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)

1. The relationship between atherosclerosis development and changes in arterial fatty acid binding protein (FABP) activity was investigated in the aortas of New Zealand rabbits which were fed an atherogenic diet containing 1% cholesterol and 3% peanut oil for 16 weeks. 2. At 4-week intervals, FABP activity, cholesterol and microsomal acylCoA:cholesterol acyltransferase (ACAT) activity were determined in aortic tissue and serum cholesterol was measured; age-matched normal rabbits served as control comparators. 3. Serum cholesterol increased from 35 mg/dl in the normal rabbits to 2290 mg/dl in the 16-week cholesterol-fed rabbits. 4. The microsomal fraction isolated from cholesterol-fed rabbit aortas exhibited a progressive elevation in ACAT activity as time on the diet increased. By 12-16 weeks, ACAT activity had increased approximately 10-fold relative to normal activity. 5. Arterial cholesterol content of the cholesterol-fed animals increased from less than 2 mg/g wet weight to greater than 10 mg/g wet weight at 12 and 16 weeks. In contrast, arterial FABP activity gradually decreased with time on the cholesterol diet; a significant decrease (P less than 0.05) was observed at 16 weeks, where palmitoyl CoA binding was decreased from 61.0 to 36.3 pmol/mg protein. 6. In the cholesterol-fed rabbits, total arterial cholesterol and ACAT activity showed a significant (P less than 0.05) inverse correlation to FABP activity with correlation coefficients of -0.93 and -0.95, respectively. 7. Additionally, FABP activity increased significantly (P less than 0.05) in the 16-week normal rabbit as compared to the 4-week normal rabbit, suggesting an age-dependent interaction.
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PMID:Temporal evaluation of fatty acid-binding protein (FABP) activity in association with the development of atherosclerosis in the rabbit. 135 84

We conducted a community-based case-control study of African-American men and women in the Atherosclerosis Risk in Communities Study. The allele frequencies of the Gly972Arg variant of the insulin receptor substrate-1 (IRS-1) gene and the Ala54Thr variant of the fatty acid binding protein 2 (FABP2) gene were compared in 992 normal control subjects and three patient groups: 1) 321 type 2 diabetic individuals, 2) 260 severely obese individuals, and 3) 258 markedly hyperinsulinemic individuals without diabetes. Allele frequencies of Gly972Arg IRS-1 and Ala54Thr FABP2 were 0.07 and 0.22, respectively; there were no differences in allele or genotype frequencies between patients and control subjects for either gene variant. In weighted linear regression of all patients and control subjects, the presence of the IRS-1 gene variant was associated with a 0.85 (0.42) kg/m2 higher BMI (P = 0.04). In addition, individuals with at least one IRS-1 Arg972 allele and two FABP2 Thr54 alleles had a BMI of 33.3 (7.9) kg/m2, compared with 30.0 (6.3) kg/m2 for those with neither allele (P = 0.05). These results suggest that in African-Americans, these variants in the IRS-1 and FABP2 genes are not associated with the risk of type 2 diabetes, severe obesity, or marked hyperinsulinemia, but that their independent and joint effects may be associated with small increases in BMI.
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PMID:Variants of the insulin receptor substrate-1 and fatty acid binding protein 2 genes and the risk of type 2 diabetes, obesity, and hyperinsulinemia in African-Americans: the Atherosclerosis Risk in Communities Study. 1048 Jun 21

We investigated the potential role of the genetic variation at the intestinal fatty acid binding protein gene (FABP2) in influencing lipid levels in a representative sample of the Framingham Offspring Study participants (n=1930). In men, the T54 allele was associated with significantly higher LDL-cholesterol (3.47+/-0.83 vs. 3.36+/-0.83 mmol/l; P<0.047), and ApoB (1.04+/-0.23 vs. 1.01+/-0.24 g/l; P<0.020) after adjustment for familial relationship, age, BMI, smoking, alcohol intake and the use of beta-blockers compared with the A54 allele. This relationship with ApoB continued to be significant after adjustment for APOE genotype (P<0.034). In women, the T54 allele was associated with significantly higher total-cholesterol (5.32+/-1.01 vs. 5.17+/-0.98 mmol/l; P<0.049) and LDL-cholesterol (3.31+/-0.93 vs. 3.18+/-0.85 mmol/l; P<0.023) after adjustment for covariates and menopausal status, estrogen therapy and APOE genotype. In men, the T54 allele was associated with significantly higher levels of small VLDL and lower levels of large HDL. Moreover, there was no significant relationship between FABP2 alleles and lipoprotein diameter or the prevalence of coronary heart disease in both genders. Our data are consistent with the T54 IFABP increasing the flux of lipids through the enterocyte leading to an increase in chylomicron secretion.
Atherosclerosis 2001 Dec
PMID:Association of the A/T54 polymorphism in the intestinal fatty acid binding protein with variations in plasma lipids in the Framingham Offspring Study. 1173 Aug 22

The metabolic syndrome is a cluster of metabolic and inflammatory abnormalities including obesity, insulin resistance, type 2 diabetes, hypertension, dyslipidemia, and atherosclerosis. The fatty acid binding proteins aP2 (fatty acid binding protein [FABP]-4) and mal1 (FABP5) are closely related and both are expressed in adipocytes. Previous studies in aP2-deficient mice have indicated a significant role for aP2 in obesity-related insulin resistance, type 2 diabetes, and atherosclerosis. However, the biological functions of mal1 are not known. Here, we report the generation of mice with targeted null mutations in the mal1 gene as well as transgenic mice overexpressing mal1 from the aP2 promoter/enhancer to address the role of this FABP in metabolic regulation in the presence or absence of obesity. To address the role of the second adipocyte FABP in metabolic regulation in the presence and deficiency of obesity, absence of mal1 resulted in increased systemic insulin sensitivity in two models of obesity and insulin resistance. Adipocytes isolated from mal1-deficient mice also exhibited enhanced insulin-stimulated glucose transport capacity. In contrast, mice expressing high levels of mal1 in adipose tissue display reduced systemic insulin sensitivity. Hence, our results demonstrate that mal1 modulates adipose tissue function and contributes to systemic glucose metabolism and constitutes a potential therapeutic target in insulin resistance.
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PMID:Role of the fatty acid binding protein mal1 in obesity and insulin resistance. 1254 Jun

Although postprandial hypertriglyceridemia is a major contributing factor in the development of atherosclerosis, little information is available on the effect of insulin resistance and diabetes on intestinal fat transport. The aim of the present study was to examine intracellular events that govern lipid transport and apolipoprotein (apo) B-48-containing lipoprotein assembly in the small intestine of Psammomys obesus, a model of nutritionally induced insulin resistance and type 2 diabetes. Animals with normoglycemia/hyperinsulinemia and hyperglycemia/hyperinsulinemia exhibited high levels of triglycerides (TGs) in the plasma and intestine and postprandial plasma chylomicrons and apo B-48 compared with normoglycemic/normoinsulinemic animals. In vitro studies, using cultured jejunal explants incubated with either [14C]oleic acid or [35S]methionine, revealed their higher efficiency in de novo TG synthesis, apo B-48 biogenesis, and TG-rich lipoprotein assembly. Accordingly, enhanced monoacylglycerol and diacylglycerol acyltransferase activity was also discernible and concomitant with an increased content of L-fatty acid binding protein and in vivo chylomicron production rates. However, both the I-fatty acid binding protein amount and the apo B-48 proteasomal degradative pathway were decreased. Overall, our findings show that the development of an insulin-resistant/diabetic state in Psammomys obesus triggers the whole intra-enterocyte machinery, leading to lipoprotein assembly and favoring the intestinal oversecretion of apo B-48-lipoproteins, which may contribute to characteristic hypertriglyceridemia.
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PMID:Cellular aspects of intestinal lipoprotein assembly in Psammomys obesus: a model of insulin resistance and type 2 diabetes. 1451 38

The effect of infection with Chlamydia pneumoniae on host messenger RNA expression in human monocytic cells with complement DNA microarrays was studied. The data chronicle a cascade of transcriptional events affecting 128 genes, many of which have not previously been reported to be affected by C. pneumoniae infection. Down-regulated genes are primarily associated with RNA and DNA metabolism, chromosomal stability, and cell-cycle regulation. Up-regulated messages include those for a variety of genes with important proinflammatory functions. Many of the up-regulated genes-including the hyaluron receptor CD44, vasoconstrictor endothelin-1, smooth muscle growth factor heparin-binding EGF-like growth factor, and fatty acid binding protein-4-had been previously described as linked to the development of atherosclerosis and other chronic inflammatory diseases. C. pneumoniae-infected monocytes can contribute to the development and progression of diseases for which acute or chronic inflammation has been shown to be important, such as atherosclerosis.
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PMID:Infection of U937 monocytic cells with Chlamydia pneumoniae induces extensive changes in host cell gene expression. 1459 87

Obesity is a common and serious metabolic disorder in the developed world that is occasionally accompanied by type II diabetes, atherosclerosis, hypertension, and hyperlipidemia. We have found that mesoderm-specific transcript (Mest)/paternally expressed gene 1 (Peg1) gene expression was markedly enhanced in white adipose tissue of mice with diet-induced and genetically caused obesity/diabetes but not with streptozotocin-induced diabetes, which does not cause obesity. Administration of pioglitazone, a drug for type II diabetes and activator of peroxisome proliferator-activated receptor (PPAR)gamma, in obese db/db mice reduced the enhanced expression of Mest mRNA in adipose tissue, concomitant with an increase in body weight and a decrease in the size of adipose cells. Ectopic expression of Mest in 3T3-L1 cells caused increased gene expression of adipose markers such as PPARgamma, CCAAT/enhancer binding protein (C/EBP)alpha, and adipocyte fatty acid binding protein (aP)2. In transgenic mice overexpressing Mest in adipose tissue, enhanced expression of the adipose genes was observed. Moreover, adipocytes were markedly enlarged in the transgenic mice. Thus Mest appears to enlarge adipocytes and could be a novel marker of the size of adipocytes.
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PMID:Mest/Peg1 imprinted gene enlarges adipocytes and is a marker of adipocyte size. 1535 8

Rapamycin (Sirolimus) is a potent immunosuppressive drug that reduces renal transplant rejection. Hyperlipidemia is a significant side effect of rapamycin treatment, and frequently leads to cardiovascular disease. Adipocyte fatty acid binding protein (aP2) is a member of the cytoplasmic fatty acid binding protein (FABP) family. aP2 has been shown to affect insulin sensitivity, lipid metabolism, lipolysis, and has recently been shown to play an important role in atherosclerosis. We found that aP2 messenger RNA (mRNA) was increased in human THP-1 cells after rapamycin treatment. Exposure of human differentiated THP-1 cells to rapamycin led to a time- and dose-dependent induction of aP2 mRNA expression. While aP2 expression was undetectable in undifferentiated THP-1 cells, aP2 was induced in these cells by rapamycin. These data suggest that rapamycin-induced aP2 may play a role in increased triglyceride accumulation.
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PMID:Sirolimus upregulates aP2 expression in human monocytes and macrophages. 1568 34

The aim of our study was to investigate the combination of Chlamydophila pneumoniae and human cytomegalovirus (HCMV) as a pathogenic factor in atherosclerosis. Accordingly, we tested by means of PCR and immunohistochemistry the presence of these pathogens in the same atherosclerotic carotid specimen. The histology of the samples and the patients' antibodies against these pathogens were evaluated. Further, we examined the impact of C. pneumoniae and HCMV infection on the gene expression of the human monocytic cell line U937. Six of the 22 samples contained only C. pneumoniae, 4 contained only HCMV, 7 contained both C. pneumoniae DNA and/or antigens of both pathogens, and 5 samples were negative. No correlation was found between the presence of these microbes and either the cellular structure of the plaques, or the serostatus of the patients. The infection of U937 cells with HCMV and especially C. pneumoniae induced inflammation and atherosclerosis-related genes. Furthermore, the doubly-infected cells produced higher levels of the mRNA of pro-platelet basic protein and fatty acid binding protein 4. In conclusion, C. pneumoniae is often present in combination with HCMV in atherosclerotic carotid lesions. The in vitro coinfection model reveals that the doubly-infected monocytes are potent expressors of proatherosclerotic genes, suggesting that this coinfected population may accelerate the process of atherosclerosis.
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PMID:Chlamydophila pneumoniae and human cytomegalovirus in atherosclerotic carotid plaques--combined presence and possible interactions. 1669 49

Type 2 diabetes, a major risk factor for atherosclerosis, is associated with a cluster of lipid risk factors, many of which can be mechanistically linked with underlying dysregulated fatty acid metabolism and elevated plasma non-esterified fatty acids (NEFA). Thus, we tested the hypothesis that elevated NEFA dysregulates lipid metabolism at the levels of lipid synthesis and gene expression in THP-1 monocyte derived macrophages (MDM). THP-1 MDM incubated with oleic acid (OA) and a BODIPY-conjugated NEFA, accumulate, respectively, intracellular inclusions that are positive for oil red O and BODIPY-labeling. Parallel studies with [(14)C]OA show dose-dependent accumulation of intracellular (14)C-labeled neutral lipid, almost exclusively as triglyceride; the rate of [(3)H]OA uptake increases as THP-1 MDM convert to foam cells. Preincubation of THP-1 MDM with higher concentrations of OA (1.8mM versus 0.2mM) was associated with enhanced uptake of Ac-LDL, and increased expression of adipocyte fatty acid binding protein, FAT/CD36, and cyclooxygenase-2 (COX-2); COX-2 mass and activity also increased. These observations suggest a mechanistic link between sustained elevations in albumin-bound NEFA and foam cell formation that may be mediated by enhanced adipogenesis, increased uptake of modified LDL, and upregulated formation of eicosanoids, which may be proinflammatory.
Atherosclerosis 2007 May
PMID:Sustained elevations in NEFA induce cyclooxygenase-2 activity and potentiate THP-1 macrophage foam cell formation. 1687 Jan 93


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