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Biomedical subjects

A van Tol

Publications and source records attributed to A van Tol.

At least 37 records · Page 2Linked to original sources
PubMed2001

Role of phospholipid transfer protein and prebeta-high density lipoproteins in maintaining cholesterol efflux from Fu5AH cells to plasma from insulin-resistant subjects.

Plasma phospholipid transfer protein (PLTP) enhances the generation of prebeta-high density lipoproteins (HDL) that may act as initial acceptors of cellular cholesterol, and are likely to play an important role in the antiatherogenic process of reverse cholesterol transport. We examined the interrelationships between insulin resistance, the ability of plasma to stimulate cellular cholesterol efflux, HDL cholesterol, plasma PLTP activity and prebeta-HDL in 12 non-diabetic, non-smoking, normotriglyceridaemic men. Cholesterol efflux from Fu5AH cells to plasma, plasma lipoproteins, PLTP activity and prebeta-HDL formation as measured in incubated plasma were determined after a 12-h fast. Insulin sensitivity was assessed by a euglycaemic, hyperinsulinaemic clamp (M-value). HDL cholesterol was positively correlated with the M-value (r=0.65, p< 0.05), whereas plasma PLTP activity (r= -0.59, p <0.05) and prebeta-HDL in incubated plasma (r= -0.66, p<0.05) were negatively correlated with the M-value. Thus, the lower the insulin sensitivity, the lower was HDL cholesterol and the higher were plasma PLTP activity and prebeta-HDL. Cellular cholesterol efflux tended to be correlated with HDL cholesterol (r=0.55, p < 0.10) as well as with plasma PLTP activity (r=0.56, p<0.10) and was positively correlated with prebeta-HDL in incubated plasma (r=0.74, p<0.01). No positive correlation between the M-value and cellular cholesterol efflux was found (r= -0.34, ns). These preliminary results support the hypothesis that, despite a lower HDL cholesterol, the ability of plasma from insulin-resistant subjects to promote cellular cholesterol efflux is not impaired, as a consequence of a higher plasma PLTP activity and enhanced prebeta-HDL formation.

Adult↗
PubMed2001

Moderate alcohol consumption: effects on lipids and cardiovascular disease risk.

Light to moderate alcohol consumption is associated with a reduced risk of coronary heart disease, as well as ischaemic stroke and possibly type 2 diabetes. Epidemiological and physiological data are in favour of a causal relationship. Proposed protective mechanisms include the stimulation of HDL-mediated processes such as reverse cholesterol transport and antioxidative effects. More well-controlled studies are needed to provide a complete understanding of the complexity of the underlying physiological mechanisms.

Alcohol Drinking↗
PubMed2001

Hyperlipidemia and atherosclerosis associated with liver disease in ferrochelatase-deficient mice.

Erythropoietic protoporphyria (EPP) is an inherited disorder of heme synthesis caused by deficiency of the mitochondrial enzyme ferrochelatase. EPP in humans is associated with liver disease, hypertriglyceridemia, and a low level of high density lipoprotein (HDL) cholesterol. To explore consequences of ferrochelatase deficiency in lipid metabolism, we have analyzed hepatic lipid content and plasma lipoprotein levels in chow-fed BALB/c mice homozygous ( fch/fch) or heterozygous ( fch/1) for a point mutation in the ferrochelatase gene and in wild-type controls (1/1). Livers of fch/fch mice show bile duct proliferation and biliary fibrosis, but bile formation is not impaired. The free cholesterol content of fch/fch livers is significantly increased when compared with fch/1 and 1/1 livers. Plasma cholesterol in fch/fch mice (9.9 +/- 6.4 mM) is elevated when compared with fch/1 and 1/1 mice (2.9 +/- 0.2 and 2.5 +/- 0.3 mM, respectively), because of an increased cholesterol content in the very low density lipoprotein-sized fractions, whereas HDL cholesterol is reduced. The ratio of cholesteryl ester to free cholesterol is 4.3 +/- 0.6, 3.3 +/- 0.3, and 0.3 +/- 0.1 in the plasma of 1/1, fch/1, and fch/fch mice, respectively. The latter is not due to reduced lecithin:cholesterol acyltransferase activity in plasma of fch/fch mice but to the presence of lipoprotein-X (Lp-X), a particle composed of bile-type lipids usually seen only in cholestatic conditions. Expression of mdr2, essential for biliary phospholipid/cholesterol secretion, is increased in fch/fch livers. In spite of this, biliary phospholipid/cholesterol secretion is reduced relative to that of bile salts. It is postulated that an inability of bile salts to stimulate lipid secretion adequately leads to formation of Lp-X in this noncholestatic condition. Distinct atherosclerotic lesions were found in aged fch/fch mice.Thus, ferrochelatase deficiency in mice leads to liver disease associated with altered hepatic lipid metabolism, a characteristic hyperlipidemia, and development of atherosclerosis.-Bloks, V. W., T. Plösch, H. van Goor, H. Roelofsen, J. Baller, R. Havinga, H. J. Verkade, A. van Tol, P. L. M. Jansen, and F. Kuipers. Hyperlipidemia and atherosclerosis associated with liver disease in ferrochelatase-deficient mice. J. Lipid Res. 2001. 42: 41;-50.

Animals↗
PubMed2001

Alcohol consumption stimulates early steps in reverse cholesterol transport.

Alcohol consumption is associated with increased HDL cholesterol levels, which may indicate stimulated reverse cholesterol transport. The mechanism is, however, not known. The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol pathway: cellular cholesterol efflux and plasma cholesterol esterification. Eleven healthy middle-aged men consumed four glasses (40 g of alcohol) of red wine, beer, spirits (Dutch gin), or carbonated mineral water (control) daily with evening dinner, for 3 weeks, according to a 4 x 4 Latin square design. After 3 weeks of alcohol consumption the plasma ex vivo cholesterol efflux capacity, measured with Fu5AH cells, was raised by 6.2% (P < 0.0001) and did not differ between the alcoholic beverages. Plasma cholesterol esterification was increased by 10.8% after alcohol (P = 0.008). Changes were statistically significant after beer and spirits, but not after red wine consumption (P = 0.16). HDL lipids changed after alcohol consumption; HDL total cholesterol, HDL cholesteryl ester, HDL free cholesterol, HDL phospholipids and plasma apolipoprotein A-I all increased (P < 0.01). In conclusion, alcohol consumption stimulates cellular cholesterol efflux and its esterification in plasma. These effects were mostly independent of the kind of alcoholic beverage

Alcohol Drinking↗
PubMed2000

Conversion to mycophenolate mofetil in conjunction with stepwise withdrawal of cyclosporine in stable renal transplant recipients.

BACKGROUND: Mycophenolate mofetil (MMF) is now part of standard immunosuppression in the first phase after renal transplantation. A relevant question is if it can replace drugs such as cyclosporine (CsA) in the maintenance treatment, improving cardiovascular risk profile. METHODS: In 17 patients with a stable renal function (at least 6 months) posttransplantation, we studied the effect of CsA replacement by MMF. After starting MMF (1 g b.i.d.), CsA dosage was reduced from regular to low (median trough level 130 microg/L, respectively, 45 microg/L), followed by complete withdrawal, while prednisone (7.5 mg daily) was continued. We measured ambulatory blood pressure, glomerular filtration rate, renal plasma flow, renal vascular resistance, and metabolic factors at start and after 8 weeks on regular, low-dose CsA, respectively, no CsA with MMF and prednisone. RESULTS: Two patients dropped out after the switch to low-dose CsA/MMF, due to diarrhea in one and a steroid responsive rejection in the other. The complete switch from CsA to MMF was successful in all 15 patients and accompanied by a decrease in 24 hr systolic blood pressure (from 152+/-13 to 145+/-13 mmHg; P<0.01), diastolic blood pressure (93+/-9 to 89+/-12 mmHg; P<0.05), RVR (0.29+/-0.06 to 0.25+/-0.09 mmHg.ml/min; P<0.05), and an increase in glomerular filtration rate (46.6+/-8.8 to 58.0+/-10.5 ml/min; P<0.01) and renal plasma flow. Intermediate low density lipoprotein-cholesterol decreased (0.79+/-0.37 to 0.41+/-0.16 mmol/L; P<0.01). High density lipoprotein-cholesterol decreased, but remained in the safe range. After 1 year two patients stopped the MMF; one because of Kaposi's sarcoma and one because of recurrent infections CONCLUSIONS: The stepwise switch from CsA to MMF was safe and mostly successful, and had beneficial effects on blood pressure, glomerular hemodynamics, and lipid profile. Beneficial trends were already present after partial withdrawal of CsA.

Adult↗
PubMed2000

Low plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities in growth hormone deficient and acromegalic men: role in altered high density lipoproteins.

Growth hormone (GH) deficiency and acromegaly may be associated with increased cardiovascular risk. Little is known about alterations in high density lipoproteins (HDL) in these conditions. Lecithin:cholesterol acyl transferase (LCAT) has the ability to esterify free cholesterol (FC) in HDL. Cholesteryl ester transfer protein (CETP) is able to transfer cholesteryl esters (CE) from HDL to very low and low density lipoproteins (VLDL and LDL). During phospholipid transfer protein (PLTP)-mediated HDL remodelling, small pre beta-HDL particles are generated which serve as acceptors for cellular cholesterol and provide the initial LCAT-substrate. We documented plasma lipids, LCAT, CETP and PLTP activity levels as well as plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) in 12 adult men with acquired GH deficiency, 12 acromegalic men and 24 healthy male subjects. All GH deficient and acromegalic patients received conventional hormonal replacement therapy if necessary. VLDL + LDL cholesterol and plasma triglycerides were higher in GH deficient (P < 0.01 and P < 0.05) and acromegalic patients (P < 0.05 and P < 0.01) than in healthy subjects. HDL cholesterol and HDL CE were lower (P < 0.05 for both) and the HDL FC/CE ratio was higher (P < 0.01) in these patient groups compared to healthy subjects. Plasma LCAT, CETP and PLTP activity levels were lower in acromegalic patients (P < 0.01 for all) and CETP activity was lower in GH deficient patients (P < 0.01) compared to healthy subjects. Plasma EST and CET were decreased in both acromegalic (P < 0.01 for both) and GH deficient patients (P < 0.05 for both). Multiple regression analysis demonstrated independent negative relationships of plasma insulin-like growth factor I with plasma LCAT (P = 0.0001), CETP (P = 0.009) and PLTP activity levels (P = 0.021). Plasma LCAT (P = 0.0001) and CETP activity (P = 0.0001) were also negatively associated with (substitution therapy for) adrenal insufficiency. In conclusion, GH deficient and acromegalic patients show abnormalities in HDL, consistent with impaired LCAT action. Decreases in plasma EST and CET in such patients, as well as a low PLTP activity in acromegaly suggest that reverse cholesterol transport may be impaired, contributing to increased cardiovascular risk.

Acromegaly↗
PubMed2000

Decreased plasma cholesterol esterification and cholesteryl ester transfer in hypopituitary patients on glucocorticoid replacement therapy.

Cardiovascular risk is increased in hypopituitary patients. No data are available with respect to the effect of glucocorticoid replacement therapy on high density lipoproteins (HDL) metabolism in such patients. Plasma lecithin:cholesterol acyl transferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are important determinants of HDL remodelling. The possible influence of conventional glucocorticoid replacement on plasma lipids, plasma LCAT, CETP and PLTP activity levels, as well as on plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) was evaluated in 24 consecutive hypopituitary patients (12 men and 12 women) with untreated growth hormone deficiency of whom 17 had adrenal insufficiency and were treated with cortisone acetate, 25 to 37.5 mg daily. Twenty-three patients were on stable levothyroxin therapy and 22 patients used sex steroids. Urinary excretion of cortisol and cortisone metabolites was higher (p<0.001) in glucocorticoid-treated patients. Body mass index (p<0.08) and fat mass (p<0.12) were not significantly different in patients receiving and not receiving glucocorticoids. Fasting blood glucose, plasma insulin and insulin resistance were similar in the groups. Plasma total (p<0.05) and very low+low density lipoprotein cholesterol (p<0.01) were lower in patients receiving glucocorticoids, whereas HDL cholesterol and plasma triglycerides were not different between patients treated and not treated with glucocorticoids. Plasma LCAT activity was 45% lower (p<0.02) and CETP activity was 34% lower (p<0.05) in patients on glucocorticoid treatment. Multiple regression analysis showed that these effects were independent of gender and fat mass. In glucocorticoid-receiving patients, plasma EST and CET were decreased by 80% (p<0.01) and by 58% (p<0.05), respectively. These changes were at least partly attributable to lower LCAT and CETP activity levels. In contrast, plasma PLTP activity was not different between patients with and without glucocorticoid treatment, suggesting that exogenous glucocorticoids exert a different regulatory effect on plasma CETP compared to PLTP. In conclusion, this preliminary study suggests that conventional glucocorticoid replacement in hypopituitary patients is associated with a decrease in plasma cholesterol esterification and cholesteryl ester transfer, indicating that these steps in HDL metabolism are impaired. Such abnormalities in HDL metabolism could be involved in increased cardiovascular risk in glucocorticoid-treated hypopituitary patients, despite a lack of deterioration in plasma lipids.

Adrenal Insufficiency↗
PubMed2000

Human plasma phospholipid transfer protein increases the antiatherogenic potential of high density lipoproteins in transgenic mice.

Plasma phospholipid transfer protein (PLTP) transfers phospholipids between lipoprotein particles and alters high density lipoprotein (HDL) subfraction patterns in vitro, but its physiological function is poorly understood. Transgenic mice that overexpress human PLTP were generated. Compared with wild-type mice, these mice show a 2.5- to 4.5-fold increase in PLTP activity in plasma. This results in a 30% to 40% decrease of plasma levels of HDL cholesterol. Incubation of plasma from transgenic animals at 37 degrees C reveals a 2- to 3-fold increase in the formation of pre-beta-HDL compared with plasma from wild-type mice. Although pre-beta-HDL is normally a minor subfraction of HDL, it is known to be a very efficient acceptor of peripheral cell cholesterol and a key mediator in reverse cholesterol transport. Further experiments show that plasma from transgenic animals is much more efficient in preventing the accumulation of intracellular cholesterol in macrophages than plasma from wild-type mice, despite lower total HDL concentrations. It is concluded that PLTP can act as an antiatherogenic factor preventing cellular cholesterol overload by generation of pre-beta-HDL.

Animals↗
PubMed2000

Decreasing dietary fat saturation lowers HDL-cholesterol and increases hepatic HDL binding in hamsters.

In order to study the mechanism by which increasing unsaturation of dietary fat lowers HDL-cholesterol levels, we studied various measures of HDL metabolism in hamsters fed with fats with different degrees of saturation. Hamsters were fed on a cholesterol-enriched (1 g/kg) semipurified diet containing 200 g/kg of maize oil, olive oil, or palm oil for 9 weeks. Increasing saturation of dietary fat resulted in increasing concentrations of total plasma cholesterol (4.29 (SD 0.51), 5.30 (SD 0.67) and 5.58 (SD 0.76) mmol/l respectively, n 12) and HDL-cholesterol (3.31 (SD 0.50), 3.91 (SD 0.12) and 3.97 (SD 0.43) mmol/l) and these concentrations were significantly higher (P < 0.05) in the palm-oil and olive-oil-fed hamsters compared with the maize-oil group. Total plasma triacylglycerol levels also increased with increasing fat saturation (1.01 (SD 0.59), 1.56 (SD 0.65) and 2.75 (SD 1.03) mmol/l) and were significantly higher (P < 0.05) in the palm-oil group compared with the olive-oil and maize-oil-fed hamsters. The three diets did not have differential effects on plasma activity levels of lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP). Levels of phospholipid transfer protein (PLTP) tended to be higher with increasing fat saturation but this effect was not significant. The capacity of liver membranes to bind human HDL3 was significantly higher (P < 0.05) in the hamsters fed with maize oil (810 (SD 100) ng HDL3 protein/mg membrane protein, n 4) compared with those fed on palm oil (655 (SD 56) ng/mg), whereas the olive-oil group had intermediate values (674 (SD 26) ng/mg). The affinity of HDL3 for the binding sites was not affected by the type of dietary fat. Hepatic lipase (EC 3.1.1.3) activity, measured in liver homogenates, increased with increasing fat saturation. We conclude that dietary maize oil, when compared with either olive oil or palm-oil, may lower HDL-cholesterol concentrations by enhancing HDL binding to liver membranes.

Animals↗
PubMed2000

Effect of growth hormone replacement therapy on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities in growth hormone-deficient adults.

The effects of growth hormone (GH) replacement on plasma lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP), factors involved in high density lipoprotein (HDL) metabolism, are unknown. We carried out a 6 months study in 24 GH-deficient adults who were randomized to placebo (n = 8), low dose GH (1 U daily, n = 8), and high dose GH (2 U daily, n = 8), followed by a 6 months open extension study with high dose GH (1 drop-out). No significant changes in plasma lipoproteins, LCAT, CETP, and PLTP activities, cholesterol esterification (EST) and cholesteryl ester transfer (CET) were observed after placebo. After 6 months of GH (combined data, n = 24), very low + low density lipoprotein (VLDL + LDL) cholesterol (P < 0.05) and apolipoprotein B (P < 0.05) decreased, whereas HDL cholesterol and HDL cholesteryl ester increased (P < 0. 05). Prolonged treatment showed comparable effects. Plasma apolipoprotein A-I and Lp[a] remained unchanged. Plasma LCAT (P < 0. 01) and CETP activities (P < 0.01), as well as EST (P < 0.01) and CET decreased (P < 0.01) after 12 months of GH (n = 15), but PLTP activity did not significantly change. Changes in EST and CET after 12 months of treatment were independently related to changes in plasma LCAT (P = 0.001 and CETP activity (P = 0.01). In conclusion, GH replacement therapy improves the lipoprotein profile in GH-deficient adults. Chronic GH replacement lowers plasma LCAT and CETP activities, contributing to a decrease in cholesterol esterification and cholesteryl ester transfer. These effects may have consequences for HDL metabolism and reverse cholesterol transport.

Adult↗
PubMed1999

Dietary corn oil versus olive oil enhances HDL protein turnover and lowers HDL cholesterol levels in hamsters.

We studied the effect of dietary olive and corn oil on high-density lipoprotein (HDL) metabolism in golden Syrian hamsters. The animals were fed a semipurified diet containing 0.1% cholesterol and 40 energy % in the form of either olive or corn oil for a period of nine weeks. Hamsters fed corn oil had significantly lower very-low density and low-density lipoprotein (VLDL+LDL) cholesterol concentrations than those fed olive oil (0.98+/-0.24 vs. 1.40+/-0.34 mmol/l, means+/-S.D., n = 12), as well as significantly lower HDL cholesterol concentrations (3.31+/-0.50 vs. 3.91+/-0.12 mmol/l). The binding capacity of 125I-labelled HDL to liver membranes was 33% higher in the hamsters fed corn oil instead of olive oil (571+/-29 vs. 429+/-24 ng HDL protein/mg membrane protein, P<0.05, n = 4). HDL protein kinetics were studied with 125I-HDL using a constant infusion technique. Both HDL fractional catabolic rate (0.255+/-0. 058 vs. 0.121+/-0.023 /h, P<0.01, n = 5) and transport rate (2.386+/-0. 753 vs. 1.218+/-0.101 mg/h, P<0.01, n = 5) were about 2-fold higher in the hamsters fed corn oil. The rate of plasma cholesterol esterification by lecithin: cholesterol acyltransferase (LCAT) was essentially the same for the two diets. It is concluded that the low HDL level in the hamsters fed corn oil diets is linked with increased HDL binding and degradation in the liver and possibly other tissues. Due to increased HDL protein turnover, the capacity for reverse cholesterol transport is increased in hamsters fed corn oil despite the relative low HDL concentrations

Animals↗
PubMed1999

Daily moderate alcohol consumption increases serum paraoxonase activity; a diet-controlled, randomised intervention study in middle-aged men.

Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Part of this inverse association may be explained by its effects on HDL. Paraoxonase, an HDL-associated enzyme, has been suggested to protect against LDL oxidation. We examined the effects of moderate consumption of red wine, beer and spirits in comparison with mineral water on paraoxonase activity in serum. In this diet-controlled, randomised, cross-over study 11 healthy middle-aged men consumed each of the beverages with evening dinner for 3 weeks. At the end of each 3 week period, blood samples were collected pre- and postprandially and after an overnight fast. Fasting paraoxonase activity was higher after intake of wine (P<0. 001), beer (P<0.001), and spirits (P<0.001) than after water consumption (149.4+/-111.1, 152.6+/-113.1, 152.8+/-116.5 and 143. 1+/-107.9 U/l serum), but did not differ significantly between the 3 alcoholic beverages. Similar effects were observed pre- and postprandially. The increases in paraoxonase activity were strongly correlated with coincident increases in concentrations of HDL-C and apo A-I (r=0.60, P<0.05 and r=0.70, P<0.05). These data suggest that increased serum paraoxonase may be one of the biological mechanisms underlying the reduced coronary heart disease risk in moderate alcohol consumers

Adult↗
PubMed1999

A procedure to secure a jugular vein catheter system onto the neck of the hamster.

We describe a procedure to secure a jugular vein catheter system at the dorsal nape of the neck in the hamster. An 8-cm piece of silicone tubing is connected with a 2.6 cm L-shaped metal tubing which is embedded in prosthetic material. The prosthetic material is placed underneath the neck skin of the hamster and keeps the metal end of the catheter system in a sturdy, upright position.

Animals↗
PubMed1999

Plasma phospholipid transfer protein activity is lowered by 24-h insulin and acipimox administration: blunted response to insulin in type 2 diabetic patients.

Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from HDL to VLDL and LDL. Phospholipid transfer protein (PLTP) transfers phospholipids between lipoproteins, converts HDL3 into larger and smaller particles, and is involved in pre-beta-HDL generation. We examined the effects of 24-h hyperinsulinemia (30 mU x kg(-1) x h(-1)) and 24-h Acipimox (250 mg/4 h) on plasma lipids as well as CETP and PLTP activities (measured with exogenous substrate assays) in eight healthy and eight type 2 diabetic subjects. After 24 h of insulin, plasma free fatty acids (FFAs), HDL cholesterol, and plasma apolipoprotein AI decreased in healthy subjects and type 2 diabetic patients (P < 0.05). Plasma triglycerides did not significantly change in either group. After 24 h of Acipimox, all parameters, including plasma triglycerides, decreased in both groups (P < 0.05). Insulin decreased plasma PLTP activity by 17.6% after 24 h in healthy subjects (P < 0.05) and 10.2% in diabetic patients (P < 0.05 vs. baseline; P < 0.05 vs. healthy subjects). Acipimox lowered PLTP activity by 10.3% in healthy subjects (P < 0.05) and 11.3% in diabetic patients (P < 0.05). When insulin was infused for 3 h after Acipimox, a further decrease was found only in healthy subjects. Plasma CETP activity decreased by 9.5% after 24 h of insulin in healthy subjects (P < 0.05), but not in diabetic patients. Acipimox did not decrease plasma CETP activity in either group. In healthy subjects, the PLTP responses with insulin and Acipimox were larger than the changes in CETP activity (P < 0.05). These findings suggest that there is a metabolic link between the regulation of plasma FFA and PLTP, but not CETP. The PLTP response to insulin is blunted in type 2 diabetes.

Adult↗
PubMed1998

Induction of adrenal scavenger receptor BI and increased high density lipoprotein-cholesteryl ether uptake by in vivo inhibition of hepatic lipase.

Hepatic lipase (HL) and scavenger receptor type B class I (SR-BI) have both been implicated in high density lipoprotein (HDL)-cholesteryl ester uptake in cholesterol-utilizing tissues. Inactivation of HL by gene-directed targeting in mice results in up-regulation of SR-BI expression in adrenal gland (Wang, N., Weng, W., Breslow, J. L., and Tall, A. R. (1996) J. Biol. Chem. 271, 21001-21004). The net effect on HDL-cholesteryl ester uptake is not known. We determined the impact of acute in vivo inhibition of rat adrenal HL activity by antibodies on SR-BI expression and on human and rat HDL-[3H]cholesteryl ether (CEth) uptake in the adrenal gland. Rat HDL was isolated from rats in which HL activity had been inhibited for 1 h. The rats were studied under basal conditions (not ACTH-treated) and after previous treatment with ACTH for 6 days (ACTH-treated). Intravenous injection of anti-HL resulted in 70% lowering of adrenal HL activity in both conditions which were maintained for at least 8 h. In not ACTH-treated rats, inhibition of adrenal HL increased adrenal SR-BI mRNA (5.2-fold) and mass (1. 6-fold) within 4 h. HL inhibition resulted in 41% and 14% more adrenal accumulation of human HDL-[3H]CEth during 4 and 24 h, respectively. The adrenal uptake of rat HDL-[3H]CEth increased by 68%, 4 h after the antibody injection. ACTH treatment increased total adrenal HL activity from 3.7 +/- 0.5 milliunits to 34.0 +/- 17. 2 milliunits, as well as adrenal SR-BI mRNA from 2.9 +/- 0.7 arbitrary units (A.U.) to 86.8 +/- 41.1 A.U. and SR-BI mass from 7.7 +/- 1.8 A.U. to 63.16 +/- 46.7 A.U. The human HDL-[3H]CEth uptake by adrenals was also significantly increased from 0.58 +/- 0.11% of injected dose to 7.24 +/- 1.58% of injected dose. Inhibition of adrenal HL activity did not result in further induction of SR-BI expression and did not affect human HDL-[3H]CEth uptake. These findings indicate that SR-BI expression may be influenced by changes in HL activity. HL activity is not needed for the SR-BI-mediated HDL-cholesteryl ester uptake by rat adrenal glands.

Adrenal Glands↗