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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several studies suggest that inflammation plays an important role in the pathogenesis of diabetes mellitus, as well as atherosclerosis, and acute-phase reactants have been proposed as monitors for the ongoing process of these diseases. We studied the clinical significance of serum high-sensitivity C-reactive protein (hs-CRP) in relation to chronic diabetic complications using 114 Japanese patients with Type 2 diabetes mellitus. The hs-CRP values were normalized by logarithmic transformation for statistical analysis. Retinopathy and hypertension were extracted as significant modulators for the hs-CRP value in the diabetic patients, in addition to previously known factors, age, and body mass index (BMI), by multivariate analysis. The hs-CRP level in normotensive diabetic patients without retinopathy was not significantly different from that of normal control participants after adjustment for age and BMI. The hs-CRP value was significantly high in the patients with hypertension, despite the existence or absence of diabetes. On the other hand, the hs-CRP level of the diabetic patients complicated with retinopathy was low especially in those with hypertension. The frequency of patients having an hs-CRP value above 1.0 mg/l who are thought to be at risk for cardiovascular diseases was also high in the patients complicated with hypertension and low in the diabetic patients with retinopathy. These results indicate that the presence or absence of hypertension and retinopathy should be taken into consideration for the interpretation of the serum hs-CRP in diabetic patients.
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PMID:Retinopathy and hypertension affect serum high-sensitivity C-reactive protein levels in Type 2 diabetic patients. 1586 55

Type 2 diabetes carries a 2-6-fold increased risk of cardiovascular disease (CVD) and death. Indeed, the risk of major cardiovascular events in Type 2 diabetic patients without history of coronary heart disease (CHD) is equivalent to that observed in non-diabetic subjects with CHD. However, atherosclerosis may also precede the development of diabetes, suggesting that both disorders share common genetic and environmental antecedent factors ("common soil" hypothesis). One such a possible ancestor is insulin resistance which constitutes both a major feature of Type 2 diabetes and an independent risk factor for CHD. It is well documented that inflammatory processes play an important role in the causation of atherosclerotic CVD. Inflammatory mediators play a paramount role in the initiation, progression, and rupture of atherosclerotic plaques. Thus, markers of inflammation and endothelial dysfunction may provide additional information about a patient's risk of developing CVD and may become new targets for treatment. On the other hand, evidence has emerged suggesting that inflammation is also involved in the development of Type 2 diabetes. Prospective studies have demonstrated that increased levels of pro-inflammatory markers such as CRP or reduced levels of anti-inflammatory markers such as adiponectin predict the development of Type 2 diabetes. Thus, there is accumulating evidence suggesting that inflammation is the bridging link between atherosclerosis and the metabolic syndrome. Interventions by lifestyle modification or agents with anti-inflammatory properties may reduce the risk of both conditions. Drugs exerting anti-inflammatory and vascular effects have future potential to be used within an array of interventions aimed at reducing the enormous cardiovascular burden associated with Type 2 diabetes.
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PMID:Type 2 diabetes as an inflammatory cardiovascular disorder. 1589 50

To date, there has been no convincing evidence for an association between Chlamydia pneumoniae or Helicobacter pylori and ectasia. In this case-control study, we have investigated the association of H. pylori and C. pneumoniae seropositivity with ectasia, severe coronary atherosclerosis, and normal vessels, which were so classified by coronary angiography. We have also evaluated the influence of these infections on inflammatory markers such as high-sensitive C-reactive protein (hsCRP) and interleukin 6 (IL-6). Of the 796 patients undergoing coronary angiography for suspected ischemic heart disease, 244 patients were recruited. Of these, 91 had normal vessels, 88 had 3 or more obstructed vessels, and 65 had ectatic vessels without atherosclerosis. Eighty-seven atherosclerotic patients (98.9%) were positive for C. pneumoniae IgG, as were 64 ectatic patients (98.5%) and 76 controls (83.5%) (P < 0.001). Forty-two atherosclerotic patients (47.7%) were positive for C. pneumoniae IgM, as were 43 ectatic patients (66.2%) and 43 controls (47.3%) (P = 0.036). Seventy-two atherosclerotic patients (81.8%) were positive for H. pylori IgA, as were 26 ectatic patients (40.0%) and 44 controls (48.4%) (P < 0.001). High-sensitive CRP levels were significantly higher in ectatic patients (5.639 mg/L) than in controls (4.390 mg/L) (P = 0.032), and IL-6 levels were significantly higher in atherosclerotic patients (33.92 U/L) than in controls (14.01 U/L) (P < 0.001). Interleukin-6 levels were higher in H. pylori seropositive patients, and hsCRP levels were higher in C. pneumoniae seropositive patients, when compared with seronegatives. We suggest that, as in atherosclerosis, C. pneumoniae infection is related to ectasia, with raised CRP levels.
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PMID:Ectasia and severe atherosclerosis: relationships with chlamydia pneumoniae, helicobacterpylori, and inflammatory markers. 1590 17

Plasma concentration of high sensitive C-reactive protein (hsCRP) is used as a marker for inflammatory states and is directly correlated with the risk for coronary heart disease. Evidence concerning the role of inflammation in atheroma formation has been derived from several models of atherosclerosis. Inflammation should exert its adverse vascular effects by structural changes in the artery wall and consequently alterations in arterial elasticity, which could be detected already in asymptomatic early vascular disease. We hypothesized that CRP is related to large artery elasticity, but not to small artery elasticity in early vascular disease. Therefore, we examined the association between arterial stiffness of large and small arteries and inflammation in an asymptomatic population referred for primary prevention cardiovascular screening. Studies were performed in 391 subjects (age 21-82 years; 254 men, 137 women) who underwent screening at the Cardiovascular Disease Prevention Center. Large artery (C1) and small artery (C2) elasticity indices were obtained by the CVProfiler 2000 (HDI, Eagan, MN, USA). After overnight fasting, venous samples were taken for measurement of hsCRP, lipids, glucose. There was a significant inverse correlation between hsCRP (0.29 +/- 0.40 mg/dl) and C1 (16.7 +/- 5.8 ml/mmHg), r = -0.133, P = 0.01; there was no significant correlation between hsCRP and C2 (6.6 +/- 3.2 ml/mmHg). C2, but not hsCRP, was inversely correlated with age, abnormal lipids and glucose, whereas C1, but not hsCRP, was inversely correlated with age and systolic blood pressure (SBP). In multiple regression analysis, the relationship between hsCRP and C1 was not affected by age, body mass index, SBP, serum glucose or lipids. In conclusion, these findings support the hypothesis that hsCRP, a marker for acute and low-grade inflammation, is associated with large artery but not with small artery elasticity in asymptomatic individuals undergoing primary prevention cardiovascular screening.
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PMID:Relationship between C-reactive protein and arterial stiffness in an asymptomatic population. 1590 93

Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by a polyarticular joint inflammation which eventually leads to joint destruction and general disability. Besides these polyarticular manifestations, several systemic immune phenomena have been described. An increased mortality in RA patients is evident and is mainly caused by an increased cardiovascular risk. The correlation between disease activity and mortality highlighted the important role of the systemic inflammatory reaction in induction and progression of vascular damaging processes. Endothelial dysfunction and vascular inflammation are important, mechanisms in atherosclerosis and induced by conventional risk factors and systemic inflammation. It has been shown that the deleterious influence of conventional risk factors is aggravated by inflammatory mediators, mainly by pro-inflammatory cytokines. In addition, certain inflammatory mediators exert damaging effects to blood vessels. Especially CRP, merely considered as a risk indicating parameter in the past, has attracted remarkable attention. Also certain RA specific immune phenomena are of considerable proatherosclerotic potential. At least in part, they could be responsible for the excess mortality in RA patients. The newer TNFalpha blocking agents interfere with different mechanisms responsible for induction and perpetuation of atherosclerotic processes. Time will show whether they make a remarkable impact on the cardiovascular mortality in RA patients.
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PMID:[Cardiovascular manifestations in rheumatoid arthritis]. 1590 82

Advanced glycation end-products (AGEs), a group of carbohydrate-derived compounds formed by non-enzymatic glycation and oxidation, are markedly elevated in end-stage renal disease (ESRD) and may be related to both inflammation and oxidative stress. The cellular effects of AGE are largely mediated by their interaction with specific surface receptors, such as RAGE. Measurements of biomarkers of inflammation and oxidative stress were conducted in 7 hemodialysis (HD) patients (5 males) with persistent high-grade inflammation (C-reactive protein [CRP]>10 mg/L) and 11 HD-patients (6 males) with low-grade inflammation (CRP<10 mg/L) for at least 6 months. Measured biomarkers for inflammation included hs-CRP, interleukin (IL)-6, white blood cells, neutrophils, S-albumin, peroxisome proliferator-activated receptors (PPAR alpha, beta, gamma) and nuclear factor kappaB (NFkappaB) activity. Markers for oxidative stress were advanced oxidation products (AOPP), myeloperoxidase (MPO)-activity, pentosidine and carboxymethyl lysine (CML). In addition, the effect of increasing doses of CML-modified human serum albumin on NFkappaB activity was tested in mononuclear cells isolated from each patient. As expected, HD-patients with high-grade inflammation had significantly elevated levels of IL-6 (median 9.2 pg/mL versus 2.5 pg/mL; p<0.01), MPO-activity (134.5+/-14.6 DeltaOD(630)/(min mg protein) versus 80.5+/-12.9 DeltaOD(630)/(min mg protein); p<0.05), PPAR-gamma (0.65+/-0.01 OD(655) versus 0.56+/-0.01 OD(655); p<0.01), and AOPP (269+/-54 microM versus 163+/-15 microM; p<0.05) compared with low-grade inflamed patients. Significant associations were demonstrated between hs-CRP and NFkappaB (rho=0.58; p<0.05), AOPP (rho=0.49; p<0.05) and PPAR-gamma (rho=0.62; p<0.05), respectively. In the patient group with high-grade inflammation, stimulation of mononuclear cells with CML-modified human serum albumin caused a rapid dose-dependent rise (p<0.0001) in NFkappaB activity that could be completely blocked by an anti-RAGE antibody. Inflammation and oxidative stress biomarkers are interrelated in ESRD. Inflammatory cell signal pathways, such as NFkappaB, are activated by CML-modification of proteins via RAGE.
Atherosclerosis 2005 Jun
PMID:Enhanced RAGE-mediated NFkappaB stimulation in inflamed hemodialysis patients. 1591 Aug 60

Atherosclerosis is a chronic inflammatory disease associated with an elevation of inflammatory markers such as CRP -- a robust predictor of cardiovascular events. Inflammation also plays a pivotal role in the pathogenesis of osteoporosis. IL-6 proved to be the most important predictor of bone loss in the proximal femur. Adipocyte-produced inflammatory cytokines are the pathogenetic link between obesity and its metabolic consequences. The different components of the metabolic syndrome are at the same time well-established risk factors for osteoporosis. Physical training, weight loss, and a Mediterranean-style diet all have a proven cytokine-lowering effect. Contrary to muscle mass, adipose tissue if at all contributes only marginally to the preservation of bone. As a consequence, increasing lean body mass while reducing fat mass seems to be the most effective way to prevent both atherosclerosis and osteoporosis.
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PMID:[Obesity and osteoporosis]. 1591 26

The narrow therapeutic window of the immunosuppressive drug cyclosporine (CsA), the interindividual variability of its metabolism, and the immunosuppressive activity/toxicity of some metabolites require investigation to correlate the parent substance and its metabolites and observed clinical parameters. Improved knowledge about these correlations may improve postoperative treatment of transplant patients. To observe such correlation therapeutic drug monitoring was performed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) on 202 blood samples of kidney transplant patients. As CsA and its metabolites are preferably bound to lipoproteins in vivo, sample preparation included protein precipitation, solid phase extraction, and separation on a reversed phase column. Mass-spectrometric detection by an electrospray ionization chamber made the detection and quantification of the sodium adducts of CsA and its metabolites AM1, AM1c, DihydroAM1, AM19, and AM4N possible. With the presented HPLC-MS method, rapid information was achieved about the specific metabolization in a patient. Statistical computations related CsA and its metabolite concentrations to clinically important blood parameters. Significant correlation to the blood level of bilirubin and liver enzymes confirmed the presumed hepatotoxic potential of CsA and some metabolites. Furthermore, a strong correlation of AM19 to CRP and IL6 was observerd. These parameters may influence the prognosis for atherosclerosis, inflammation, and chronic allograft nephropathy.
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PMID:Determination of cyclosporine and its metabolites in blood via HPLC-MS and correlation to clinically important parameters. 1591 51

The relationship between humoral immunity to hsp60 and type 2 diabetes along with other relevant metabolic, inflammatory and immunogenetic variables was studied in 76 non-diabetic and 74 diabetic persons aged 55-74 years selected from the population-based KORA Survey 2000. Antibodies to human hsp60 were measured in serum samples by ELISA. Hsp60 antibodies were detected in all but two individuals in a considerable range of titres (22-1,856 AU/ml). There was no significant association to age and sex, or to key clinical or metabolic parameters (BMI, WHR, HbA1c, total cholesterol, LDL cholesterol, HDL cholesterol, systolic and diastolic blood pressure, albumin, uric acid) or immunological parameters (CRP, IL-6, sIL-6R, TNFalpha, sTNFalpha R60, sTNFalpha R80). Analysis of antibody-positive individuals revealed an association between hsp60 antibodies and diabetes at borderline significance (p = 0.047), which was lost when the two antibody-negative individuals were included. Genetic analyses indicated that this association was significant in carriers of the C allele of the IL-6 promoter region polymorphism at nucleotide -174 (p = 0.02), but not in GG genotype carriers. We conclude that humoral immunity to human hsp60 may be enhanced in those diabetic patients carrying the -174C allele of the IL-6 gene. This finding may contribute to an understanding of the relationship between the -174C allele and increased risk of atherosclerosis.
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PMID:Association of humoral immunity to human Hsp60 with the IL-6 gene polymorphism C-174G in patients with type 2 diabetes and controls. 1595 88

Disturbances in nitric oxide (NO) metabolism resulting in endothelial dysfunction play a central role in the pathogenesis of atherosclerosis in hypercholesterolemia and in individuals with type 2 diabetes. It is unclear whether lipid lowering therapy with HMG-CoA-reductase inhibitors might improve endothelial function in subjects with type 2 diabetes as it is demonstrated in non-diabetic subjects with hypercholesterolemia. We examined the influence of 0.2 mg and 0.8 mg cerivastatin on endothelial function in a multicenter, randomised, double-blind, and three-arm placebo-controlled clinical trial. Endothelial function was assessed by nitric oxide-dependent flow mediated vasodilatation (FMD) of the brachial artery. A total of 103 patients with type 2 diabetes were enrolled in the study. Bayer Company undertook a voluntary action to withdraw cerivastatin from market, therefore the study was terminated earlier. At this point 77 patients were randomised, of which 58 completed the study (mean age 60 +/- 8 years, HbA1c 7.4 +/- 0.9 %). At baseline mean FMD was disturbed in all three therapy arms (5.18 +/- 2.31 % in the placebo group, 3.88 +/- 1.68 in the 0.2-mg cerivastation group, and 4.86 +/- 2.25 in the 0.8-mg cerivastatin group). Despite a significant reduction in cholesterol and LDL-cholesterol-levels after 12 weeks of treatment (decrease in LDL-cholesterol - 26.8 +/- 13.9 % in the 0.2-mg group and - 40.3 +/- 16.0 % in the 0.8-mg group, p = 0.0001, ANCOVA) there was no difference in flow mediated vasodilatation (p = 0.52 and p = 0.56 vs. placebo, respectively, ANCOVA). HbA1c, CRP, and HDL-cholesterol did not change during the study. Furthermore no difference in safety profile between cerivastatin and placebo was found. Despite a significant improvement in lipid profile under statin therapy, no improvement of endothelial dysfunction in terms of nitric oxide bioavailability could be detected.
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PMID:Intense cholesterol lowering therapy with a HMG-CoA reductase inhibitor does not improve nitric oxide dependent endothelial function in type-2-diabetes--a multicenter, randomised, double-blind, three-arm placebo-controlled clinical trial. 1597 99


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