Biomedical subjects

Y Asami

Publications and source records attributed to Y Asami.

At least 19 recordsLinked to original sources

PubMed2004

Immuno-histochemical expression of alpha1, alpha2 and alpha3 integrin subunits during angiogenesis in vitro.

Aortic explants were obtained from mouse fetuses and cultured in collagen gels. Immuno-fluorescence microscopy, antibodies (anti alpha1, alpha2 and alpha3 integrin subunits) were used. Fibroblastic cells migrated from the aortic explant after one day of cultivation. The migrating cells located in the peripheral part of the aortic explant were positive for alpha1 and alpha2 integrin subunit antibodies. Immuno-fluorescence-positive staining for the alpha3 integrin subunit antibody was clearly seen in the migrating cells located near the aortic explant and surrounding tube-like structures. In an immuno-electron microscope study performed by pre-embedding immuno labeling, gold particles associated with the alpha3 integrin subunit were found to reside on the membranes of the cells surrounding the capillary-like tubes. Two synthetic peptides, GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro) and KDGEA (Lys-Asp-Gly-Glu-Ala), were added to the growth medium to study their effects on cell migration. KDGEA, a compound containing the recognition sequence for alpha2beta1 integrin, decreased cell migration, while GRGDSP exhibited no effect. The migration of fibroblastic cells is an important phenomenon for tube formation. The present study suggested that the alpha1 and alpha2 integrin subunits are both involved in the cell migration, and more specifically, that the alpha2 integrin subunit participates in cell migration through the KDGEA sequence. The alpha3 integrin subunit played a role in tube formation.

Animals↗

PubMed2001

Production of recombinant human bile salt-stimulated lipase in Pichia pastoris.

Recombinant human bile salt-stimulated lipase (rhBSSL) was efficiently expressed under the control of the AOX1 gene promoter in Pichia pastoris. Human BSSL has 16 successively repeated sequences in the carboxy terminal region. The sequence consists of 11 amino acid residues. The coding sequence for the middle 11 of the 16 repeats was removed from hBSSL cDNA to facilitate efficient secretory expression. The clone used for fermentation was a transformant of GS115 (his4) integrated with four copies of the expression cassette containing the modified hBSSL cDNA. Unique fermentation conditions were required for efficient expressions of rhBSSL in the high cell-density fermentation. A sufficient glycerol feed at 30 degrees C and pH 4 under an adequate concentration of dissolved oxygen in the growth phase make the cells active over a long induction period of approximately 15 days. On methanol induction, the concentration of dissolved oxygen should be maintained very low in the presence of sorbitol and skimmed milk at 20 degrees C and pH 5.7. Under these conditions, 0.8-1 g of rhBSSL was secreted in 1 liter of the medium. By immunoelectron microscopy, rhBSSL-tagged gold particles were located in secretion microbodies after the beginning of methanol induction. The secreted rhBSSL was efficiently captured and purified by expanded bed adsorption chromatography.

Cloning, Molecular↗

PubMed2001

Role of DNA ligase in the illegitimate recombination that generates lambdabio-transducing phages in Escherichia coli.

We studied the role of DNA ligase in illegitimate recombination in Escherichia coli. A temperature-sensitive mutation in the lig gene reduced the frequency with which lambdabio-transducing phages were generated to 10-14% of that of wild type under UV irradiation. Reintroduction of the lig gene into this mutant restored the frequency of recombinant phage generation to that of wild type. Furthermore, overexpression of DNA ligase enhanced illegitimate recombination by 10-fold with or without UV irradiation. In addition, when DNA ligase was present in only limited amounts, UV-induced or spontaneous illegitimate recombination occurred exclusively at hotspot sites that have relatively long sequences of homology (9 or 13 bp). However, when DNA ligase was overexpressed, most of the illegitimate recombination took place at non-hotspot sites having only short sequences of homology (<4 bp). Thus, the level of ligase activity affects the frequency of illegitimate recombination, the length of sequence homology at the recombination sites, and the preference for recombination at hotspots, at least after UV irradiation. These observations support our hypothesis that the illegitimate recombination that generates lambdabio-transducing phages is mediated by the DNA break-and-join mechanism.

Base Sequence↗

PubMed2000

Value of acceleration flow and the prestenotic to stenotic coronary flow velocity ratio by transthoracic color Doppler echocardiography in noninvasive diagnosis of restenosis after percutaneous transluminal coronary angioplasty.

OBJECTIVES: The study evaluated the value of coronary flow velocity measurement by transthoracic color Doppler echocardiography (TTCDE) for the noninvasive diagnosis of restenosis after percutaneous transluminal coronary angioplasty (PTCA) for left anterior descending coronary artery (LAD) lesions. BACKGROUND: Recent advances in TTCDE provide coronary flow velocity measurements in the LAD under the guidance of color flow mapping. METHODS: We studied 53 patients who underwent successful PTCA for LAD lesions and follow-up coronary angiography (18 patients with restenosis [Group-R], 35 patients without restenosis [Group-N]). We searched localized color aliasing corresponding to local flow acceleration to obtain coronary flow velocity at PTCA sites in the LAD. When localized aliasing was detected, we measured coronary flow velocity at the aliasing (stenotic site) and the prestenotic site. RESULTS: Using TTCDE, it was possible to measure mean diastolic velocity (MDV) in the LAD in 41 (77%) of 53 patients (14 of 18 patients in Group-R; 27 of 35 patients in Group-N). Localized aliasing was displayed by color flow mapping in 14 (100%) of 14 patients in Group-R, and 15 (56%) of 27 patients in Group-N. Stenotic MDV in Group-R was significantly higher than that in Group-N (60.3 +/- 21.1 vs. 35.1 +/- 7.6 cm/s, p < 0.01), although prestenotic MDV did not differ between Group-R and Group-N (20.2 +/- 3.0 vs. 19.6 +/- 2.3 cm/s). There were significant differences in the prestenotic to stenotic MDV ratio between Group-R and Group-N (0.36 +/- 0.10 vs. 0.57 +/- 0.09, p < 0.001). Localized aliasing with the prestenotic to stenotic MDV ratio <0.45 as the optimal cutoff value had a sensitivity of 86% and a specificity of 93% for the presence of restenosis in LAD lesions. CONCLUSIONS: Detection of localized color aliasing and measurement of the prestenotic to stenotic MDV ratio in the LAD by TTCDE are useful in the noninvasive diagnosis of restenosis after PTCA for LAD lesions.

Aged↗

PubMed2000

Production of recombinant human midkine in yeast, Pichia pastoris.

Recombinant human midkine was expressed in the cells of Pichia pastoris under the control of the AOX1 gene promoter. The expression of midkine was efficiently induced by methanol in a high cell density fermentation. Approximately 0.3 g/l culture of midkine accumulated in the cells by 72 h after induction. When the cells were disrupted, midkine was recovered in an insoluble form, and was insoluble even in the presence of 7 M urea. The precipitate was dissolved in the buffer solution (pH 8) containing 8 M guanidine hydrochloride, 10 mM dithiothreitol, 1 mM EDTA and 50 mM Tris-Cl, and then, midkine was renatured by dialysis at high concentration against the buffer solution (pH 8) containing 0.5 M sodium chloride and 20 mM Tris-Cl. The renatured midkine was recovered using a SP-Sepharose column, and purified further by Heparin-Sepharose column chromatography. Approximately 64 mg/l culture of the purified midkine was obtained. The amino acid sequence of amino-terminus and the amino acid composition of midkine were the same as those of Met-midkine that has a methionine residue at the amino-teminus. Mass spectrometry of purified Met-midkine showed a mass of 13370.7 Da (average), almost the theoretical mass for it. The Met-midkine enhanced the proliferation of Chinese hamster ovary (CHO) cells.

Journal Article↗

PubMed2000

Control of genetic stability in Escherichia coli: the SbcB 3'-5' exonuclease suppresses illegitimate recombination promoted by the RecE 5'-3' exonuclease.

BACKGROUND: The Escherichia coli sbcB gene, which codes for a 3'-5' exonuclease, ExoI, is known to suppress illegitimate recombination. In contrast, the recE gene, which codes for a 5'-3' exonuclease, Exo VIII promotes joining between DNA ends having short stretches of homology. Therefore, it seems likely that the 3'-5' and 5'-3' exonucleases regulate genetic instability that is mediated by illegitimate recombination. However, there has been little evidence to substantiate the involvement of exonuclease activity in the promotion and suppression of illegitimate recombination. RESULTS: Using a plasmid system for the analysis of deletion formation, we first demonstrated that deletion formation is increased by the sbcA mutation, which activates the expression of RecE 5'-3' exonuclease. It is thought that DNA ends having 3'-single stranded overhangs are important for illegitimate recombination. Next, we found that a large supply of SbcB 3'-5' exonuclease suppresses the deletion formation enhanced by the RecE exonuclease. Moreover, the SbcB exonuclease even suppressed deletion formation in cells not expressing RecE exonuclease. CONCLUSION: We conclude that DNA ends with 3'-overhangs produced by 5'-3' dsDNA exonuclease activity are proficient for illegitimate recombination, while blunt DNA ends produced by 3'-5' ssDNA exonuclease activity are deficient for illegitimate recombination. Therefore, both exonucleases may play important roles in genetic stability by controlling end-joining between DNA molecules.

Base Sequence↗

PubMed2000

An approach to the removal of yeast specific O-linked oligo-mannoses from human midkine expressed in Pichia pastoris using site-specific mutagenesis.

Human midkine is expressed and secreted in the medium under the control of an AOX1 gene promoter in Pichia pastoris using its own secretion signal. The midkine precursor is properly processed to yield the correct amino-terminus of mature midkine. However, more than half of the product receives yeast specific mannosylations. The sites for the mannosylations were determined to be the three threonine residues in the carboxy-terminal region of human midkine. In order to obtain non-mannosylated midkine, alanine residues were substituted for the three threonine residues by site specific mutagenesis. HPLC and mass spectrometry confirmed that the mutant midkine contained almost no mannose residues. Despite the amino acid substitutions in the carboxy-terminal region, mutant human midkine, promoted CHO cell proliferation as well as normal midkine.

Amino Acid Sequence↗

PubMed1999

Inhibitory effect of TS-962 on the formation of early atherosclerotic lesions in high fat-fed hyperlipidemic hamsters.

The hypocholesterolemic and anti-atherosclerotic effect of TS-962, a specific ACAT inhibitor, was investigated in a hamster model fed a high fat diet containing 10% coconut oil and 0.05% cholesterol. Lipid accumulated atherosclerotic lesions were detected by using oil red O staining in the lesion-prone aortic arch. A high dose, estimated to be 15 mg/kg, of TS-962 decreased serum cholesterol to normal levels with reduction of liver cholesterol contents below normal levels, and as a consequence, entirely inhibited the lipid accumulation in the aortic arch. Furthermore, a low dose, estimated to be 1.5 mg/kg, of TS-962 remarkably inhibited aortic lipid accumulation by 73% compared with the control group, without changing either serum cholesterol level or liver cholesterol content. These findings suggest that TS-962 is effective in the primary prevention of atherosclerosis by directly suppressing the formation of foam cells in arteries.

Acetamides↗

PubMed1999

Up-regulation of low density lipoprotein receptor by a novel isobenzofranone derivative, MD-700.

Stimulatory effects of a novel isobenzofranone, MD-700, on low density lipoprotein (LDL) receptor activity were investigated in vitro and in vivo. MD-700 at 0.03 microg/ml elevated the expression of LDL receptor in HepG2 cells within 4 h. Corresponding to this, uptake of fluorescent labeled-LDL (3,3'-dioctadecylindocarbocyanine-LDL) by the cells increased linearly in time- and dose-dependent manner by MD-700 for up to 12 h. In the experiment using HepG2 cells transiently transfected with promoter-luciferase gene constructs, MD-700 increased luciferase activity in a dose-dependent manner from 0.03 to 0.1 microg/ml. In contrast, luciferase activity was not stimulated by MD-700 in construct with a deleted sterol regulatory element (SRE)-1, suggesting importance of SRE-1 in stimulation of the LDL receptor gene promoter by MD-700. Binding experiments on liver membranes from MD-700-treated hamsters showed about a 60% increase in 125I-labeled LDL binding. A Scatchard plot revealed that MD-700 increased the maximal binding without affecting binding affinity. In contrast to findings with an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, pravastatin, MD-700 had no effect on the sterol synthesis in hamster liver homogenates. These results suggest that MD-700 stimulates the expression of LDL receptor, presumably in a manner independent of change in sterol metabolism, and thereby promotes LDL clearance. Hypocholesterolemic actions of MD-700 in hamsters were then examined. MD-700 lowered serum cholesterol levels in hamsters fed normal chow or a high-fat diet. Fractionation of serum lipoproteins demonstrated that MD-700 selectively decreased LDL and very low density lipoprotein cholesterol. Dose-dependent decrease in serum cholesterol was also seen in hypercholesterolemic rats. Thus, the hypocholesterolemic action of MD-700 may be attributed to up-regulation of the LDL receptor, based on stimulation of the transcription of the LDL receptor gene. Although pravastatin stimulates LDL uptake and lowers serum cholesterol in a manner similar to that seen with MD-700, the mechanism responsible for hypocholesterolemic action appears to differ.

Animals↗

PubMed1998

Noninvasive assessment of significant left anterior descending coronary artery stenosis by coronary flow velocity reserve with transthoracic color Doppler echocardiography.

BACKGROUND: Coronary flow reserve has been considered an important diagnostic index of the functional significance of coronary artery stenosis. With Doppler technique, it has been assessed as the ratio of hyperemic to basal coronary flow velocity (coronary flow velocity reserve [CFVR]) by invasive or semiinvasive methods with a Doppler catheter, a Doppler guide wire, and a transesophageal Doppler echocardiographic probe. Recent technological advancement in transthoracic Doppler echocardiography (TTDE) provides measurement of coronary flow velocity in the distal portion of the left anterior descending coronary artery (LAD) and may be useful in the noninvasive CFVR measurement. The purpose of this study was to evaluate the value of CFVR determined by TTDE for the assessment of significant LAD stenosis. METHODS AND RESULTS: We studied 36 patients who underwent coronary angiography for the assessment of coronary artery disease. The study population consisted of 12 patients with significant LAD stenosis (group A) and 24 patients without significant LAD stenosis (group B). With TTDE, coronary flow velocities in the distal LAD were recorded at rest and during hyperemia induced by intravenous infusion of adenosine (0.14 mg x kg(-1) x min(-1)) under the guidance of color Doppler flow mapping. Adequate spectral Doppler recordings of coronary flow in the distal LAD for the assessment of CFVR were obtained in 34 of 36 study patients (94%). The peak and mean diastolic coronary flow velocities at baseline did not differ between groups A and B (23.6+/-10.3 versus 22.9+/-6.6 cm/s and 16.4+/-8.6 versus 14.5+/-4.0 cm/s, respectively). However, the peak and mean coronary flow velocities during hyperemia in group A were significantly smaller than those in group B (35.6+/-16.3 versus 54.2+/-16.3 cm/s and 24.7+/-13.1 versus 37.9+/-13.0 cm/s, respectively; P<.01). There were significant differences in CFVR obtained from peak and mean diastolic velocity between groups A and B (1.5+/-0.2 versus 2.4+/-0.4 and 1.5+/-0.2 versus 2.6+/-0.4, respectively; P<.001). A CFVR from peak diastolic velocity <2.0 had a sensitivity of 92% and a specificity of 82% for the presence of significant LAD stenosis. A CFVR from mean diastolic velocity <2.0 had a sensitivity of 92% and a specificity of 86% for the presence of significant LAD stenosis. CONCLUSIONS: CFVR determined by TTDE is useful in the noninvasive assessment of significant stenotic lesion in the LAD.

Adult↗

PubMed1998

HL-004, the ACAT inhibitor, prevents the progression of atherosclerosis in cholesterol-fed rabbits.

HL-004, N-(2,6-diisopropylphenyl) tetradecylthioacetamide, a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, was evaluated concerning the possible prevention of hyperlipidemia and atherosclerosis in 1% cholesterol-fed rabbits. HL-004 (0.2, 5 and 25 mg/kg) was orally administered once a day for 12 weeks. HL-004 inhibited the rise of total serum cholesterol at a dose of 5 mg/kg and over. In the thoracic aorta, HL-004 at the doses of 5 mg/kg and 25 mg/kg reduced the total cholesterol content by 56.3% and 84.2% compared with control, and decreased ACAT activity, dose-dependently. HL-004 also attenuated the development of aortic lesions. The area of atherosclerotic lesions was reduced by 30.3% with 5 mg/kg of HL-004 and 100% with 25 mg/kg. In this study, we suggest that the main reason for HL-004 preventing the progression of atherosclerosis is its hypocholesterolemic effect due to the inhibition of cholesterol absorption in the intestine.

Acetanilides↗

PubMed1998

The ACAT inhibitor HL-004 inhibits cholesterol absorption and lowers serum cholesterol in rats.

1. HL-004 decreased absorption of cholesteryl ester from the intestine into the lymph in a rat lymph-fistula model. 2. HL-004 reduced serum cholesterol level in acute cholesterol-fed rats. 3. HL-004 simultaneously decreased hepatic cholesteryl ester content and increased free cholesterol in cholesterol-fed rats. 4. These findings suggest that: (1) the hypocholesterolemic effect of HL-004 is principally due to inhibition of cholesterol absorption via inhibition of ACAT in the intestine; and (2) changes in hepatic cholesterol metabolism due to direct inhibition by HL-004 of hepatic ACAT may account in part for reduction of serum cholesterol level by HL-004.

Absorption↗

PubMed1998

Noninvasive assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery by Doppler echocardiography: comparison with invasive technique.

OBJECTIVES: The purpose of this study was to evaluate whether transthoracic Doppler echocardiography (TTDE) can reliably measure coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD) in the clinical setting. BACKGROUND: Coronary flow velocity measurement has provided useful clinical and physiologic information. Advancement in TTDE provides noninvasive measurement of CFV and CFVR in the distal LAD. METHODS: In 23 patients, CFV in the distal LAD was measured by TTDE (5 or 3.5 MHz) under the guidance of color Doppler flow mapping at the time of Doppler guide wire (DGW) examination. Coronary flow velocity in the distal LAD were measured at baseline and hyperemic conditions (intravenous administration of adenosine 0.14 mg/kg/min) by both TTDE and DGW techniques. Coronary flow velocity reserve was defined as the ratio of peak hyperemic to basal averaged peak velocity in the distal LAD. RESULTS: Clear envelopes of basal and hyperemic CFV in the distal LAD were obtained in 18 (78%) of 23 study patients by TTDE. There were excellent correlations between TTDE and DGW methods for the measurements of CFV (averaged peak velocity: r=0.97, y=0.94x + 0.40; averaged diastolic peak velocity: r=0.97, y=0.94x + 0.69; systolic peak velocities: r=0.97, y=0.91x + 0.87; diastolic peak velocity: r=0.98, y=0.95x + 1.10). Coronary flow velocity reserve from TTDE correlated highly with those from DGW examinations (r=0.94, y=0.95x + 0.21). CONCLUSIONS: Noninvasive measurement of CFV and CFVR in the distal LAD using TTDE accurately reflects invasive measurement of CFV and CFVR by DGW method.

Adenosine↗

PubMed1998

Stimulation of cholesterol release from rabbit foam cells by the action of a new inhibitor for acyl CoA:cholesterol acyltransferase (ACAT), HL-004.

A new inhibitor of acyl CoA:cholesterol acyltransferase (ACAT), HL-004 [N-(2, 6-diisopropylphenyl)tetradecylthioacetamide], suppressed the synthesis of cholesterol [14C]oleate at 10(-9) approximately 10(-7) M in a concentration-dependent manner in both THP-1 cell-derived macrophages and foam cells prepared from aortic intima of rabbits fed a high cholesterol diet. Incorporation of [3H]cholesterol oleate-beta very low density lipoproteins was not inhibited by HL-004 at 10(-9) approximately 10(-7) M. Release of radioactivity from the cells loaded with [3H]cholesterol oleate-beta very low density lipoproteins was increased by the inhibition of ACAT activity with HL-004. HL-004 did not affect on acid and neutral cholesterol esterases. As a result, cholesterol ester content in foam cells decreased. These data suggested that HL-004 decreases cholesterol ester in foam cells by increasing the release of cholesterol and therefore might suppress atherosclerotic lesions.

Acetanilides↗

PubMed1998

[Assessment of coronary flow reserve in patients with hypertrophic cardiomyopathy using transthoracic color Doppler echocardiography].

Abnormal coronary flow pattern and coronary vasodilator reserve have been identified in patients with hypertrophic cardiomyopathy (HCM) using invasive techniques. The characteristics of coronary flow velocity and coronary flow reserve were evaluated by noninvasive-recording of coronary flow velocity in the distal portion of the left anterior descending coronary artery in 7 patients with HCM and 7 normal subjects using transthoracic color Doppler echocardiography. Coronary flow velocity was measured at rest and during intravenous infusion of adenosine triphosphate (0.15 mg/kg/min). Diastolic peak velocity, diastolic mean velocity, the time from the beginning of diastole to peak velocity (TVP) and velocity half time from peak velocity was measured in each group. Coronary flow reserve was obtained as the ratio of hyperemic mean velocity to resting mean velocity. TVP was significantly prolonged in the patients with HCM compared with the normal subjects (159 +/- 38 vs 103 +/- 54 msec, p < 0.05). Velocity half time was significantly shorter in the patients with HCM compared with the normal subjects (304 +/- 138 vs 451 +/- 109 msec, p < 0.05). Although diastolic mean velocity during hyperemia was not different between the 2 groups (62 +/- 8 vs 70 +/- 19 cm/sec), diastolic mean velocity at rest was significantly higher in the patients with HCM than in the normal subjects (39 +/- 6 vs 26 +/- 7 cm/sec, p < 0.01). Therefore, coronary flow reserve was significantly lower in the patients with HCM than in the normal subjects (1.6 +/- 0.4 vs 2.7 +/- 0.4, p < 0.001). There was a good correlation between diastolic mean velocity and the ratio of interventricular septal to posterior left ventricular wall thickness (y = 0.024x + 0.46, r = 0.75). Transthoracic assessment of coronary flow velocity using color Doppler echocardiography reveals that coronary flow reserve is reduced in patients with HCM because of increased baseline resting diastolic mean velocity.

Cardiomyopathy, Hypertrophic↗

PubMed1996

The hypolipidemic action of the ACAT inhibitor HL-004 in hamsters fed normal chow.

1. A novel ACAT (acyl-CoA: cholesterol acyltransferase) inhibitor, HL-004, exhibited a strong inhibitory effect on the hepatic and intestinal ACAT, but was less effective on the adrenal ACAT in vitro. 2. HL-004 selectively decreased serum VLDL cholesterol, and inhibited hepatic ACAT activity in hamsters fed normal chow. 3. These results suggest that the cholesterol-lowering effect of HL-004 can be attributed to a decrease in hepatic VLDL secretion via inhibition of ACAT.

Acetanilides↗

PubMed1996

Hypolipidemic effect of taurine in stroke-prone spontaneously hypertensive rats.

The hypolipidemic and antiatherosclerotic effects of taurine were investigated in genetically hypertensive rats: strokeprone spontaneously hypertensive rats (SHRSP). SHRSP were fed a hypercholesterolemic (HC) diet supplemented with 3% taurine for 50 days, and serum cholesterol was monitored. Cholesterol content and enzymatic activity responsible for cholesterol synthesis and metabolism were also determined in the liver, aorta, and intestine. Taurine prevented increases in the cholesterol level of the serum, liver, and aorta induced by a HC diet. Severe fat deposits of the mesenteric arteries induced by a HC diet were improved by the taurine treatment, showing the hypolipidemic and antiatherosclerotic effects of taurine. Taurine enhanced the activity of cholesterol 7 alpha-hydroxylase, a rate-limiting enzyme of bile acid synthesis, and stimulated bile acid production. These results suggest that taurine stimulates bile acid synthesis, which is closely related to the enhancement of cholesterol 7 alpha-hydroxylase activity, and thereby reduces serum cholesterol. In addition, a decrease in the intestinal acyl CoA:cholesterol acyltransferase activity by taurine suggests that the inhibition of cholesterol absorption may also be related to the hypolipidemic effect of taurine, in part.

Animals↗

PubMed1996

Effect of the ACAT inhibitor, HL-004, on cholesterol metabolism in macrophages.

The effects of a novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor, HL-004, on cholesterol metabolism were examined in mice peritoneal macrophages. Cholesteryl ester-rich foam cells were induced by incubating macrophages with acetylated LDL. HL-004 prevented the accumulation of cholesteryl ester in the presence of the cholesterol acceptor, HDL. In the absence of HDL, HL-004 generated large amounts of free cholesterol in the cell. Moreover, HL-004 stimulated the efflux of cholesterol from preestablished foam cells in the presence of HDL. These results suggest that the inhibition of foam cell formation and the stimulation of foam cell regression by HL-004 are attributed to intracellular ACAT inhibition, and that HL-004 would be expected to exhibit an antiatherosclerotic effect through direct action on arterial wall.

Acetanilides↗