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At least 811 records · Page 45Linked to original sources
PubMed1993

An anion exchanger mediates bile acid transport across the placental microvillous membrane.

Microvillous membrane vesicles from the term human placental syncytiotrophoblast were used to characterize further the properties of a transport mechanism for bile acids. Taurocholate (TC) uptake into an osmotically reactive intravesicular space was temperature dependent and independent of sodium. TC uptake (2 microM) was markedly inhibited by 250 microM taurine and glycine-conjugated cholate and chenodeoxycholate and unconjugated cholate but not by chenodeoxycholate, deoxycholate, etianic acid, bromosulfophthalein, pyruvate, lactate, alanine, or taurine. The initial rate of TC uptake was inhibited significantly by the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) but was not inhibited significantly by 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid, amiloride, or furosemide. Preincubation of vesicles with DIDS in the presence of TC partially blocked the action of the inhibitor. Efflux of 5 microM TC from membrane vesicles was stimulated by the presence of 50 microM TC in the incubation media. Basal as well as transstimulated TC efflux was inhibited by DIDS. The initial rate of TC influx followed saturation kinetics with an apparent Michaelis constant of 112 +/- 23 microM and maximal velocity of 2.01 +/- 0.19 nmol.mg protein-1.min-1. When the transmembrane electrical potential difference across the brush-border membrane vesicles was altered by external anion replacement or by valinomycin-induced K+ diffusion potentials, TC uptake was not significantly affected. DIDS-sensitive TC uptake was stimulated two-to threefold by an outwardly directed hydroxyl gradient (pH 7.7in/5.5out) compared with TC influx under pH-equilibrated conditions (pH 7.7in/7.7out). These studies are consistent with an electroneutral anion-exchange mechanism that mediates transfer of conjugated bile acids across the microvillous membrane of the syncytiotrophoblast.

Anion Exchange Resins↗
PubMed1993

Electrogenicity of Na-coupled bile salt transport in isolated rat hepatocytes.

The importance of membrane voltage in uptake of bile salts into hepatocytes is not known. Electrogenicity of the primary bile salt transport process, Na-bile salt cotransport, has been difficult to determine because the large K and Cl conductances of the sinusoidal membrane (GK and GCl, respectively) obscure any transport associated currents. In the present study hepatocytes were treated to reduce these membrane conductances and electrogenic entry of taurocholate and glycocholate was demonstrated. Intracellular voltage and resistance changes resulting from bile salt transport were measured in hepatocytes in which GK and GCl were blocked by impalement with Na acetate microelectrodes and external exposure to quinine (400 microM). This increased the cell input resistance from 153 +/- 17 to 230 +/- 17 M omega (n = 14, P < 0.001). Under these conditions, exposure to 100 microM of taurocholate or glycocholate produced Na-dependent depolarizations of 3.0 +/- 0.5 and 4.2 +/- 0.8 mV, respectively. These correspond to transport currents of 13.9 and 7.6 pA/cell, which are comparable to those predicted from known [3H]taurocholate uptake rates if one positive charge enters the cell with each bile salt molecule. Although uptake of these two bile salts was electrogenic, this was not the case for all bile salts. Na-dependent transport of taurodehydrocholate, which occurs at similar rates to that for taurocholate, produced no voltage change. The unconjugated bile salts cholate and ursodeoxycholate also produced no measurable voltage or resistance changes. In conclusion, Na-dependent uptake of taurocholate and glycocholate is electrogenic, whereas uptake of taurodehydrocholate, ursodeoxycholate, and cholate is predominantly electroneutral.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1993

Characterization of bumetanide transport in isolated skate hepatocytes.

The uptake of [3H]bumetanide was studied in isolated skate hepatocytes in an albumin-free elasmobranch Ringer solution and compared with the uptake of bile acids in the presence of other cholephilic organic anions. [3H]bumetanide uptake was energy dependent, temperature sensitive, and exhibited saturation kinetics. In contrast to taurocholate and cholate, which are transported only by Na(+)-independent mechanisms, removal of Na+ reduced the maximal uptake rate (Vmax) for bumetanide from 404 +/- 80 to 230 +/- 47 pmol.mg-1 x min-1 without a change in the apparent Michaelis constant (Km). The apparent Km for the Na(+)-dependent portion of bumetanide uptake was 58 +/- 24 microM, and Vmax was 151 +/- 38 pmol.min-1 x mg-1. Taurocholate (100 and 200 microM) inhibited Na(+)-independent bumetanide transport competitively but was a noncompetitive inhibitor for Na(+)-dependent bumetanide uptake. Furosemide (100 microM) and two bumetanide analogues, PF-3034 (500 microM) and PF-2203 (500 microM), preferentially inhibited the Na(+)-dependent bumetanide uptake system, whereas cholate (100 microM) and probenecid (100 microM) preferentially inhibited Na(+)-independent bumetanide transport. The sulfhydryl (SH) reagents N-ethylmaleimide, 2,2'-dithio-bis(5-nitropyridine), and p-chloromercuribenzenesulfonic acid (PCMBS) inhibited both bile acid and bumetanide uptake. Dithiothreitol (500 microM) completely reversed the PCMBS-induced inhibition of bumetanide uptake. These results indicate that bumetanide is transported into hepatocytes of the small skate, Raja erinacea, by both Na(+)-dependent and Na(+)-independent mechanisms; the latter is shared by bile acids and probably sulfobromophthalein and other organic anions. Their uptake requires free SH groups.

Animals↗
PubMed1993

Interaction of bumetanide derivatives with hepatocellular bile acid uptake.

The loop diuretic bumetanide is an organic monocarboxylic organic anion assumed to be transported into hepatocytes by a transport system for bile acids. The structural requirements of 22 bumetanide analogues were analyzed for an interaction with bile acid uptake into isolated rat hepatocytes. Whereas bumetanide inhibited the hepatocellular uptake of [14C]cholate to the same degree as its own uptake, derivatization altered affinity and specificity and yielded compounds that selectively inhibited either cholate or taurocholate uptake or uptake of both. No correlation was found between the diuretic potency of bumetanide derivatives, reflecting the affinity to the Na(+)-K(+)-Cl- cotransporter, and their affinity to hepatic bile salt transport. Computer-aided model building combined with the calculation of potential energy maps showed a strictly amphipathic charge separation in bumetanide analogues as in bile acids. Ranking bumetanide compounds by their mean inhibitory concentration values, inhibition constants, and their type of competition, we conclude that at least three binding domains in the proteins are essential for recognition by bile acid transporters, namely two hydrophobic and an anionic side, and that for the anionic binding region a carbonyl atom in the ligands as an electron donor group is sufficient for ligand interaction.

Animals↗
PubMed1999

Cholic acid aids absorption, biliary secretion, and phase transitions of cholesterol in murine cholelithogenesis.

Cholic acid is a critical component of the lithogenic diet in mice. To determine its pathogenetic roles, we fed chow or 1% cholesterol with or without 0.5% cholic acid to C57L/J male mice, which because of lith genes have 100% gallstone prevalence rates. After 1 yr on the diets, we measured bile flow, biliary lipid secretion rates, hepatic cholesterol and bile salt synthesis, and intestinal cholesterol absorption. After hepatic conjugation with taurine, cholate replaced most tauro-beta-muricholate in bile. Dietary cholic acid plus cholesterol increased bile flow and biliary lipid secretion rates and reduced cholesterol 7alpha-hydroxylase activity significantly mostly via deoxycholic acid, cholate's bacterial 7alpha-dehydroxylation product but did not downregulate cholesterol biosynthesis. Intestinal cholesterol absorption doubled, and biliary cholesterol crystallized as phase boundaries shifted. Feeding mice 1% cholesterol alone produced no lithogenic or homeostatic effects. We conclude that in mice cholic acid promotes biliary cholesterol hypersecretion and cholelithogenesis by enhancing intestinal absorption, hepatic bioavailability, and phase separation of cholesterol in bile.

Absorption↗
PubMed1976

Uptake of bile acids by perfused rat liver.

The uptake of 14C-labeled cholic, taurocholic, and chenodeoxycholic acid by the perfused rat liver was studied to characterize the mechanism responsible for hepatic uptake of bile acids. A rapid-injection multiple indicator-dilution technique and the three-compartment model of Goresky were employed. The kinetics of hepatic uptake of the three bile acids could be described by the Michaelis-Menten equation. The maximal uptake velocities (Vmax) were 24.9 +/- 2.2 (mean +/- SD), 20.8 +/- 1.2, 1.2, and 11.4 +/- 0.9 nmol/s-g liver for cholic, taurocholic, and chenodeoxycholic acid, respectively. The corresponding apparent half-saturation constants (Km) were 526 +/- 125, 258 +/- 43, and 236 +/- 48 nmol/g liver. Competitive inhibition could be demonstrated between cholate and taurocholate as well as between cholate and chenodeoxycholate. Substitution of 94% of the Na+ in the perfusion medium decreased the Vmax and the apparent Km of taurocholate uptake by 68 and 55%, respectively. These findings are consistent with the hypothesis that bile acids are taken up into the hepatocyte by Na+-dependent carrier-mediated transport.

Animals↗
PubMed1976

Bile acid conjugation in fetal hepatic organ cultures.

A new technique has been developed in which mammalian fetal liver can be maintained in organ culture for prolonged periods with intact structure and function. Near-term rat fetal liver explants were incubated in vitro for periods of up to 3 wk with preservation of normal cellular morphology and intercellular (organ) relationships. [14C]cholate was incorporated into tissue and medium conjugates at a constant rate during 21 days in vitro. During a 24-h incubation with radioactively labeled cholic acid, bile acid conjugates accumulated in tissues to a maximum value by 6 h and maintained this value through 24 h. During the same 24-h incubation with [14C]cholate, conjugates were secreted into the medium at a constant rate. Addition of 8 X 10(-4) M taurine to the medium during a 4-day incubation produced a threefold enhancement in the rate of conjugate formation in tissues and medium. Enhanced conjugation in the presence of additional taurine was due almost entirely to increased taurocholate formation and no significant difference was observed in the amount of glycocholate formed. Exposure of explants to 3.6 X 10(-4) M cycloheximide for prolonged periods resulted in inhibition of conjugate formation, but when this concentration of cycloheximide was maintained for only 24 h a significantly (P less than 0.001) increased rate of conjugate formation was observed. The results indicate that metabolic processes in the organ-culture system are in a state of dynamic equilibrium and that morphologic integrity and specific hepatocytic function are maintained after 21 days in vitro. Preferential taurocholate formation was demonstrated in rat fetal liver, and the data suggest that glycine and taurine interact with separate enzymatic systems in bile acid conjugation. The possible mechanisms that mediate the effect of cycloheximide are discussed.

Animals↗
PubMed2003

Sodium-dependent methotrexate carrier-1 is expressed in rat kidney: cloning and functional characterization.

Previous Northern blot studies suggested strong expression of a homolog to the sodium-dependent hepatocellular methotrexate transporter in the kidneys. Here, we report on the cloning of the cDNA for the renal methotrexate carrier isoform-1 (RK-MTX-1) and its functional characterization. Sequencing revealed 97% homology to the rat liver methotrexate carrier with an identical open reading frame. Differences were located in the 5'-untranslated region and resulted in the absence of putative regulatory elements (Barbie box, Ah/ARNT receptor) identified in the cDNA for the hepatocellular carrier. For functional characterization, MTX-1 cDNA was stably expressed in Madin-Darby canine kidney (MDCK) cells. A sodium-dependent transport of methotrexate with a K(m) of 41 microM and a V(max) of 337 pmol.mg protein(-1).min(-1) was observed. This uptake was blocked by the reduced folates dihydro- and tetrahydrofolate as well as by methotrexate itself. Folate was inhibiting only weakly, whereas 5-methyltetrahydrofolate was a strong inhibitor. Further inhibitors of the methotrexate transport included the bile acids cholate and taurocholate and xenobiotics like bumetanide and BSP. PAH, ouabain, bumetanide, cholate, taurocholate, and acetyl salicylic acid were tested as potential substrates. However, none of these substances was transported by MTX-1. Furthermore, expression of RK-MTX-1 in MDCK cells enhanced methotrexate toxicity in these cells fivefold. Analysis of a fusion protein of RK-MTX-1 and the influenza virus hemagglutinin epitope by immunoblotting revealed a major band at 72 kDa within the cell membrane but not in the soluble fraction of transfected MDCK. Indirect immunofluorescence staining revealed an exclusive localization of the carrier in the plasma membrane, and by confocal laser-scanning microscopy we were able to demonstrate that the protein is expressed in the serosal region of MDCK tubules grown in a morphogenic collagen gel model.

Animals↗
PubMed2003

Regulation of renal tubular bile acid transport in the early phase of an obstructive cholestasis in the rat.

BACKGROUND/AIMS: In obstructive liver diseases, urinary excretion of bile acids is markedly enhanced. The mechanism of this effect is not entirely clear. The aim of the present study was to assess the glomerular and tubular factors involved in the renal handling of bile acids during the early phase of an obstructive cholestasis induced by a 24-hour bile duct ligation in rats. METHODS: In addition to conventional clearance experiments, taurocholate transport was studied on proximal tubular cells freshly isolated from rat kidneys. The expression of the taurocholate transport protein was determined in these cells by immunoblotting. RESULTS: Glomerular filtration rate and arterial blood pressure were not significantly affected by the cholestasis induced. The (3)H-taurocholate and (3)H-cholate clearances significantly increased whereas the fractional tubular reabsorption rates of these bile acids significantly fell. Probenecid did not affect the (3)H-taurocholate and (3)H-cholate clearances. By employing S0960, a specific inhibitor of the sodium-dependent bile salt transporter ASBT, it could be shown that this transporter mediates (3)H-taurocholate uptake into the proximal tubular cells. The bile duct ligation caused a significant decrease of the V(max) value of the taurocholate transporter indicating a downregulation of this transporter in cholestasis. The downregulation occurred without a change of the ASBT protein content of the proximal tubular cells. CONCLUSION: The results demonstrate that there is a functional adaptive downregulation of renal tubular bile acid transport enhancing renal clearance of bile acids during the early phase of an obstructive cholestasis.

Animals↗
PubMed1975

Increased sulfation of lithocholate in patients with cholesterol gallstones during chenodeoxycholate treatment.

Chenodeoxycholate was administered to 13 patients with cholesterol gallstones. During the treatment period the bile composition changed markedly. Chenodeoxycholate increased from 42.9% of the total bile salts before treatment to 79.3% after 8 weeks of treatments. Ursodeoxycholate increased from 2.3 to 12.6% and lithocholate from 1.1 to 3.3%. In contrast, cholate decreased from 40.3% of the total bile salts to 3.1% and deoxycholate decreased from 12.5 to 2.5%. Less than 5% of chenodeoxycholate, ursodeoxycholate, cholate and deoxycholate in bile were sulfate esters. In contrast, considerable amounts of lithocholate were sulfated. The sulfation of lithocholate increased from 32.8% of the total lithocholate before treatment to 73.9% after 8 weeks of treatment. Sulfated lithocholate is more rapidly eliminated in feces and urine than the nonsulfated compound. Furthermore, sulfated lithocholate is less toxic. Therefore, the increase in the sulfation of lithocholate observed in most of our patients represents a protective mechanism.

Aged↗
PubMed1977

The effects of cholecystectomy on the bile salt pool of the syrian hamster.

The half-life, distribution, size and composition of the bile salt pool were determined in intact and cholecystectomized Syrian hamsters. Cholecystectomy had no effect on the half-life of either the cholate or chenodeoxycholate pool. Fasting in intact hamsters resulted, as expected, in a shift of bile salts from the small intestine, cecum and liver to the gallbladder. In cholecystectomized hamsters there was a moderate shift of salts from the liver and small intestine to the cecum. Cholecystectomy had no significant effect on the size of the total bile salt pool. The total bile salt pool size of fed and fasted intact hamsters was the same; fasting in cholecystectomized hamsters resulted in a large decrease in the pool. There was no significant difference in the bile salt pool composition of intact and cholecystectomized hamsters, and hamsters were shown to efficiently convert deoxycholate to cholate.

Animals↗
PubMed1984

Investigations on the toxicity of bile salt solutions, Capmul 8210 and a bile salt-EDTA solution for common bile duct perfusion in dogs.

The following perfusion media for dissolving bile duct calculi were infused via a cutaneobiliary tube into the biliary tract of 12 mongrel dogs: 4.3% cholate solution, 0.34% chenodeoxycholate solution, Capmul, GMOC (special formulation of Capmul), BA-EDTA and 0.9% saline. Infusion lasted 50 h. Postmortem examination revealed hemorrhagic, partly phlegmonous cholangitis, acute duodenitis, necrosis and abscesses in the liver. The lesions were most pronounced after the cholate solution and with Capmul and GMOC, but were only detected to a slight extent after BA-EDTA and the chenodeoxycholate solution. 0.9% saline had no side effects. The investigations could demonstrate that it is the very irrigation media that today are recommended for treatment of bile duct stones in patients, that cause considerable morphologic side effects. The alternating administration of an EDTA solution with a Capmul preparation may diminish local toxicity of the latter.

Animals↗
PubMed2005

Diet and murine atherosclerosis.

Lipid-enriched diets are often used to induce or accelerate the rate of atherosclerotic lesion development in murine models of atherosclerosis. It appears that the induction of persistent hypercholesterolemia to levels > or approximately to 300 mg/dL is required for the development of experimental atherosclerosis in the mouse. A variety of different diets have been used that vary in the level of cholesterol, the level and type of fatty acid, and the absence or presence of cholate. Each of these components as well as the protein source has been shown to influence lipoprotein level and/or atherosclerosis, with dietary cholesterol being the major proatherogenic component. In some instances the effects of these components on the expression of hepatic genes relevant to lipid homeostasis has been observed. An appreciation of the effect of the differences in diet composition on these processes is important to compare results from different atherosclerosis studies, so the composition of the diets used should always be reported or referenced. Cholate should not be used unless its effects are being specifically investigated.

Animal Feed↗
PubMedDate not supplied

Radioimmunoassay of apolipoprotein a-ii.

A double antibody radioimmunoassay was developed for apolipoprotein A-II (apo A-II), one of the two major apoproteins of human high density lipoproteins (HDL). Apo A-II contains two identical polypeptide chains linked by a disulfide bond. A specific antiserum was raised in sheep. Tracer apo A-II was radiolabeled with 125I by the Bolton-Hunter technique. Reduction and carboxymethylation of apo A-II approximately doubled its immunoreactivity. Since normal sera were found to contain small amounts of monomeric apo A-II, this represented one potential source of error in the radioimmunoassay. Inclusion of 0.1 M sodium cholate in the assay system, however, led to identical immunoreactivity of dimeric apo A-II and the reduced and carboxymethylated protein. Radioimmunoassay using sheep anti-apo A-II detected 75% to 85% of the apo A-II contained in serum or HDL. Masked antigenic sites could be exposed by organic solvent extraction or, more simply, by dilution of serum samples in the buffer containing 0.1 M sodium cholate. Serum levels of apo A-II were measured in a population of consecutively and prospectively selected free-living subjects between 30 to 69 years of age. Levels were significantly (p less than 0.005) higher in females (n = 201; 42.0 +/- 10.3 mg/dl) than in males (n = 189; 39.0 +/- 8.4 mg/dl). Serum apo A-II levels correlated significantly with HDL-cholesterol levels but less strongly than apo A-I, the other major HDL apoprotein.

Adult↗
PubMed1971

Bile acid synthesis in the isolated, perfused rabbit liver.

These experiments were carried out to demonstrate the usefulness of the perfused rabbit liver for studies of bile acid metabolism, and to determine the rate-limiting enzyme of bile acid synthesis. Rabbits were fed a semisynthetic diet, with or without the addition of 1% cholestyramine, under controlled conditions. At the end of 2-5 wk, the livers were removed and perfused for 2.5 hr employing various (14)C-labeled precursors to measure de novo cholic acid synthesis. The livers were then analyzed for cholesterol, and the bile collected during the perfusion was analyzed for cholesterol and bile acids. Control bile contained, on the average, 0.34 mg of glycocholate, 7.4 mg of glycodeoxycholate, and 0.06 mg of cholesterol. After cholestyramine treatment of the donor rabbits, the bile contained 3.3 mg of glycocholate, 3.7 mg of glycodeoxycholate, and 0.05 mg of cholesterol. It was assumed that in cholestyramine-treated animals the enterohepatic circulation of the bile acids had been interrupted sufficiently to release the feedback inhibition of the rate-controlling enzyme of bile acid synthesis. Therefore, a given precursor should be incorporated into bile acids at a more rapid rate in livers of cholestyramine-treated animals, provided that the precursor was acted upon by the rate-controlling enzyme. It was found that the incorporation of acetate-(14)C, mevalonolactone-(14)C, and cholesterol-(14)C into cholate was 5-20 times greater in the livers of cholestyramine-treated animals than in the controls. In contrast, there was no difference in the incorporation of 7alpha-hydroxycholesterol-(14)C into cholate regardless of dietary pretreatment. It was concluded that given an adequate precursor pool, the 7alpha-hydroxylation of cholesterol is the rate-limiting step in bile acid formation.

Acetates↗
PubMed1972

Bile acid synthesis in man: metabolism of 7 -hydroxycholesterol- 14 C and 26-hydroxycholesterol- 3 H.

The pathways of bile acid synthesis in man were evaluated by studying the metabolism of 7alpha-hydroxycholesterol-4-(14)C and 26-hydroxycholesterol-16, 22-(3)H administered parenterally to individuals requiring external biliary drainage. Techniques for the identification of metabolites were thin-layer chromatography, column chromatography, gas-liquid chromatography with stream splitting, and crystallization to constant specific activity. It was found that both compounds were rapidly metabolized to bile acids and excreted in bile. Of the total radioactivity recovered in bile as bile acids, 87% of the 26-hydroxycholesterol-(3)H and 90% of the 7alpha-hydroxycholesterol-(14)C was found to be metabolized to both chenodeoxycholate and cholate. Compared to 7alpha-hydroxycholesterol, a greater proportion of 26-hydroxycholesterol was found to be metabolized to chenodeoxycholate. These findings indicate that both 7alpha-hydroxycholesterol and 26-hydroxycholesterol can be intermediates in the metabolism of cholesterol to bile acids in man. The observation that conversion to cholate takes place less readily after C-26 hydroxylation is consistent with previous findings in other species.

Autoradiography↗
PubMed1986

Hepatocellular uptake of sulfobromophthalein and bilirubin is selectively inhibited by an antibody to the liver plasma membrane sulfobromophthalein/bilirubin binding protein.

To clarify sulfobromophthalein (BSP) and bilirubin uptake mechanisms, isolated rat hepatocytes were incubated with [35S]BSP. The initial uptake velocity (V0), determined from the first, linear portion of the cumulative uptake curve, was saturable (Michaelis constant [Km] = 6.2 +/- 0.5 microM; Vmax = 638 +/- 33 pmol X min-1 per 10(5) hepatocytes), maximal at 37 degrees C and pH 7.4, and competitively inhibited by bilirubin, but not by taurocholate, cholate, or oleate. Preloading with unlabeled BSP led to trans-stimulation of V0. Sodium substitution or pretreatment of hepatocytes with ouabain or metabolic inhibitors had no effect on V0; trypsin reduced V0 by 39% (P less than 0.001). A rabbit antiserum to the rat liver plasma membrane (LPM)-BSP/bilirubin binding protein selectively reduced V0 of 5 microM [35S]BSP and [14C]bilirubin by 41 and 42%, respectively (P less than 0.01); uptakes of [3H]oleate, [3H]cholate and [3H]taurocholate were not affected. Hence, the LPM-BSP/bilirubin binding protein plays a role in the carrier-mediated uptake of BSP and bilirubin by hepatocytes.

Animals↗
PubMed1996

A noninjury, diet-induced swine model of atherosclerosis for cardiovascular-interventional research.

To investigate whether atherosclerotic vascular disease in the microswine model can be induced by atherogenic diet alone and does not require balloon injury or endothelial denudation as widely stated in the literature, 28 female Yucatan microswine were fed a high-fat, high-cholesterol diet, including 2% sodium cholate, for an average of 310 +/- 13 days. Four control swine were placed on a regular diet for an average of 287.2 +/- 7.8 days. Selective coronary arteriography and morphologic and histologic studies were performed at the end of this period. Coronary arteries were fixed in vivo by pressure perfusion of formalin. Angiograms and sequential histologic sections were reviewed by a double-blind team. The angiography did not show apparent disease in all vessels but generally revealed mild irregularity. Quantitatively, there was a 30.5 +/- 3.5% stenosis (mean +/- standard error, P < 0.05 vs. control) in left anterior descending (LAD), 40.7 +/- 4.5% of stenosis in right coronary artery (RCA) (P < 0.01 vs. control), and 24.8 +/- 3.7% of stenosis in left circumflex artery (LCX). The lesions were eccentric in 95% of LCA, 95.8% of RCA, and 75% of LCX, and the remainder were concentric lesions. Typical lesions were characterized by significant intimal proliferation, cholesterol clefts, necrotic cores, heavy extracellular fat deposition, and calcification. Control animals had only occasional, minimal intimal lipid deposition in coronary arteries. These findings suggest that the Yucatan microswine is an ideal coronary atherosclerosis animal model for vascular research. Lesions can be induced by atherogenic diet alone. Cholesterol uptake is increased by adding sodium cholate to the feed. Moreover, balloon injury of the intima or media is not required to induce significant atherosclerotic lesions in coronary arteries.

Animals↗