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 molecular genetic defect of a female patient with apolipoprotein A-I (apoA-I) deficiency and premature atherosclerosis was examined. Her parents were first cousins. Her plasma density fraction from 1.063 to 1.21 g/ml contained no apoA-I on SDS/PAGE and no measurable high density lipoprotein cholesterol. Southern blot hybridization showed no gross abnormality to be present in the patient's apoA-I gene and homozygosity for a haplotype of restriction fragment length polymorphisms in the apoA-I gene region. Sequencing after amplification by PCR revealed a codon 84 nonsense mutation (CAG----TAG, Gln----stop) of exon 4 and a codon 67 missense mutation (GCC----ACC, Ala----Thr) of exon 3 in the patient's apoA-I gene. The data from dot-blot hybridization with allele-specific oligonucleotide probes indicated that she was homozygous for the apoA-I gene with regard to the two mutations. The codon 37 missense mutation was also detected in the apoA-I gene of 6 out of 60 controls, who all had normal levels of apoA-I and high density lipoprotein cholesterol, suggesting that the missense mutation is polymorphic and not associated with apoA-I deficiency. These findings indicate that homozygosity for the apoA-I gene with codon 84 nonsense mutation causes the deficiency of apoA-I and of high density lipoprotein cholesterol in the patient.
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PMID:Apolipoprotein A-I deficiency due to a codon 84 nonsense mutation of the apolipoprotein A-I gene. 190 17

High levels of low density lipoprotein (LDL) and its apolipoprotein B (apoB) are risk factors for atherosclerosis and myocardial infarction (MI). There is rich genetic polymorphism in apoB, first detected as the Ag allotypes of LDL, but today mostly examined at the DNA level. Genes contribute to the population variation in LDL and apoB levels and alleles in polymorphisms at the apoB locus are candidate genes with respect to control of lipid levels and susceptibility to atherosclerosis and MI. The XbaI polymorphism at the apoB locus, which involves the third base of threonin codon 2488 (ACC-->ACT) without changing the amino acid sequence was examined in a case-control study comprising 238 survivors of myocardial infarction (MI) and 621 controls. In univariate analysis, frequencies of genotypes in this polymorphism were not statistically different between patients and controls of either sex. However, in multivariate logistic regression analysis, the odds ratio X-X- homozygotes (homozygotes for absence of restriction site) for having MI compared to the pooled group of heterozygotes and X+X+homozygotes (homozygotes for presence of restriction site) was 2.16 (p = 0.007), after adjustments for age, sex, and levels of apoB, high density lipoprotein (HDL) cholesterol (HDLC) and Lp(a) lipoprotein. It appeared that heterozygotes do not have increased risk, compared to the X+X+ homozygotes. Stratification according to low or high levels of apoB, HDLC and Lp(a) lipoprotein, showed that the X-X- genotype was more common in patients than controls, in all subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:XbaI polymorphism in DNA at the apolipoprotein B locus is associated with myocardial infarction (MI). 790 11

According to the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), patients with low-density lipoprotein (LDL) cholesterol > or = 130 mg/dL should be discharged on lipid-lowering therapy. When LDL cholesterol levels are between 100 and 129 mg/dL, evaluation of ratios of LDL cholesterol/high-density lipoprotein (HDL) cholesterol or total cholesterol/HDL cholesterol may provide additional insight into a patient's risk status. Patients who were using statin therapy before admission for an acute coronary syndrome should be continued on lipid-lowering therapy. The American College of Cardiology/American Heart Association (ACC/AHA) 2002 guideline update for management of patients with unstable angina and non-ST-segment elevation myocardial infarction recommends statin therapy at discharge as a class I indication, level of evidence A. Furthermore, studies confirm that statin therapy begun early during hospitalization can prevent ischemic events in patients who are treated by an invasive strategy and those who are treated only by a medical strategy. However, studies suggest that patient compliance with a statin regimen after discharge is far from optimal. There are 2 programs available to help ensure that appropriate patients receive and continue taking lipid-lowering therapy. These programs are the Cardiac Hospitalization Atherosclerosis Management Program (CHAMP) and the Guidelines Applied in Practice (GAP).
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PMID:Optimizing lipid management in patients with acute coronary syndromes. 1261 96

This paper intends to make an update of recent publications and guidelines for evaluation in coronary symptom-free patients undergoing vascular surgery. It emphasizes the role of preoperative clinical evaluation that should identify the most appropriate testing, and treatment strategies to optimize care of the patient and avoid unnecessary testing in this era of cost containment. Selective preoperative coronary artery disease screening and revascularization achieve excellent perioperative and late results after high-risk vascular surgery. Supplemental preoperative evaluation is discussed (exercise ECG, stress echocardiography and stress tomoscintigraphy). Asymptomatic patients with good functional capacity can undergo intermediate-risk surgery without further non-invasive testing. Conversely, further noninvasive testing is often considered for patients with poor functional capacity or moderate functional capacity but higher-risk surgery especially for patients with 2 or more intermediate risk predictors. Additional testing may be considered on an individual basis for patients without clinical markers but with poor functional capacity prior to vascular surgery, particularly those with several minor clinical risk predictors. Because of a higher prevalence of silent myocardial ischaemia in diabetes mellitus, these patients require specific care. Until further data are available, indications for myocardial revascularization in the perioperative setting are similar to those in the ACC/AHA guidelines for use of myocardial revascularization in general. General practitioners, cardiologists, angiologists, vascular surgeons and anaesthesiologists should collaborate and aim to slow down the progression of atherosclerosis by giving their patients an optimum secondary cardiovascular prevention.
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PMID:Evaluation, severity and prognostic significance of silent myocardial ischaemia in vascular patients. 1291 58

Non-invasive quantitative indices of atherosclerosis are promising new parameters for an improved prognostic stratification of patients with risk factors that aim at individualized risk factor assessment and modification. In a recently published ACC/AHA consensus document, further data on the diagnostic and prognostic value of coronary calcified plaque quantification were strongly encouraged prior to its use in the general population. In this present work we summarize data published since, which contribute significantly to the prognostic value of fast CT-based noninvasive coronary calcified plaque quantification. It is a measure of atherosclerostic disease activity and is hence an index for the likelihood of future cardiovascular events. Current data indicate that noninvasive quantification of coronary atherosclerosis has incremental prognostic value beyond conventional single risk factor assessment. However, it is not clear yet whether it has a significant value beyond quantitative combined risk assessment using complex risk prediction models such as Framingham charts. Results from ongoing prospective trials such as the MESA study in the US and the Heinz Nixdorf Recall study in Germany will clarify some of the pending issues. In addition, it is still unclear, at what stage of the disease process, which of the available imaging tools will provide optimal diagnostic and prognostic value for the individual patient.
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PMID:[Prognostic value of noninvasive coronary plaque burden quantification in patients with risk factors]. 1296 26

Ischemic heart disease is one of the leading causes of death in Japan. Acute coronary syndrome (ACS) most commonly begins with atherosclerotic plaque rupture and intracoronary thrombus formation. Therefore, the primary goal of treatment of acute coronary occlusion is the achievement of early and complete reperfusion. To achieve this goal, detection of atherosclerosis and/or myocardial necrosis by imaging and serologic tests is important. Original diagnosis of acute myocardial infarction (AMI) was made from typical symptoms, characteristic rises in serum enzyme levels, and an atypical electrocardiographic pattern. Increasingly sensitive and specific tests have been developed in recent years and have been rapidly adopted into clinical practice. Rapid developments in technology in the field of serum biomarkers have redefined the diagnosis of AMI. The new ESC/ACC criteria place increased emphasis on cardiac biomarkers, especially troponins. However, the electrocardiogram still remains significant in the diagnosis of AMI and the ability to identify high risk subgroups by admission electrocardiogram is necessary to estimate the severity of AMI. Current practice guidelines recognize the importance of promptly restoring normal epicardial blood flow, but blood flow to the ischemic tissue may still be impeded after relief of the occlusion; a phenomenon known as no reflow. Myocardial scintigraphy is one of the methods for defining coronary microvascular injury in the acute phase of AMI. Prompt assessment of coronary perfusion and detection of coronary microvascular injury may aid in making decisions concerning the use of drugs to improve microvascular function and left ventricular function after primary coronary angioplasty.
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PMID:[Ischemic heart disease]. 1596 7

Pathological hypoxia plays an important role in many diseases, such as atherosclerosis, cancer, and rheumatoid arthritis. The aim of the present study was to examine the effects of different statins on hypoxia-induced endothelial cell signalling. Human umbilical cord vein endothelial cells (HUVEC) were treated with NaCN (CN, 2.5 mmol/l) to simulate a transient hypoxia. The CN-induced increase of endothelial cell numbers was significantly (n = 10, p < 0.01) reduced by the Ca(2+) chelator BAPTA (10 micromol/l), or the reactive oxygen species (ROS) scavenger N-acetylcysteine (ACC, 1 mmol/l), or the NAD(P)H-oxidase inhibitor diphenyleneiodonium (DPI, 5 micromol/l). In detail, cell numbers were (in percentage of control): 163.24 (CN), 90.06 (CN+ACC), 92.06 (CN+DPI). Intracellular-Ca(2+) and -ROS, analysed by fluorescence imaging, were significantly increased by CN. Interestingly, the CN-induced increase of ROS was in part Ca(2+)-dependent, whereas the Ca(2+) increase was not ROS-dependent. Simvastatin (5 micromol/l), fluvastatin (2.5 micromol/l), and cerivastatin (0.1 micromol/l) all reduced CN-induced proliferation, ROS generation and Ca(2+) increase. Cell viability was not reduced by the statins and the antiproliferative effect was completely reversed by mevalonate (500 micromol/l). In conclusion our study demonstrates that statins block hypoxia-associated endothelial proliferation by preventing the increase of Ca(2+) and ROS.
Atherosclerosis 2006 Apr
PMID:Statins inhibit hypoxia-induced endothelial proliferation by preventing calcium-induced ROS formation. 1611 21

Pharmacological therapy for acute coronary syndrome (ACS) is divided into the treatment for myocardial ischemia and that for coronary thrombosis. Immediate nitrates(sublingual tablets and sprays) are used to alleviate attacks and patients not responding them are treated by intravenously in 24 hours. The initial treatment for non-ST-segment elevation myocardial infarction(NSTEMI) with the administration of nitrates and beta blocker is judged as Class I (evidence level B) by ACC/AHA classification. Administering beta blocker in patients with ACS has reduced the progression to myocardial infarction by 13%. Ca antagonist is administered in patients for whom nitrates and/or beta blocker are contraindicated or in whom myocardial ischemia persists or frequently relapses in spite of the treatment with an adequate dose of the drugs. Since recent studies have suggested that ACS may not result from a local vascular stenosis, but from coronary inflammation, treating the local vascular lesion alone with PCI is not enough. Rather, pharmacological therapy is important to reduce overall patient risk, thereby suppressing the progress of atherosclerosis.
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PMID:[Anti-anginal medication in management of acute coronary syndrome]. 1661 94

Interleukin-6 (IL-6) is associated with many disease states in humans. We prospectively sought to determine whether IL-6 levels increased following percutaneous coronary intervention (PCI) in the absence of myonecrosis. Additionally, we systematically assessed other clinical and anatomic factors associated with IL-6 levels in a population of patients with coronary atherosclerosis undergoing PCI. Blood samples were collected from 117 patients at baseline, 8 and 16 h following PCI. Samples were assayed for IL-6, creatine kinase-myocardial band (CK-MB), troponin-I (Tn-I), high sensitivity C-reactive protein, glucose, haemoglobin A1c, and a lipid profile. Genotyping of the -174G-->C polymorphism of the IL-6 gene was performed. IL-6 levels increased following PCI among the study group (slope = 0.4 pg/mL/h, P = 0.001). IL-6 levels increased to a similar degree in the absence of myonecrosis. Patients with the XC genotype (either having the GC or the CC allele) had higher IL-6-values at baseline compared to GG genotype patients (4.9 +/- 6.4 vs. 2.6 +/- 1.8 pg/mL, P = 0.02). Multivariable predictors of detectable baseline IL-6 levels included XC genotype (odds ratio [OR]: 4.14, 95% CI 1.58-10.82, P = 0.004), ACC/AHA type C lesion classification (OR: 4.08, 95% CI 1.54-10.84, P = 0.005), elevated baseline Tn-I (OR: 3.31, 95% CI 1.16-9.43, P = 0.025), diabetes (OR: 3.00, 95% CI 1.11-8.09, P = 0.030), and waist circumference (OR: 1.49, 95% CI 1.08-2.06, P = 0.015). Predictors of peak IL-6 following PCI included the XC genotype (estimate 1.4, 95% CI 1.06-1.87, P = 0.019), homeostasis model assessment (estimate 0.99, 95% 0.982-0.999, P = 0.042) and baseline Tn-I > upper limit of normal (estimate 0.7, 95% CI 0.50-0.96, P = 0.039). Lastly, IL-6 increased following PCI even in the absence of myonecrosis as measured by Tn-I elevation. IL-6 levels are also related to the -174G-->C polymorphism, arterial injury, lesion complexity, and insulin resistance.
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PMID:Increase in interleukin-6 following arterial injury is related to insulin resistance, the -174G-->C polymorphism and complex plaque morphology. 1698 79

The Leu33Pro polymorphism of the gene encoding beta(3) integrin (ITGB3) is associated with acute coronary syndromes and influences platelet aggregation. Three common promoter polymorphisms have also been identified. The aims of this study were to (1) investigate the influence of the ITGB3 -400C/A, -425A/C and -468G/A promoter polymorphisms on reporter gene expression and nuclear protein binding and (2) determine genotype and haplotype associations with platelet alpha(IIb)beta(3) receptor density. Promoter haplotypes were introduced into an ITGB3 promoter-pGL3 construct by site directed mutagenesis and luciferase reporter gene expression analysed in HEL and HMEC-1 cells. Binding of nuclear proteins was assessed by electrophoretic mobility shift assay. The association of ITGB3 haplotype with platelet alpha(IIb)beta(3) receptor density was determined in 223 subjects. Species conserved motifs were identified in the ITGB3 promoter in the vicinity of the three polymorphisms. The GAA, GCC, AAC, AAA and ACC constructs induced approximately 50% increased luciferase expression relative to the GAC construct in both cell types. Haplotype analysis including Leu33Pro indicated five common haplotypes; no associations between ITGB3 haplotypes and receptor density were found. However, the GCC-Pro33 haplotype was associated with significantly higher vWF activity (128.6 [112.1-145.1]%) compared with all other haplotypes (107.1 [101.2-113.0]%, p=0.02). In conclusion, the GCC-Pro33 haplotype was associated with increased vWF activity but not with platelet alpha(IIb)beta(3) receptor density, which may indicate ITGB3 haplotype influences endothelial function.
Atherosclerosis 2008 Jun
PMID:Beta3 integrin haplotype influences gene regulation and plasma von Willebrand factor activity. 1804 6


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