Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the influence of the apolipoprotein E polymorphism on the occurrence of coronary artery disease (CAD) and on serum lipids, lipoproteins and apolipoproteins we studied 145 patients with angiographically defined CAD and compared them with 153 control subjects without history or complaints of vascular disease and with 35 subjects without significant stenosis on coronary arteriography. Subjects with hypertension, diabetes mellitus and endocrine or metabolic disorders were excluded. Covariance analysis and logistic regression analysis were performed with adjustment for age, sex, smoking habits and relative body weight. There were no significant differences for the apoE phenotypes on risk of cardiovascular disease. The CAD group had significantly higher mean values of serum cholesterol and triglycerides, very-low-density lipoprotein (VLDL)-cholesterol and VLDL-triglycerides, low-density lipoprotein (LDL)-cholesterol and apoprotein B; they had lower high-density lipoprotein (HDL)-cholesterol and apo A-I. The combination of LDL-cholesterol, apoA-I and VLDL-cholesterol was the best model in predicting cardiovascular disease. ApoE phenotype group E3/E2 had significantly lower values for serum cholesterol, LDL-cholesterol, and apoB and higher levels of apoE in comparison with the phenotype groups E3/E3 and E4/E3. The combination of LDL-cholesterol, cholesterol, apoE and VLDL-triglycerides was the best model in predicting the apoE phenotype. Thus, taking other risk factors into account, the apoE phenotype is not an independent risk factor for CAD; the apoE polymorphism influences lipoprotein levels and possibly, in that way, indirectly also the risk for CAD.
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PMID:Apolipoprotein E phenotypes, serum lipoproteins and apolipoproteins in angiographically assessed coronary heart disease. 194 27

Endothelial cells, because of their proximity to the blood stream, provide an attractive system for gene transfer and delivery of gene products that control foci of vascular disease processes. We describe a simple, new methodology to achieve highly efficient transformation of cultured human endothelial cells derived from umbilical veins (HUVEC). A plasmid pCH110 containing coding region for beta-galactosidase driven by SV 40 early promoter region was employed to transfect HUVEC. The developed protocol exploits the role of apolipoprotein E (Apo E) in the metabolism of Apo E-containing lipoproteins and its high affinity binding to LDL receptors. DNA transfection of cultured HUVEC was carried out using standard transfection methods including calcium phosphate precipitation, polybrene mediated transfection, and lipofection. The new methodology of transfecting HUVEC employed Apo E adsorbed lipofection reagent-DNA complex, and was found to be the most efficient procedure to transform HUVEC in comparison to the standard methods used in this study.
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PMID:High-efficiency transformation of human endothelial cells by Apo E-mediated transfection with plasmid DNA. 766 41

Alzheimer's disease (AD) is rapidly moving from the obscure category of degenerative diseases to the more precise one of metabolic disorders. Recent discoveries have substantiated the hypothesis that AD results from the deposition of beta-amyloid, which is formed by polymers of a proteolytic fragment of the amyloid protein precursor (APP), and may induce intraneuronal aggregation of the microtubule-associated protein tau into paired helical filaments and neuronal death. There is also evidence that AD is a heterogeneous age-related disorder of multifactorial origin, which may arise as a consequence of point mutations of genes encoding APP or other proteins involved in its metabolism (familial AD), or a combination of genetic and non-genetic factors (sporadic AD). Familial AD displays genetic and phenotypic heterogeneity, meaning that mutations of different genes may cause the AD phenotype, and that different mutations of the same gene may cause phenotypically distinct disorders, including Alzheimer-type dementia and cerebral amyloid angiopathy with cerebral hemorrhages and stroke. On the other hand, aging, gender, head trauma, and variants of the apolipoprotein E gene have been shown to increase the risk of developing the more prevalent sporadic form of AD. The mechanisms by which these factors influence amyloidogenesis are beginning to be understood, and this will provide a rational basis for future therapy. Knowledge of the molecular basis of AD would eventually allow accurate risk prediction before the disease becomes clinically apparent, and better chances for early treatment and prevention.
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PMID:Alzheimer's disease, beta-amyloidosis, and aging. 769 97

Advances in the study of cerebrovascular disease suggest that many risk factors for stroke are under genetic influence. Epidemiologic studies show that parental and sibling histories of cerebral ischemic events are associated with an increased risk of stroke. Explanations for familial stroke aggregation include differential phenotypic expression of apolipoprotein (a) and apolipoprotein E, racial variations in the distribution of vascular disease, identification of the autosomal-dominant disorder cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, specific point mutations in the mitochondrial-related disorders, and identification of the clinical significance of hereditable coagulopathies. Greater understanding of these factors may lead to early recognition of and intervention in stroke.
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PMID:Genetics of ischemic stroke. 774 12

We have investigated the effect of genotypes of apolipoprotein E (ApoE) on the pathologies found in Alzheimer's disease (AD) and its related gene expression in 38 aged human brains obtained from consecutive autopsied cases. ApoE2/3, -3/3, -3/4, and -4/4 were typed in those aged brains, with ApoE3/3 being most prevalent. The AD pathologies were undetectable in ApoE2/3 brains, but were frequently observed in the other ApoE groups. In ApoE3/3 brains, 55%, 34%, and 24% of the cortical sections examined showed senile plaques (SPs), neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA), respectively. In ApoE4/4 brains, the SP formation was significantly higher. The ApoE genotype neither affected ApoE, APP, or tau mRNA level, nor the differential expression of the latter two. These results suggest that ApoE4/4 accelerates and ApoE2/3 decelerates the development of the AD pathologies in the aged brain, but this is not through alterations of the APP and tau gene expression.
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PMID:Apolipoprotein E genotype, Alzheimer's pathologies and related gene expression in the aged population. 777 5

To determine whether apolipoprotein E (APOE) genotype affects neuropathology in Lewy body disease (LBD), we examined 18 cases of LBD that did not have concurrent Alzheimer's disease by the CERAD criteria. We obtained APOE genotypes, determined diffuse beta-amyloid plaque (A beta P) and Lewy body densities in multiple brain regions, and graded the intensity of CA2-3 ubiquitin-positive neurites, vacuolar change, nigral pathology, amyloid angiopathy, and subpial amyloid deposition. The APOE allele frequencies were as follows: epsilon 2, 0.14 +/- 0.07; epsilon 3, 0.64 +/- 0.08; and epsilon 4, 0.22 +/- 0.03. The mean A beta P density was lower in APOE epsilon 3/3 cases (14.5 A beta Ps per mm2) than in the groups with the APOE epsilon 2 (67.0) or APOE epsilon 4 (46.6) alleles. This difference was due largely to the difference between A beta P density in the APOE epsilon 2 group and the APOE epsilon 3/3 group (F = 5.525, p < 0.02). CA2-3 neuritic degeneration was greater in those with the APOE epsilon 4 allele than in those with the APOE epsilon 3/3 genotype (grade = 1.9 +/- 1.3 versus 0.938 +/- 0.9; Kruskal-Wallis test statistic = 6.962, p < 0.05). These data are consistent with the hypothesis that APOE genotype may affect neuropathology in LBD.
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PMID:Apolipoprotein E genotype and Lewy body disease. 782 44

The localization of apolipoprotein E (ApoE) has been examined immunohistochemically in the autopsied brains of middle-aged and old-aged control subjects, with and without amyloid beta protein (A beta) deposits, and of Alzheimer's disease patients. Senile plaques were consistently labeled with ApoE antiserum even in the very early stage of senile plaque formation seen in the fifth decade. In the cerebellar molecular layer, small dots of ApoE immunoreactivity, which were prominent in the Alzheimer's disease subjects, were observed in addition to immunoreactivity in diffuse plaques. ApoE antisera labeled all of the extracellular neurofibrillary tangles (NFT), whereas only a small minority of extracellular NFT were positive for A beta. A punctate pattern of ApoE immunoreactivity was seen at the media of the meningeal vessels lacking amyloid, when senile plaques were present in the nearby cortex. In the early stage of amyloid angiopathy, the distribution of ApoE immunoreactivity was much more extensive than that of A beta positivity. These findings suggest that ApoE accumulates in the early stage of senile plaque formation and, furthermore, that ApoE accumulation precedes A beta deposition in extracellular NFT and amyloid angiopathy.
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PMID:Presence of apolipoprotein E on extracellular neurofibrillary tangles and on meningeal blood vessels precedes the Alzheimer beta-amyloid deposition. 784 69

To study the pathogenesis of cerebral amyloid angiopathy (CAA), organ cultures of canine leptomeninges were incubated with fluorescein-conjugated amyloid beta-protein (FA beta, residues 1-40; 10 nM to 200 microM). Fluorescence microscopy showed focal and dose-dependent FA beta binding to blood vessels affected by CAA at FA beta-concentrations as low as 10 nM. The new A beta deposits appeared to be extracellular and were localized to the middle and outer layers of leptomeningeal arterioles. FA beta partially co-localized with apolipoprotein E (ApoE) as revealed by confocal microscopy, suggesting that A beta in situ binds to ApoE. Young dogs or old dogs without CAA showed no deposition of FA beta. Our results indicate that after initiation of CAA pathology, physiological concentrations of soluble A beta are sufficient to sustain its further deposition and therefore the progression of CAA.
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PMID:Experimental deposition of Alzheimer amyloid beta-protein in canine leptomeningeal vessels. 854 73

In the brains of ine cases with cerebrovascular disease, one with mixed dementia, one with amyloid angiopathy and two non-neurological controls, we found three cases with focal accumulation of apolipoprotein E (apo-E) in dystrophic axons and accompanying macrophages. Since amyloid precursor protein (APP) and chromogranin A (CgA) accumulate after axonal damages, and are sensitive markers of the white matter lesions, the regional distribution of apo-E was compared to that of APP and CgA. apo-E-immunoreactive axons were present in the periphery of an infarction with neighboring macrophages, but not in mild white matter lesions that contained APP- or CgA-immunoreactive fiber bundles. The results suggest a role of apo-E in recycling cholesterol and other membrane components via macrophages into remodeling neurites in the brain, but this phenomenon is restricted to the periphery of infarction and may be less prominent than in the peripheral nervous system.
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PMID:Immunohistochemical study of apolipoprotein E in human cerebrovascular white matter lesions. 861 81

The presence of apolipoprotein E (ApoE)-E4 allele has been implicated as a risk factor for Alzheimer's disease (AD). We examined the occurrence of ApoE 4 alleles in AD associated with cerebral amyloid angiopathy and other vascular lesions. We found significantly high frequency of the ApoE 4 allele in AD with moderate to severe CAA. The frequency of the allele was also high in AD cases with other vascular lesions such as multiple infarcts and lacunes. As previously reported, we confirm a greater frequency of the ApoE 4 allele in the diffuse Lewy body variant of AD. Our results suggest ApoE 4 allele to be a significant factor in the development of CAA in AD. While this may be related to increased brain amyloid load as a consequence of ApoE genotype, the possibility exists that ApoE may be a specific factor in vascular abnormalities associated with AD.
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PMID:Apolipoprotein E alleles and brain vascular pathology in Alzheimer's disease. 862 96


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