Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The homozygous deletion allele of the angiotensin converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the epsilon4 allele of the apolipoprotein E gene (apoE/epsilon4) are reported to be associated with ischemic heart disease. Cerebrovascular disease (CVD) is another atherosclerotic disease; and the effects of these polymorphisms on CVD have been confusing. In this study, we investigated whether ACE/DD, AGN/TT, and apoE/epsilon4 genotypes are associated with CVD and whether genetic risk is enhanced by the effect of one upon another. We ascertained these genotypes in patients with cerebral infarction (n = 55) and cerebral hemorrhage (n = 38), diagnosed by brain computed tomography. Control subjects for the infarction group and the hemorrhage group were randomly selected from 583 subjects matched for age, gender, and history of hypertension with patients. Frequency of ACE/DD genotype was higher in the patients with infarction than in the controls (chi2 = 6.1, P < .05). The AGN/TT genotype was not associated with either infarction or hemorrhage, but it increased the relative risk for cerebral infarction in the subjects with ACE/DD genotype (chi2 = 8.0, P < .01, odds ratio; 11.7, 95% confidence intervals: 1.4 to 96.0). There was no significant association between apoE/epsilon4 and CVD. These results suggest that ACE/DD predicts cerebral infarction, but not cerebral hemorrhage, and that AGN/TT enhances the risk for cerebral infarction associated with ACE/DD.
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PMID:Polymorphism of angiotensin converting enzyme, angiotensinogen, and apolipoprotein E genes in a Japanese population with cerebrovascular disease. 944 75

The authors studied the activity of cholesterol esters transport (CET), concentrations of apolipoprotein E in the blood and high density lipoproteins (HDLP) in parallel with other parameters of lipoprotein metabolism in 79 males and 62 females. 122 of them had ischemic heart disease (IHD) and primary hyperlipoproteinemia (HLP). 19 healthy controls were normolipidemic. Activation of CET and relative lowering of apoE content in HDLP with relevant increase in lipoproteins containing apoB were seen only in type IIB HLP. CET activity in controls was related to a significant positive correlation with concentrations of both cholesterol (CS) and CS esters (CSE) in HDLP and HDLP3 and negative correlation with the proportion free CS/CSE in HDLP. Opposite to normolipidemic subjects, in type IIB HLP there was a negative relationship between CET activity and HDLP3 CS level and positive--between free CS/CSE in HDLP but not with concentration of CSE and total CS in HDLP. In type IIA HLP patients no relationships were registered between CET activity and HDLP content of total CS and CSE as well as with HDLP3 CS level. In type IIB HLP a significant correlation was found between level of HDLP CS and CET activity. Concentration of apoE in HDLP correlated with apoB level in the serum but not with quantity of HDLP CS. Patients with type IIA HLP exhibited a significant negative correlation between CET activity and HDLP apoE. These patients had no dependence of CET activity on HDLP CS but had positive correlation between HDLP apoE and HDLP CS in the serum. Thus, defects of reverse CS transport may be induced not only by changes in CET activity but also by apoE distribution among lipoproteins of different classes.
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PMID:[Apolipoprotein E and activity of cholesterol esters transport in type IIA and IIB hyperlipoproteinemia]. 950 30

The proposition that environmental agents, such as diet, aluminum, and viruses, are as important as genetic factors in the etiology of Alzheimer's disease (AD) was advanced by the authors at the Challenging Views of Alzheimer's Disease meeting held in Cincinnati on July 28 and 29, 2001. Diet, dietary fat, and to a lesser extent, total energy (caloric intake), were found to be significant risk factors for the development of AD in a dozen countries, while fish consumption was found to be a significant risk reduction factor. An acid-forming diet, such as one high in dietary fat or total energy, can lead to increased serum and brain concentrations of aluminum and transition metal ions, which are implicated in oxidative stress potentially leading to the neurological damage characteristic of AD. Many of the risk factors for AD, such as cholesterol and fat, and risk reduction factors, such as whole grain cereals and vegetables, are shared with ischemic heart disease. Aluminum may cause neurological damage and a number of studies have linked aluminum to an increased risk for developing AD. The evidence for viral agents playing a role in AD is the strong association between the presence of HSV1 in brain and carriage of an apoE-epsilon4 allele in the case of AD patients but not of controls; statistical analysis shows the association is causal. Diet, aluminum, and viral infections may increase the prevalence of AD by eliciting inflammation, which may cause the neurological damage that results in AD.
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PMID:The significance of environmental factors in the etiology of Alzheimer's disease. 1222 37

The homozygous deletion allele of the angiotensin-converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the epsilon4 allele of the apolipoprotein E gene (apoE/epsilon4) are reported to be associated with ischemic heart disease. Cerebral infarction (CI) is another atherosclerotic disease, and the effects of these polymorphisms on CI have been confusing. The frequency of the DD genotype of the ACE gene, but not the TT genotype of the AGN gene and the epsilon4 allele of ApoE, was significantly higher in subjects with than those without CI in Japan. In this study, we investigated whether ACE/DD, AGN/TT, and apoE/epsilon4 genotypes are associated with CI and whether genetic risk is enhanced by the effect of one upon another. We ascertained these genotypes in patients with CI (n = 365), diagnosed by brain computed tomography. Control subjects for the infarction group were randomly selected from 319 subjects matched for age, gender, and history of hypertension with patients. The ACE/DD genotype was not associated with CI. Frequency of the AGN/TT genotype was higher in patients with CI than in controls (chi2 = 12.287, p < 0.05). The frequency of t allele was 0.88 in patients and 0.82 in controls (chi2 = 11.041, p < 0.05; odds ratio, 1.7). Furthermore, the AGN/TT genotype increased the relative risk for CI in subjects with the ACE/DD genotype (chi2 = 7.8, p < 0.05; odds ratio, 1.9). There was no significant association between apoE/epsilon4 and CI. These results suggest that AGN/TT predicts CI and ACE/DD enhances the risk for CI associated with AGN/TT in a Korean population.
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PMID:Polymorphism of angiotensin-converting enzyme, angiotensinogen, and apolipoprotein E genes in Korean patients with cerebral infarction. 1450 Sep 90

Common alleles of the apolipoprotein-E gene (APOE) are associated with different risks of ischemic heart disease, Alzheimer's disease, and other chronic conditions in European populations. Also, the APOE allele frequencies vary widely among European countries. We estimated the proportion of differences in mortality and differences in life span that are attributable to differences in APOE allele frequencies in Europe. Mortality rates by age, sex, and APOE genotype for six countries (Denmark, Finland, France, Italy, the Netherlands, and Sweden) were used to standardize mortality rates to the allele frequencies in Italy. Differences in APOE allele frequencies explain 12%-17% of the variation among these countries in mortality in people older than 65 years and 1%-2% of the variation in life span in those older than 65 years. Differences by genotype in mortality in people older than 15 years account for about 3.5% of the genetic contribution to the variation in life span in Denmark.
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PMID:The APOE gene and differences in life expectancy in Europe. 1471 82

1. Phospholipid metabolites lysophospholipids cause extracellular K(+) accumulation and action potential shortening with increased risk of arrhythmias during myocardial ischemia. Here we studied effects of several lysophospholipids with different lengths of hydrocarbon chains and charged headgroups on HERG K(+) currents (I(HERG)) expressed in HEK293 cells and the potential mechanisms using whole-cell patch-clamp techniques. 2. Only the lipids with 16 hydrocarbons such as 1-palmitoyl-lysophosphatidylcholine (LPC-16) and 1-palmitoyl-lysophosphatidylglycerol (LPG-16) were found to produce significant enhancement of I(HERG) and negative shifts of HERG activation, although the voltage dependence of the effects was different between LPC-16 and LPG-16 which have differently charged headgroups. The lipid with 18 hydrocarbons modestly increased I(HERG). The lipids with 6 or 24 hydrocarbons had no effect or slightly decreased I(HERG). 3. Inhibition or activation of protein kinase C did not alter the effects of LPC-16 and LPG-16. Participation of phosphatidylinositol-4,5-bisphosphate in I(HERG) enhancement by LPC-16/LPG-16 was also excluded. 4. Vitamin E augmented the effects of LPC-16/LPG-16 whereas xanthine/xanthine oxidase reduced I(HERG): indicating that LPC-16/LPG-16 produced dual effects on I(HERG): direct enhancement of I(HERG) and indirect suppression via production of superoxide anion. 5. We conclude that enhancement of HERG function by lysophospholipids is specific to the lipids with 16-hydrocarbon chain structure and the pattern of voltage dependence is determined by the polar headgroups. The increase in I(HERG) is best described by direct interactions between lipid molecules and HERG proteins, which is consistent with lack of effects via membrane destabilization or modulation by intracellular signaling pathways.
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PMID:Potential mechanisms for the enhancement of HERG K+ channel function by phospholipid metabolites. 1474 14

The aim of the study was to specify postprandial hyperlipidemia (PHL) and the level of hormones which regulate metabolism, lipids in particular, in patients with ischemic heart disease (IHD) vs those in healthy persons and patients with thyrotoxicosis as well as to clarify whether IHD pathogenesis correlates with fat metabolism disturbance. Lipid and apoprotein parameters of dyslipoproteinemia, concentrations of insulin, hydrocortisone, T3, T4 and thyrotropic hormone were tested before and 3, 6 hours after fat loading in IHD patients with angiographically documented coronary atherosclerosis, in healthy persons and patients with diffuse toxic goiter. In IHD patients postprandial PHL differed from that in healthy persons and thyrotoxicosis patients by higher and growing up to hour 6 after fat loading hypertriglyceridemia associated with lowering of antiatherogenic cholesterol of HDLP. In thyrotoxicosis both fasting and afterload lipid and apoprotein indices of the lipoprotein spectrum continued at low level except triglycerides the level of which returned to normal level. The hormonal spectrum in IHD patients was characterized by higher fasting insulin and its noticeable rise after fat loading. As healthy persons and patients with thyrotoxicosis had no significant changes in hormones levels after fat loading, it is suggested that development of atherogenic postprandial PHL caused primarily by hormone dysregulation of fat metabolism with a leading role of hyperinsulinemia contributes much to pathogenesis of IHD.
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PMID:[Hormonal dysregulation of lipid metabolism in pathogenesis of ischemic heart disease]. 1502 92

We have previously shown that atherosclerotic apolipoprotein E-deficient (apoE(-/-)) x LDL receptor-deficient (LDLR(-/-)) mice develop myocardial infarction when exposed to hypoxic stress. This study was performed to assess the role of thrombin and thrombosis in this process. ApoE(-/-) x LDLR(-/-) mice were fed a cholesterol-rich diet for 8 mo and were then subjected to hypoxic stress while receiving isoflurane anesthesia. One group received a bolus dose (5.6 micromol/kg) of the thrombin inhibitor melagatran, and control animals received PBS 10 min before the hypoxic stress. The mice were exposed to 10 min of hypoxia followed by normoxia. Ten minutes after the stress, Alzet pumps delivering melagatran (20 nmol x kg x (-1)min(-1)) or PBS were implanted, and the mice were allowed to recover for 48 h. The cardiac response was analyzed by histology, immunohistochemistry, and serum troponin T assay. All animals showed reversible ECG changes as a sign of ischemia during hypoxic stress, and 50% developed infarctions afterward as judged by troponin T levels. The group that received thrombin inhibitor had significantly lower troponin T and smaller myocardial infarctions than the PBS-treated group. These data show that thrombin generation is an important pathogenetic factor and suggest that coronary thrombosis is involved in myocardial infarction in atherosclerotic mice. Exposure of atherosclerotic mice to hypoxia leads to myocardial infarction through a two-phase pathway in which acute transient ischemia is followed by thrombin-dependent, irreversible, myocardial ischemia and myocardial cell death.
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PMID:Thrombin inhibitor reduces myocardial infarction in apoE-/- x LDLR-/- mice. 1503 Nov 24

Individuals with a heterozygous mutation at the ataxia-telangiectasia mutated gene (ATM) have been reported to be predisposed to ischemic heart disease. This report examined for the first time the effect of a heterozygous ATM mutation (ATM(+)(/-)) on plasma lipid levels and atherosclerosis intensity using ATM(+/-), ATM(+)(/+) (wild type), ATM(+)(/+)/LDLR(-)(/-) (low density lipoprotein receptor knockout), ATM(+)(/-)/LDLR(-)(/-), ATM(+)(/+)/ApoE(-)(/-) (apolipoprotein E knockout), and ATM(+)(/-)/ApoE(-)(/-) mice. Our data demonstrated that the plasma cholesterol and triglyceride levels in ATM(+)(/-) and ATM(+)(/-)/LDLR(-)(/-) mice were approximately the same as those in ATM(+)(/+) and ATM(+)(/+)/LDLR(-)(/-) control mice, respectively. In contrast, the plasma cholesterol level was significantly higher in ATM(+)(/-)/ApoE(-)(/-) mice than in ATM(+)(/+)/ApoE(-)(/-) control mice. In addition, the ATM(+)(/-)/ApoE(-)(/-) mice showed higher plasma apoB-48 levels, slower clearance for plasma apoB-48-carrying lipoproteins, and more advanced atherosclerotic lesions in the aorta compared with the ATM(+)(/+)/ApoE(-)(/-) mice. These novel results suggest that the product of ATM is involved in an apoE-independent pathway for catabolism of apoB-48-carrying remnants; therefore, superimposition of a heterozygous ATM mutation onto an ApoE deficiency background reduces the clearance of apoB-48-carrying lipoproteins from the blood circulation and promotes the formation of atherosclerosis.
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PMID:Heterozygous mutation of ataxia-telangiectasia mutated gene aggravates hypercholesterolemia in apoE-deficient mice. 1586 39

We studied parameters of structural and oxidative modification of low density lipoproteins (LDL) in 80 men aged 35 - 65 years with coronary atherosclerosis verified at coronary angiography in comparison with 80 men of the same age without ischemic heart disease. Biochemical studies included determination of parameters of lipid blood composition by enzymatic methods, subfractional LDL profile by electrophoresis in 2 - 16% gradient polyacrylamide gel, degree of oxidative modification of lipid (lipid peroxidation products) and apoprotein (carbonyl groups) components of LDL by fluorometric and spectrophotometric methods. In men with coronary atherosclerosis we revealed elevated level of small dense LDL and substantially oxidized lipid and apoprotein components of these particles. Independent association of structural and oxidative modification was shown.
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PMID:[Atherogenic oxidative and structural modification of low density lipoproteins in men with coronary atherosclerosis]. 1826 Sep 58


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