presence of fibrin or fibrin(ogen) fragments. The lipoprotein (a)-mediated promotion of plasmin inhibition may provide an additional mechanism by which the lipoprotein impairs fibrinolysis and promotes atherosclerosis.
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PMID:Lipoprotein (a) promotes plasmin inhibition by alpha 2-antiplasmin. 138 85

Lipoprotein(a) [Lp(a)] is recognized as an independent risk factor for atherosclerosis. Lp(a) consists of a LDL-like moiety with an additional glycoprotein, apo(a), linked to apolipoprotein B-100. Apo(a) has a high homology with plasminogen (Pg). In vivo, Pg is activated on a fibrin surface by tissue Pg activator (tPA). We prepared Lp(a) from plasma by sequential ultracentrifugation followed by lysine-sepharose affinity chromatography. We found that a changing (donor dependent) fraction of the Lp(a) did not bind to lysine-sepharose. This fraction, designated Lp(a)lys-, was further purified using gel filtration. Bound Lp(a) [Lp(a)lys+] was eluted with 0.2 M EACA. Apo(a) isoforms in both fractions were identical. In contrast Lp(a)lys+ inhibited Pg activation by tPA in vitro (IC50% 20 mg/l), whereas Lp(a)lys- did not. In addition Lp(a)lys- did not bind to CNBr-digested fibrinogen whereas Lp(a)lys+ did (Kd, app = 0.2 nM). Therefore we conclude that a changing donor dependent fraction of human plasma Lp(a) does not inhibit Pg activation in vitro and does not bind to CNBr-digested fibrinogen.
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PMID:Lysine-binding heterogeneity of Lp(a): consequences for fibrin binding and inhibition of plasminogen activation. 141 65

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

Increasing evidence has indicated that the modulation of intracellular redox states has marked influence on cellular events such as proliferation, activation, growth inhibition and death via the regulation of intracellular signal transduction and gene expression. Thioredoxin(TRX) is a multifunctional stress-inducible protein which protects cells from various types of stresses. TRX shows not only scavenging activity for ROS, but also regulating activity for various intracellular molecules including transcription factors. Overexpression of TRX in transgenic mice attenuates adriamycin-induced cardiotoxicity by reducing oxidative stresses. We demonstrated that serum TRX levels are correlated with the severity of heart failure, and are negatively correlated with left ventricular ejection fractions in patients with heart failure. Moreover, we found that the serum TRX levels in patients with ACS were significantly higher than in SA, whereas no significant difference was found between patients with SA and control subjects. The expression of TRX is enhanced not only in endothelial cells and macrophages in the human atherosclerotic plaques, but also in balloon-injured rat arteries. These findings suggest that TRX and the redox system modulated by TRX play an important role in the cellular defense against oxidative stress in cardiovascular diseases including the progression of atherosclerosis.
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PMID:[Thioredoxin and atherosclerosis]. 1467 90

Longitudinal associations of malnutrition with atherosclerotic events in uremia are unclear. In 50,732 incident Medicare dialysis patients who had normal (18.5 to 24.9 kg/m(2)), low (<18.5 kg/m(2)), or high (> or = 25 kg/m(2)) body mass index (BMI) and initiated dialysis in the United States from January 1995 to December 1999 with reported measured creatinine clearances and acute coronary syndrome (ACS; International Classification of Diseases, Ninth Revision codes 410.x and 411.x) were examined in parametric survival models. Normal BMI was the referent group. Twenty-four-hour urinary creatinine (UCr) was used as a measure of muscle mass. There were 7213 (14.2%) hospitalized ACS events, 1528 (22%) of which were fatal (death within 30 d). One-year post-ACS mortality was 48%. Low BMI (hazard ratio [HR], 0.89; P = 0.02] was associated with lower hazard, and UCr was not predictive (NS) of hospitalized ACS in multivariable model. Low BMI (NS) was not associated with a composite end point of hospitalized ACS/suspected out-of-hospital ACS death, whereas lowest UCr quartile was associated with higher hazard (HR, 1.14; P < 0.001). Low BMI (HR, 1.24; P < 0.001) and decrease in UCr (highest quartile reference, second quartile HR, 1.11 [P < 0.001]; third quartile HR, 1.24 [P < 0.001]; and fourth quartile HR, 1.43 [P < 0.001]) were associated with increased hazard of death. Hospitalized ACS events in dialysis patients carry very high immediate and long-term mortality. Positive longitudinal associations of malnutrition with documented hospitalized ACS events could not be demonstrated. Further longitudinal studies are warranted to provide definitive evidence of malnutrition as a uremic risk factor for atherosclerosis.
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PMID:Malnutrition and atherosclerosis in dialysis patients. 1497 76

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

Recent evidence has suggested an association between Chlamydia pneumoniae infection and coronary atherosclerosis. A significant association has also been detected between heat shock protein (HSP) 60 antibody and the severity of coronary atherosclerosis. The aim of this study was to define the relationship between instability of ischemic heart disease (IHD) and serum levels of HSP60 and C. pneumoniae antibodies. Blood samples for the measurement of serum antibody titers were obtained from 1131 patients with ischemic heart disease (65+/-9 years; male/female, 828/303) and 127 non-IHD controls with normal coronary arteries (64+/-9 years; male/female, 60/67) on the day of cardiac catheterization. The serum levels of anti-human HSP60 IgG antibody and anti-chlamydial IgM, but not IgG or IgA, antibody were significantly higher in ACS patients than in stable IHD patients or controls. These results suggest that acute C. pneumoniae infection with HSP60-related immunological responses may contribute to the pathophysiology of acute coronary syndromes.
Atherosclerosis 2005 Nov
PMID:Acute Chlamydia pneumoniae infection with heat-shock-protein-60-related response in patients with acute coronary syndrome. 1621 93

During the past 2 decades, randomized trials have proved the efficacy of several treatments for non-ST-elevation acute coronary syndromes (NSTE-ACSs), including aspirin, beta blockers, and coronary revascularization. However, the cumulative effectiveness of these evolving therapies in actual clinical practice remains unknown. The Atherosclerosis Risk In Communities (ARIC) surveillance study uses rigorous prospective community surveillance to monitor the epidemiology of coronary heart disease among subjects who are 35 to 74 years of age and reside in 4 United States communities, with a population totaling 370,000 subjects. We identified 6,379 ARIC surveillance patients who were hospitalized with NSTE-ACS (defined as cardiac chest pain and ST depression or T-wave inversion on the presenting electrocardiogram) between 1987 and 2000 and then analyzed 30-day and 1-year mortalities by calendar year of admission. Using logistic regression, 30-day mortality was modeled first using predictor variables of the calendar year, ARIC community, and indicators of severity and co-morbidity and then by adding variables for treatment with aspirin, beta blockers, and coronary revascularization to this model. Crude 30-day mortality decreased from 8.6% in 1988 to 3.6% in 2000 (p for trend <0.001), a trend that remained significant (p = 0.006) after adjustment for case severity and co-morbidity. The trend became nonsignificant after adjustment for treatment variables, suggesting that newer treatments may explain the improved survival. In conclusion, 30-day mortality from NSTE-ACS has decreased as treatment has improved.
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PMID:Fourteen-year (1987 to 2000) trends in the attack rates of, therapy for, and mortality from non-ST-elevation acute coronary syndromes in four United States communities. 1627 76

Systemic factors and blood flow velocity related to atherosclerosis have been examined mainly separately or by in vitro studies. The aim of our study was to investigate the association between local coronary blood flow (corrected TIMI frame count, CTFC) and systemic atherosclerosis-related inflammatory parameters such as soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (Il-6), high sensitivity C-reactive protein (hsCRP) and von Willebrand factor (vWF) in humans. We enrolled the following groups of ischemic heart disease (IHD) patients: patients with coronary stenosis and stable (CAD, n = 96) or unstable angina (ACS, n = 27), patients with documented myocardial ischemia and normal coronary angiogram (NEG, n = 68). Patient groups showed only marginal differences in CTFC or sICAM-1 levels. In contrast, when IHD patients were studied individually, general positive correlation was found between CTFC and sICAM-1 level (r = 0.33; in NEG r = 0.25; in CAD r = 0.37; in ACS r = 0.61), being the strongest in ACS. The relation was independent from age, gender, BMI, smoking, hypertension, diabetes, previous myocardial infarction, family history of IHD, medication, hsCRP, IL-6 and vWF levels. (odds ratio, OR = 6.4; CI 95%: 2.43-16.84; p < 0.05). Nevertheless, correlation between CTFC and IL-6, hsCRP, vWF levels was not found. These results indicate inverse correlation between coronary blood flow and adhesion molecule production independently from conventional cardiovascular risk factors and inflammatory markers.
Atherosclerosis 2006 Sep
PMID:Inverse correlation between coronary blood flow velocity and sICAM-1 level observed in ischemic heart disease patients. 1629 92


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