Atherosclerosis is caused by a series of pathologic changes at the cellular level, with formation of macrophage-derived foam cells occurring at an early stage. Most of the cholesteryl esters in macrophage foam cells are produced by the enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT). Two ACAT genes, Acat1 and Acat2, exist in ...

In macrophages, the accumulation of cholesteryl esters synthesized by the activated acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1) results in the foam cell formation, a hallmark of early atherosclerotic lesions. In this study, with the treatment of a glucocorticoid hormone dexamethasone (Dex), lipid staining results clearly showed the large ...

BackgroundOne of the most important factors in the initiation and progression of atherosclerosis is the default in macrophage cholesterol homeostasis. Many genes and transcription factors such as Peroxisome Proliferators Activated Receptors (PPARs) and Acyl Coenzyme A: Cholesterol Acyltransferase1 (ACAT1) are involved in cholesterol ...

We have previously reported that human ACAT1 gene produces a chimeric mRNA through an interchromosomal processing of two discontinuous RNAs transcribed from chromosomes 1 and 7. The chimeric mRNA uses AUG_1397�1399 and GGC_1274�1276 respectively as translation initiation codons to produce ...

We have previously reported that human ACAT1 mRNAs produce the 50 kDa protein using the AUG(11397-1399) initiation codon, and also a minor 56 kDa isoform using the upstream in-frame GGC(1274-1276) initiation codon. The GGC(1274-1276) codon is located at the optional long 5'-untranslated region (5'-UTR, nt 1-1396) of the mRNAs. The DNA sequences ...

High levels of the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) are present in atherosclerotic lesions. TNF-alpha regulates expression of multiple genes involved in various stages of atherosclerosis, and it exhibits proatherosclerotic and antiatherosclerotic properties. ACAT catalyzes the formation of cholesteryl esters (CE) in ...

High levels of the inflammatory cytokine tumor necrosis factor-? (TNF-?) are present in atherosclerotic lesions. TNF-? regulates expression of multiple genes involved in various stages of atherosclerosis, and it exhibits proatherosclerotic and antiatherosclerotic properties. ACAT catalyzes the formation of cholesteryl esters (CE) in monocytes/macrophages, ...

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear receptor activated by fatty acid derivatives and hypolipidemic drugs of the fibrate class. PPARalpha is expressed in monocytes, macrophages, and foam cells, suggesting a role for this receptor in macrophage lipid homeostasis with consequences for atherosclerosis development. Recently, it was shown that ...

Metabolism This collection curated by Stephen Chanock (sc83a@nih.gov) Gene Description Sequences Sequence assembly Predicted SNPs having score >= 0.99 ACAT1 Acetyl-Coenzyme A acetyltransferase 1 (acetoacetyl Coenzyme A thiolase) D90228 D10511 ACAT2 Acetyl-Coenzyme

In contrast to some published studies of murine macrophages, we previously showed that ACAT inhibitors appeared to be anti-atherogenic in primary human macrophages in that they decreased foam cell formation without inducing cytotoxicity. Herein, we examined foam cell formation and cytotoxicity in murine ACAT1 knockout (KO) macrophages in an attempt to ...

Significant increases in levels of cholesterol and cholesterol oxidation products are detected in the hippocampus undergoing degeneration after excitotoxicity induced by the potent glutamate analog, kainate (KA), but until now, it is unclear whether the cholesterol is in the free or esterified form. The present study was carried out to examine the expression of the enzyme ...

Acyl-CoA:cholesterol acyltransferase (ACAT) is a membrane-bound enzyme that produces cholesteryl esters intracellularly. Two ACAT genes (ACAT1 and ACAT2) have been identified. The expression of ACAT1 is ubiquitous, whereas that of ACAT2 is tissue restricted. Previous research indicates that ACAT1 may contain seven ...

The catecholic xanthones and flavonoids 1-13 were isolated from the root bark of Cudrania tricuspidata. Compounds 1 and 3-8 exhibited significant antioxidant activity against low-density lipoprotein (LDL) oxidation in the thiobarbituric acid-reactive substance (TBARS) assay. Among them, prenylated flavonoids 10-12 showed an inhibitory effect on the NO production and iNOS ...

Cholesterol metabolism has been implicated in the pathogenesis of several neurodegenerative diseases, including the abnormal accumulation of amyloid-?, one of the pathological hallmarks of Alzheimer disease (AD). Acyl-CoA:cholesterol acyltransferases (ACAT1 and ACAT2) are two enzymes that convert free cholesterol to cholesteryl esters. ACAT inhibitors have ...

Twenty years after Chernobyl accident, the daily ingestion of foodstuff grown on contaminated grounds remains the main source for internal exposure to ionizing radiations, and primarily to cesium 137 ((137)Cs). Though the effects of a long-term internal contamination with radionuclides are poorly documented, several non-cancerous pathologies have been described in this population. However, lipid ...