Cholesterol Journal Articles

Record 4941 to 4960

Effect of hyperpnea on the cholesterol to disaturated phospholipid ratio in alveolar surfactant of rats
Orgeig, S., H. A. Barr, et al. (1995), Exp Lung Res 21(1): 157-74.
Abstract: Hyperpnea induced by swimming rats for 30 min decreased the cholesterol/disaturated phospholipid ratio (CHOL/DSP) in the tubular myelin-poor fraction (alv-2), but did not affect the tubular myelin-rich fraction (alv-1). The phenomenon was further illustrated by the marked inverse relationship between CHOL/DSP and DSP. Because such a result could reflect differential release, processing, or reuptake within the alveolar compartment, this study further explored the mechanism in the rat isolated perfused lung (IPL), using radiolabeled CHOL (3H) and DSP (14C). The study also examined whether the decrease in CHOL/DSP with swimming was associated with the increase in either tidal volume (VT), frequency of breathing (f), or both. It was found that whereas a 2.5-fold increase in VT for 15 min in the IPL increased the CHOL/DSP in alv-1 and decreased it in alv-2, a 3-fold increase in f markedly increased the CHOL/DSP in both alveolar subfractions. In apparent contrast, the increases in both VT and f markedly depressed the ratio of the sp act of CHOL/DSP, reflecting a large decrease in the sp act of CHOL in the alveolar compartment. In view of the acute nature of these IPL experiments, it is suggested that the changes reflect the differential release of CHOL and DSP. Furthermore, the marked decrease in sp act of CHOL must reflect a second source of CHOL supplying the alveolar compartment with sterol of low sp act. It is concluded that there is differential handling of surfactant CHOL and DSP in the alveolar compartment of the rat and that the decrease in CHOL/DSP with swimming is due to an increase in VT.

Effect of hypocholesterolemic doses of 17 alpha-ethinyl estradiol on cholesterol balance in liver and extrahepatic tissues
Bertolotti, M. and D. K. Spady (1996), J Lipid Res 37(8): 1812-22.
Abstract: This study was performed to investigate the effects of 17 alpha-ethinyl estradiol, a potent hypocholesterolemic agent at pharmacological doses, on cholesterol balance in the liver and extrahepatic tissues of the rat in vivo. Female Sprague-Dawley rats were treated with 17 alpha-ethinyl estradiol (5 mg/kg per day s.c. for 5 days) or with 4-aminopyrazolo(3,4-d) pyrimidine (20 mg/kg per day i.p. for 3 days). Both drug regimens suppressed plasma total and low density lipoprotein-cholesterol by more than 80%. Analysis of the kinetic parameters of low density lipoprotein transport did not show increased receptor activity in extrahepatic tissues during either treatment. 17 alpha-Ethinyl estradiol significantly increased low density lipoprotein tissue spaces and clearance rates in the liver, with a 5-fold increase in low density lipoprotein-receptor activity, whereas 4-aminopyrazolo(3,4-d)pyrimidine suppressed hepatic transport of low density lipoprotein probably due to a nospecific toxic effect. Treatment with 17 alpha-ethinyl estradiol markedly enhanced the hepatic expression of low density lipoprotein-receptor protein and mRNA despite a 7-fold increase in hepatic cholesteryl ester levels. Finally, treatment with both drugs increased cholesterol synthesis in several extrahepatic tissues, such as adrenals, ovaries, small bowel, and spleen. These findings confirm that 17 alpha-ethinyl estradiol at pharmacological doses markedly increases synthesis and expression of low density lipoprotein-receptor in the liver. Hypocholesterolemia, whether induced by activation of low density lipoprotein-receptors or by other mechanisms, fails to up-regulate low density lipoprotein transport in extrahepatic tissues, which rather respond by increasing local sterol synthesis. This suggests the occurrence of separate regulatory mechanisms for low density lipoprotein transport and cholesterol synthesis.

Effect of ileal autotransplantation on cholesterol, bile acids, and biliary lipids in pigs with proximal small bowel resection
Pakarinen, M., T. A. Miettinen, et al. (1997), Hepatology 25(6): 1315-22.
Abstract: Our major aim was to investigate the consequences of ileal autotransplantation in pigs with proximal small intestinal resection on biliary lipids and metabolism of bile acids. Biliary lipid secretion rates and bile acid absorption were assessed by measuring dietary and biliary lipids, fractional cholesterol absorption, and fecal excretion of cholesterol and bile acids. In addition, serum bile acids and cholesterol, biliary and fecal bile acid species, and ileal villus height were determined after resection of the proximal 75% of the jejunoileum (n = 15) and autotransplantation of the remaining ileum with systemic venous drainage (n = 15) or transection (n = 5). Autotransplantation further increased fecal excretion of neutral and acidic steroids and serum concentration of bile acids after proximal resection (P <.05 for all); autotransplantation significantly decreased serum cholesterol, ileal villus height, fractional bile acid and cholesterol absorption, and biliary molar percentage of total and primary bile acids, whereas biliary secretion of bile acids, enriched by secondary bile acids, and cholesterol remained unchanged. At 14 weeks, ileal villus height, fractional bile acid and cholesterol absorption, biliary molar percentage of bile acids, and proportion of secondary biliary bile acids were altered by transplantation from the respective postresection values of 864 +/- 22 microm, 97.9 +/- 0.6%, 26.9 +/- 3.9%, 91.8 +/- 1.2% and 9.2 +/- 1.3% to 428 +/- 21 microm, 91.1 +/- 1.5%, 9.5 +/- 1.1%, 83.9 +/- 1.4% and 52.5 +/- 3.5% (P <.005 for all). Posttransplantation biliary bile acid secretion correlated positively with fractional reabsorption (r =.70) and biliary molar percentage (r =.73) of bile acids and ileal villus height (r =.65; P <.01 for all). Decreased absorption efficiency and biliary molar percentage of bile acids, increased biliary secondary bile acids, and short ileal villi point to bacterial overgrowth-induced bile acid malabsorption, which with decreased absorptive area may contribute to malabsorption of other lipids after ileal autotransplantation. Compensatory increase in cholesterol synthesis in the pigs with autotransplanted ileum appeared sufficient for constant biliary secretion of cholesterol and bile acids.

Effect of increased depletion of copper, supplementary cholesterol diet and stress on the cholesterol concentration in wall of rat thoracic aorta
Toth, E. and P. Remes (1994), Acta Physiol Hung 82(2): 125-30.
Abstract: The effects of experimental copper deficiency by itself, and in combination with other factor resulting in ischaemic heart diseases (IHD), were investigated on the lipid composition and copper status of serum and aortic wall in rat. The depletion of absorbed copper was raised by complex formation (D-penicillamine-treatment). This provoked secondary copper deficiency was combined with a dietary cholesterol- and stress-loading. After treatment the levels of triglyceride (Tg), total cholesterol (Chol), HDL-cholesterol (HDL) (HDL = high density lipoprotein) and HDL2-cholesterol (HDL2) as well as copper (Cu) and zinc (Zn) in the serum and in aortic wall were measured by chemical analysis. It was pointed out, that increase in triglyceride and total cholesterol levels were promoted by the provoked copper deficiency in the serum and in the wall of the thoracic aorta. In combination with other risk factors it caused an increase in the elevation of Tg and Chol concentrations and has reduced the level of HDL2, significantly.

Effect of increasing the expression of cholesterol transporters (StAR, MLN64, and SCP-2) on bile acid synthesis
Ren, S., P. Hylemon, et al. (2004), J Lipid Res 45(11): 2123-31.
Abstract: There are two major pathways of bile acid synthesis: the "neutral" pathway, initiated by highly regulated microsomal cholesterol 7alpha-hydroxylase (CYP7A1), and an "alternative" pathway, initiated by mitochondrial sterol 27-hydroxylase (CYP27A1). In hepatocyte cultures, overexpression of CYP7A1 increases bile acid synthesis by >8-fold. However, overexpression of CYP27A1 in hepatocytes only increases it by 1.5-fold, suggesting that additional rate-limiting steps must be involved in the regulation of this pathway. The effects of intracellular cholesterol transport proteins on bile acid synthesis have been investigated in the current study. Under culture conditions in which the neutral pathway was inactive, selective overexpression of the gene encoding steroidogenic acute regulatory protein (StAR), MLN64 (StAR homolog protein), and sterol carrier protein-2 (SCP-2) led to 5.7-, 1.2-, and 1.7-fold increases, respectively, in the rates of bile acid synthesis in primary rat hepatocytes. Surprisingly, co-overexpression of MLN64 with StAR, SCP-2, or CYP7A1 blunted the upregulated bile acid synthesis by 48, 47, and 45%, respectively. These results suggest that MLN64, in its full-length form, is not responsible for the transport of cholesterol to the mitochondria or the endoplasmic reticulum, where CYP27A1 or CYP7A1 is located, respectively.

Effect of inflammatory attacks in the classical type hyper-IgD syndrome on immunoglobulin D, cholesterol and parameters of the acute phase response
Simon, A., J. Bijzet, et al. (2004), J Intern Med 256(3): 247-53.
Abstract: BACKGROUND: Classical type hyper-immunoglobulin D (IgD) syndrome (HIDS) is an hereditary auto-inflammatory disorder, characterized by recurrent episodes of fever, lymphadenopathy, abdominal distress and a high serum concentration of IgD. It is caused by mevalonate kinase deficiency. OBJECTIVE: To further characterize the acute phase response during fever attacks in HIDS in order to improve diagnosis. SUBJECTS: Twenty-two mevalonate kinase-deficient HIDS patients. METHODS: Blood samples were drawn during and in between febrile attacks, and concentrations ofC-reactive protein (CRP), ferritin, procalcitonin, pentraxin 3, IgD and cholesterol in several lipoprotein fractions were determined. RESULTS: The marked acute phase response at the time of a fever attack in classical type HIDS is reflected by a rise in CRP accompanied by a moderate but statistically significant rise in procalcitonin and pentraxin 3. In only two of 22 patients, procalcitonin concentration rose above 2 ng mL(-1) during fever attack, compatible with the noninfectious nature of these attacks. Ferritin does not reach the high concentrations found in adult-onset Still's disease. Despite the defect in mevalonate kinase, a component of cholesterol metabolism, serum cholesterol did not change during attacks. IgD concentration is elevated regardless of disease activity, although there is appreciable variation during life. Its role in HIDS remains unclear. CONCLUSION: The combination of high CRP concentration plus procalcitonin concentration <2 ng mL(-1) in a symptomatic HIDS patient might indicate a febrile attack without (bacterial) infection; this observation warrants further investigation for its usefulness as a marker in clinical practice.

Effect of ingestion of raw garlic on serum cholesterol level, clotting time and fibrinolytic activity in normal subjects
Gadkari, J. V. and V. D. Joshi (1991), J Postgrad Med 37(3): 128-31.
Abstract: The effect of raw garlic on serum cholesterol, fibrinolytic activity and clotting time was studied in 50 medical students of the age group of 17 to 22 years before and after feeding raw garlic. All pre-experimental values ranged within normal limits. The volunteers were then divided into experimental and control groups. The subjects of the experimental group were given 10 gm of raw garlic daily after breakfast for two months. Fasting blood samples of all the subjects were investigated after two months. In the control group, there was no significant change in any of the above parameters. In the experimental group, there was a significant decrease in serum cholesterol and an increase in clotting time and fibrinolytic activity. Hence, garlic may be an useful agent in prevention of thromboembolic phenomenon.

Effect of inhibition of cholesterol synthetic pathway on the activation of Ras and MAP kinase in mesangial cells
Bassa, B. V., D. D. Roh, et al. (1999), Biochim Biophys Acta 1449(2): 137-49.
Abstract: Intermediary metabolites of cholesterol synthetic pathway are involved in cell proliferation. Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, blocks mevalonate synthesis, and has been shown to inhibit mesangial cell proliferation associated with diverse glomerular diseases. Since inhibition of farnesylation and plasma membrane anchorage of the Ras proteins is one suggested mechanism by which lovastatin prevents cellular proliferation, we investigated the effect of lovastatin and key mevalonate metabolites on the activation of mitogen-activated protein kinase (MAP kinase) and Ras in murine glomerular mesangial cells. The preincubation of mesangial cells with lovastatin inhibited the activation of MAP kinase stimulated by either FBS, PDGF, or EGF. Mevalonic acid and farnesyl-pyrophosphate, but not cholesterol or LDL, significantly prevented lovastatin-induced inhibition of agonist-stimulated MAP kinase. Lovastatin inhibited agonist-induced activation of Ras, and mevalonic acid and farnesylpyrophosphate antagonized this effect. Parallel to the MAP kinase and Ras data, lovastatin suppressed cell growth stimulated by serum, and mevalonic acid and farnesylpyrophosphate prevented lovastatin-mediated inhibition of cellular growth. These results suggest that lovastatin, by inhibiting the synthesis of farnesol, a key isoprenoid metabolite of mevalonate, modulates Ras-mediated cell signaling events associated with mesangial cell proliferation.

Effect of insulin-like growth factor-I on cholesterol side-chain cleavage cytochrome P450 messenger ribonucleic acid expression in ovarian theca-interstitial cells stimulated to differentiate in vitro
Magoffin, D. A. and S. R. Weitsman (1993), Mol Cell Endocrinol 96(1-2): 45-51.
Abstract: Currently available evidence supports the hypothesis that insulin-like growth factor-I (IGF-I) may play a role in stimulating ovarian theca-interstitial cell (TIC) differentiation in preantral follicles. The purpose of the present studies was to examine the potential role of IGF-I in TIC differentiation by determining the effects of IGF-I on cholesterol side-chain cleavage cytochrome P450 (P450SCC) mRNA expression in TIC stimulated to differentiate in vitro. TIC were isolated from the ovaries of hypophysectomized immature rats by Percoll gradient centrifugation and cultured in the presence and absence of LH and IGF-I up to 6 days. At various times cytoplasmic RNA was extracted from the TIC and P450SCC mRNA was measured by specific assay using reverse transcription followed by the polymerase chain reaction. Increasing concentrations of LH (0-1 microgram/ml) stimulated a dose-related increase in P450SCC mRNA (ED50 = 36.2 +/- 5.5 ng/ml) which reached maximal levels at 100 ng/ml of LH. Addition of IGF-I (30 ng/ml) caused a small increase in P450SCC mRNA over TIC treated with LH alone but did not alter the ED50 for LH stimulation. IGF-I alone also stimulated an increase in P450SCC mRNA which reached approximately 3-fold over unstimulated levels at 100 ng/ml. In the presence of LH, IGF-I stimulated a dose-related increase in P450SCC mRNA (ED50 = 1.2 +/- 0.05 ng/ml). Time-course studies revealed that expression of P450SCC mRNA was greatest at 2 days in TIC treated with IGF-I alone, LH alone or LH plus IGF-I and then declined at 4 and 6 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of interleukin-3 on lipoprotein(a) and lipoprotein cholesterol levels
Masse, J. (1995), Am J Cardiol 76(10): 747.

Effect of intralipid infusion on serum high- and low-density lipoprotein cholesterol, lecithin:cholesterol acyltransferase, and lipoprotein lipase in tumor-bearing rats
Wasan, K. M. and V. B. Grossie, Jr. (1995), Experientia 51(3): 230-4.
Abstract: We compared the effects of 0.45% normal saline (NS), 5% Intralipid (IL), and 16.7% glucose (Glu) infusions on total serum triglycerides and cholesterol, serum high-(HDL-c) and low-density lipoprotein cholesterol (LDL-c), and activity of serum lecithin:cholesterol acyltransferase (LCAT), and serum lipoprotein lipase (LPL) in rats implanted with a fibrosarcoma. In tumor-bearing rats given NS, a two-fold increase in total serum cholesterol, a four-fold increase in LDL-c, and a five-fold decrease in the HDL-c/LDL-c ratio were observed compared to tumor-free rats. In tumor-bearing rats administered IL, a two-fold increase in total serum triglyceride and cholesterol, a three-fold increase in HDL-c and HDL-c/LDL-c ratio, and a two-fold increase in LPL activity were observed compared to tumor-bearing rats administered NS. In tumor-bearing rats administered Glu, a two-fold decrease in total serum cholesterol, a two-fold decrease in HDL-c, and a three-fold decrease in LDL-c were observed compared to tumor-bearing rats administered NS. Tumor weights and LCAT activity did not differ significantly between treatment groups. Previous results have demonstrated that lipophilic compounds that interact with plasma lipoproteins have altered pharmacological effects when administered with IL. Therefore, this study suggests that IL infusions alter the HDL-c/LDL-c ratio and could affect the pharmacological behavior of anticancer compounds that predominantly distribute into the LDL fraction upon entrance into the bloodstream.

Effect of intravenous lipid emulsions on hepatic cholesterol metabolism
Whitfield, P. D., P. T. Clayton, et al. (2000), J Pediatr Gastroenterol Nutr 30(5): 538-46.
Abstract: BACKGROUND: Total parenteral nutrition offers the chance of survival to children who have had extensive gut resections or gut failure. However, in infants it is often associated with serious complications including cholestatic liver disease. The causes of these complications remain unclear, although it has been suggested that the lipid emulsions used in total parenteral nutrition may be responsible. METHODS: An in vitro system was developed to study the effect of lipid emulsions on hepatic cholesterol metabolism using cultured hepatocytes. RESULTS: Incubations of Hep G2 cells with medium containing Intralipid (Pharmacia and Upjohn, Milton Keynes, UK) demonstrated that the fat emulsion mediated a powerful dose-dependent but reversible inhibition of cholesterol uptake. In addition Intralipid was shown to stimulate the efflux of cholesterol from Hep G2 cells. The component or components of the Intralipid responsible for these effects and the mechanism by which they act remain to be established. CONCLUSIONS: Intravenous lipid emulsions may interfere with hepatic cholesterol metabolism in vivo. This may have implications for the development of total parenteral nutrition-associated cholestasis in neonates.

Effect of isradipine on the formation and regression of fatty streaks in cholesterol fed rabbits
Kunjara-Na-Ayudhya, R., A. B. Thomson, et al. (1994), Cardiovasc Res 28(7): 1089-95.
Abstract: OBJECTIVE: The aim was to determine whether the antiatherogenic effect of the calcium channel blocker isradipine on fatty streak formation was dependent upon a temporal relationship between cholesterol feeding and administration of the drug. METHODS: The study was done in New Zealand White rabbits fed a diet supplemented with cholesterol (2.5% w/w) for three weeks. Such a regimen results in loss of endothelium dependent relaxation and accumulation of cholesterol in the aorta four weeks later. The calcium antagonist isradipine was given in a dose of 0.25 mg.kg-1.d-1 at specified periods during the study to seven subgroups of animals: (1) standard diet + 2.5% cholesterol for three weeks; (2) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks; (3) standard diet + 2.5% cholesterol for three weeks followed by standard diet for 12 weeks; (4) standard diet + 2.5% cholesterol+isradipine for three weeks followed by standard diet alone for four weeks; (5) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks with isradipine given throughout the seven weeks; (6) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks with isradipine given during the final four weeks only; (7) standard diet + 2.5% cholesterol for three weeks followed by standard diet for 12 weeks with isradipine given during the final eight weeks. Aortic tissue was removed for measurement of cholesterol content, endothelium dependent relaxation to acetylcholine and the calcium ionophore A23187, and relaxant responses to sodium nitrite. Serum was collected for measurement of cholesterol and triglyceride concentration. RESULTS: When isradipine was given either during cholesterol feeding and continued for four weeks following it (subgroup 5) or during the four weeks following cholesterol feeding (subgroup 6), loss of endothelium dependent relaxation and the accumulation of cholesterol in the aorta was prevented. However, administration of isradipine during the period of cholesterol feeding alone (subgroup 4) was without effect. Also, administration of isradipine after lesions of fatty acid streak type were established appeared to have a favourable effect on removal of cholesterol from the aorta. CONCLUSIONS: Isradipine protects against the development of fatty streaks in rabbits fed a diet supplemented with 2.5% cholesterol. Administration of this drug after fatty streaks are formed also promotes their resolution.

Effect of jiang-zhi zhong-yao-pian on total cholesterol, triglyceride, TXB2, 6-keto-PGF1 alpha in hyperlipemic patients
Liang, X. C. and S. S. Guo (1991), Zhong Xi Yi Jie He Za Zhi 11(1): 20-2, 4.
Abstract: The purpose of this study was to verify the effect of a Chinese herbal medicine Jiang-Zhi Zhong-Yao-Pian to reduce serum lipoid. Efficacy was observed in 30 cases of hyperlipemia; 20 cases administered with evening primose oil capsules were taken as controls. Each group took drugs for two or three months. The results were as follows: After treatment as compared with before treatment, the serum levels of TC, TG and TXB2 dropped from 264.28 +/- 70.52 mg%, 393.52 +/- 250.42 mg% and 110.75 +/- 43.52 pg/ml to 225.60 +/- 50.93 mg%, 264.97 +/- 252.81 mg% and 88.82 +/- 46.50 pg/ml respectively (P less than 0.001, less than 0.01, less than 0.05). However, in the group taking evening primrose oil capsules, TC, TG and TXB2 in comparing with the pre-treatment levels were changed from 251.33 +/- 58.24 mg%, 316.35 +/- 104.93 mg% and 131.53 +/- 49.77 pg/ml to 244.30 +/- 43.28 mg%, 272.10 +/- 92.52 mg% and 115.33 +/- 47.49 pg/ml respectively (P greater than 0.05, less than 0.05, greater than 0.05). This medicine had no side-effect. The results showed that the herbal formula might be useful to reduce serum TC, TG and TXB2.

Effect of ketoconazole on the activity of key enzymes of biosynthesis of cholesterol and its esters in the liver of rats maintained on a cholesterol-enriched diet
Dushkin, M. I. and M. V. Ivanova (1992), Ukr Biokhim Zh 64(3): 73-6.
Abstract: Ketoconazole in vivo has been studied for its effect on the activity of key enzymes of the cholesterol and its esters' biosynthesis in the liver and on the cholesterol concentration in certain fractions of blood lipoproteins in normal and cholesterol-fed rats. It is established that ketoconazole decreases cholesterol concentration in low-density lipoproteins and in very low-density lipoproteins as well as decrease the acyl-CoA-cholesterol acyl-transferase activity and increases the 3-hydroxy-3-methyl-glutaryl-CoA-reductase activity in the liver microsomes of intact and test animals. It is supposed that the possible cause of the observed changes can be a disturbance in regulation of basic links of cholesterol metabolism in the liver.

Effect of labeling of plasma lipoproteins with (3)Hcholesterol on values of esterification rate of cholesterol in apolipoprotein B-depleted plasma
Dobiasova, M., L. Adler, et al. (2000), J Lipid Res 41(8): 1356-7.
Abstract: The fractional esterification rate of cholesterol in apolipoprotein B (apoB)-depleted plasma (FER(HDL)) is a good indicator of particle size distribution in high density lipoprotein (HDL) and low density lipoprotein (LDL). However, there has been a discrepancy in the absolute values of FER(HDL) published by different laboratories. Because the main difference between the methods was in the labeling of lipoproteins with (3)Hcholesterol we investigated the effect of using Corning immunoplates and paper discs as carriers of the labeled unesterified cholesterol. We found that Corning plates trap some (3)H-labeled free cholesterol, which is released during incubation at 37 degrees C. This means that this additional (3)H-labeled free cholesterol is exposed to lecithin: cholesterol acyltransferase (LCAT) for a shorter time and artificially decreases FER(HDL). Using paper discs discarded before incubation as carriers of the (3)H-labeled free cholesterol results in complete labeling of HDL and thus yields higher values of FER(HDL).

Effect of lacidipine on cholesterol esterification: in vivo and in vitro studies
Bernini, F., M. Canavesi, et al. (1997), Br J Pharmacol 122(6): 1209-15.
Abstract: 1. Cholesterol esterification and accumulation in the arterial wall is a hallmark of atherogenesis. Several preclinical studies suggest that calcium antagonists may exert antiatherosclerotic activity by directly affecting atherogenesis in the arterial wall. We investigated the effect of the second generation dihydropyridine calcium antagonist lacidipine on cholesterol metabolism in vivo in the aortic arch of cholesterol fed rabbits, and in vitro in mouse cultured peritoneal macrophages. 2. Treatment of cholesterol-fed rabbits with 1, 3 and 10 mg kg-1 day-1 of lacidipine for two months reduced, in a dose-dependent manner, cholesterol esterification in the aortic arch: 24 +/- 6, 30 +/- 12, and 41 +/- 8% inhibition, respectively (P < 0.001 vs HC control). Concomitantly, drug treatment reduced total cholesterol content of the vessel wall. Lacidipine 3 and 10 mg kg-1 day-1 reduced cholesterolaemia (approximately 20%); no effect was observed at the lowest dose used (1 mg kg-1 day-1). These results suggest that the action of lacidipine on cholesterol esterification in the arterial wall involves, at least in part, a direct effect on cellular cholesterol metabolism. Inhibition of cholesterol esterification in the arterial wall was observed also in a reference group of animals treated with the specific ACAT inhibitor CI-976. 3. To evaluate the action of lacidipine on intracellular cholesterol metabolism we performed in vitro experiments with murine macrophages, the main cell type that accumulates cholesterol in the arterial wall. Lacidipine almost completely inhibited cholesterol esterification in cholesterol loaded macrophages in culture. The effect was observed independently of esterification stimuli and in cell free homogenates. The drug modified intracellular cholesterol distribution, doubling the free- to esterified sterol ratio, but did not influence the cellular rate of cholesteryl ester hydrolysis in the cell. All together these results indicate an inhibitory effect of lacidipine on cholesterol esterification catalyzed by the enzyme ACAT in murine macrophages. 4. We concluded that lacidipine influences cellular cholesterol metabolism. This effect may contribute to the potential antiatherosclerotic activity of this drug.

Effect of laser fragmentation of cholesterol and mixed gallstones on in vitro dissolution in methyl tert-butyl ether
Smith, B. F. (1990), Dig Dis Sci 35(2): 236-41.
Abstract: This study examined cholesterol and mixed gallstone dissolution in vitro by methyl-tert-butyl ether (MTBE) after gallstone fragmentation. Three morphologically identical gallstones were obtained from 42 patients. One stone from each patient was fragmented with laser energy at a wavelength of 504 nm delivered to the stone surface with a 320-microns quartz fiber. Intact and fragmented stones from the same patient were incubated without stirring in MTBE and dissolution was expressed as the percent of initial stone weight remaining after 2 hr. Stone composition did not correlate with the amount of laser energy required for stone fragmentation. Fragmented stones dissolved faster than intact stones in MTBE with 13.97% +/- 0.37% vs 31.0% +/- 0.51% respectively (mean +/- SEM) of initial stone weight remaining at 2 hr (P less than 0.0001). Initial stone weight and stone matrix content significantly predicted dissolution of intact (P = 0.0033 and P = 0.0483, respectively) and fragmented stones (P = 0.003 and P = 0.0001, respectively) in MTBE. These data suggest that the gallstone matrix may inhibit stone dissolution even after stone fragmentation.

Effect of LCAT on HDL-mediated cholesterol efflux from loaded EA.hy 926 cells
Kilsdonk, E. P., A. N. Dorsman, et al. (1993), Int J Biochem 25(2): 219-21.
Abstract: 1. Human endothelial cells (EA.hy 926 line) were loaded with cholesterol, using cationized LDL, and the effect of lecithin:cholesterol acyltransferase (LCAT) on cellular cholesterol efflux mediated by high density lipoproteins (HDL) was measured subsequently. 2. In plasma, lecithin:cholesterol acyltransferase (LCAT) converts unesterified HDL cholesterol into cholesteryl esters, thereby maintaining the low UC/PL ratio of HDL. It was tested if further decrease in UC/PL ratio of HDL by LCAT influences cellular cholesterol efflux in vitro. 3. Efflux was measured as the decrease of cellular cholesterol after 24 hr of incubation with various concentrations of HDL in the presence and absence of LCAT. LCAT from human plasma (about 3000-fold purified) was added to the cell culture, resulting in activity levels in the culture media of 60-70% of human serum. 4. Although LCAT had a profound effect on HDL structure (UC/TC and UC/PL ratio's decreased), the enzyme did not enhance efflux of cellular cholesterol, using a wide range of HDL concentrations (0.05-2.00 mg HDL protein/ml). 5. The data indicate that the extremely low unesterified cholesterol content of HDL, induced by LCAT, does not enhance efflux of cholesterol from loaded EA.hy 926 cells. It is concluded that the HDL composition (as isolated from plasma by ultracentrifugation) is optimal for uptake of cellular cholesterol.

Effect of LDL+VLDL oxidizability and hyperglycemia on blood cholesterol, phospholipid and triglyceride levels in type-I diabetic patients
Jain, S. K., R. McVie, et al. (2000), Atherosclerosis 149(1): 69-73.
Abstract: Oxidative modification of low-density lipoproteins has been implicated in impaired lipid metabolism and its deposition in the arterial wall, and atherosclerosis. This study was carried out to determine the relationship between the in vitro oxidizability of low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) and the cholesterol, phospholipid and triglyceride (TG) levels in the blood of Type-I diabetic patients. LDL+VLDL was isolated using a micro-affinity column from serum of diabetic patients (n = 34) and age-matched normal individuals (n = 22). The oxidative susceptibility of LDL+VLDL was determined by treatment with 25 microM CuCl(2) for 1.5 h. The levels of total-, LDL-, and HDL-cholesterol, phospholipids and triglycerides, as well as glycated hemoglobin (HbA(t)), were measured in the blood using standard methods. The diabetics had significantly higher levels of triglycerides and phospholipids, but cholesterol levels were similar between Type-I diabetics and age-matched normals. However, among diabetics, there was a significant correlation between the in vitro oxidation of LDL+VLDL at 1.5 h and total cholesterol (r = 0.49, P<0.002), and LDL cholesterol (r = 0.54, P<0.001) and TG (r = 0.34, P<0.05) levels. The level of in vitro oxidizability of LDL+VLDL did not have any correlation with HDL-cholesterol or phospholipid levels. The level of glycemic control (HbA(1)) did not have any correlation with levels of LDL- or HDL-cholesterol or triglycerides, but was significantly correlated with phospholipid levels (r = 0.48, P<0.005). This study suggests that the levels of LDL-cholesterol and triglycerides in the blood are directly related to the degree of in vitro oxidative susceptibility of low-density lipoproteins in Type-1 diabetic patients.

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