Cholesterol Journal Articles

Record 3821 to 3840

Cyclooxygenase-2-dependent prostacyclin formation is regulated by low density lipoprotein cholesterol in vitro
Smith, L. H., O. Boutaud, et al. (2002), Arterioscler Thromb Vasc Biol 22(6): 983-8.
Abstract: Reduction of plasma low density lipoprotein (LDL) levels is associated with a reduced risk of myocardial infarction, stroke, and death. Some of this clinical benefit may be derived from an improvement in endothelium-dependent vasodilation. In the present study, we examined the effects of LDL reduction on cyclooxygenase (COX) activity and prostacyclin (PGI2) production. Human umbilical vein endothelial cells exposed to reduced concentrations of LDL demonstrated increased PGI2 production in a dose-dependent manner (from 0.75+/-0.2 to 2.6+/-0.2 ng/mL, P<0.0001). This alteration in PGI2 production did not result from LDL-induced changes in PGI2 synthase expression. However, selective inhibition of COX-2, but not COX-1, blocked PGI2 production under low cholesterol conditions. Addition of exogenous cholesterol induces dose-dependent reductions in endothelial COX-2 expression as measured by reverse transcription-polymerase chain reaction and by Western blotting. Pretreatment of cells with actinomycin D, a transcription inhibitor, reduced COX-2-derived PGI2 production by 45.9% (from 0.55+/-0.09 to 0.25+/-0.08 ng/mL). Taken together, these observations indicate that endothelial PGI2 production is regulated by cholesterol at the transcriptional level and that cholesterol-sensitive transcriptional pathways that regulate COX-2 expression are present in vascular tissue.

Cyclopamine inhibition of Sonic hedgehog signal transduction is not mediated through effects on cholesterol transport
Incardona, J. P., W. Gaffield, et al. (2000), Dev Biol 224(2): 440-52.
Abstract: Cyclopamine is a teratogenic steroidal alkaloid that causes cyclopia by blocking Sonic hedgehog (Shh) signal transduction. We have tested whether this activity of cyclopamine is related to disruption of cellular cholesterol transport and putative secondary effects on the Shh receptor, Patched (Ptc). First, we report that the potent antagonism of Shh signaling by cyclopamine is not a general property of steroidal alkaloids with similar structure. The structural features of steroidal alkaloids previously associated with the induction of holoprosencephaly in whole animals are also associated with inhibition of Shh signaling in vitro. Second, by comparing the effects of cyclopamine on Shh signaling with those of compounds known to block cholesterol transport, we show that the action of cyclopamine cannot be explained by inhibition of intracellular cholesterol transport. However, compounds that block cholesterol transport by affecting the vesicular trafficking of the Niemann-Pick C1 protein (NPC1), which is structurally similar to Ptc, are weak Shh antagonists. Rather than supporting a direct link between cholesterol homeostasis and Shh signaling, our findings suggest that the functions of both NPC1 and Ptc involve a common vesicular transport pathway. Consistent with this model, we find that Ptc and NPC1 colocalize extensively in a vesicular compartment in cotransfected cells.

Cyclosporin A has divergent effects on plasma LDL cholesterol (LDL-C) and lipoprotein(a) Lp(a) levels in renal transplant recipients. Evidence for renal involvement in the maintenance of LDL-C and the elevation of Lp(a) concentrations in hemodialysis patients
Azrolan, N., C. D. Brown, et al. (1994), Arterioscler Thromb 14(9): 1393-8.
Abstract: Cardiovascular disease is the major cause of mortality in renal transplant recipients. Plasma levels of low-density lipoprotein cholesterol (LDL-C) are often elevated following renal transplantation, and the immunosuppressant cyclosporin A has been implicated as a predisposing factor for posttransplantation hyperlipidemia. Lipoprotein(a) Lp(a) is an LDL-like lipoprotein particle; elevated levels of Lp(a) provide an independent and significant risk factor for cardiovascular disease. Plasma concentrations of Lp(a) vary greatly among individuals, and the mechanisms that govern changes in their levels in transplant patients are unknown. The effect(s) of cyclosporin A on Lp(a) was studied in two groups of renal transplantation patients. In group I plasma lipoproteins including Lp(a) were measured before and after successful renal transplantation; this group received both prednisone and cyclosporin A for immunosuppression. Group II patients were studied after renal transplantation and received prednisone alone for immunosuppression. Following surgery, group I patients demonstrated increased plasma concentrations of LDL-C (mean +/- SEM range, 111 +/- 6 to 142 +/- 17 mg/dL; P <.005). In contrast, plasma Lp(a) levels for this group were markedly decreased after renal transplantation (median, 34.3 to 19.7 mg/dL). Patients not treated with cyclosporin A (group II) exhibited mean LDL-C and median Lp(a) levels (118 +/- 42 and 33.1 mg/dL, respectively) that were remarkably similar to those observed before renal transplantation (group I). These data confirm that hyperlipidemia following renal transplantation is associated with cyclosporin A therapy and show that this drug has opposing effects on plasma Lp(a) and LDL-C accumulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporin A inhibits flow-mediated activation of endothelial nitric-oxide synthase by altering cholesterol content in caveolae
Lungu, A. O., Z. G. Jin, et al. (2004), J Biol Chem 279(47): 48794-800.
Abstract: Fluid shear stress generated by blood flowing over the endothelium is a major determinant of arterial tone, vascular remodeling, and atherogenesis. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays an essential role in regulation of vascular function and structure by blood flow. Although cyclosporin A (CsA), an inhibitory ligand of cyclophilin A, is a widely used immunosuppressive drug, it causes arterial hypertension in part by impairing eNOS-dependent vasodilation. Here we show that CsA inhibits fluid shear stress-mediated eNOS activation in endothelial cells via decreasing cholesterol content in caveolae. Exposure of cultured bovine aortic endothelial cells to 1 mum CsA for 1 h significantly inhibited NO production and eNOS phosphorylation at Ser-1179 induced by flow (shear stress=dynes/cm2). The effect of CsA was not related to inhibition of two known eNOS kinases, protein kinase B (Akt) and protein kinase A, because CsA did not affect Akt or protein kinase A activation. In rabbit aorta perfused ex vivo, CsA also significantly inhibited flow-induced eNOS phosphorylation at Ser-1179 but had no effect on Akt measured by phosphorylation at Ser-473. However, CsA treatment decreased cholesterol content in caveolae and displaced eNOS from caveolae, which may be caused by CsA disrupting the association of caveolin-1 and cyclophilin A. The magnitude of the cholesterol depleting effect was similar to that of beta-cyclodextrin, a cholesterol-binding molecule, and beta-cyclodextrin had a similar inhibitory effect on flow-mediated eNOS activation. Treating bovine aortic endothelial cells for 24 h with 30 mug/ml cholesterol blocked the CsA effect and restored eNOS phosphorylation in response to flow. These data suggest that decreasing cholesterol content in caveolae by CsA is a potentially important pathogenic mechanism for CsA-induced endothelial dysfunction and hypertension.

Cyclosporin suppresses transplant arteriosclerosis in the aorta-allografted, cholesterol-clamped rabbit. Suppression preceded by decrease in arterial lipoprotein permeability
Andersen, H. O., G. Madsen, et al. (1994), Arterioscler Thromb 14(6): 944-50.
Abstract: The immunosuppressant cyclosporin has been suggested to aggravate as well as retard the development of transplant arteriosclerosis, the major long-term problem for patients with heart transplants. We examined the effect of human therapeutic levels of blood cyclosporin on the development of experimental transplant arteriosclerosis. The thoracic aorta from one rabbit was transplanted as an end-to-side bypass on the abdominal aorta of another rabbit, and plasma cholesterol was clamped at 5 to 7 mmol/L. Cyclosporin markedly suppressed the severity of transplant arteriosclerosis, judged both biochemically and histologically: cholesterol content in aortic transplants was reduced by 70% and 80% after 10 days and 20 days of cholesterol feeding, respectively (both comparisons, P <.01), and after 20 days of cholesterol feeding myointimal proliferation was totally inhibited in grafts from cyclosporin-treated animals, judged from maximal intimal thickness and intimal area on cross sections of grafts (both comparisons, P <.05). In another group of non-cholesterol-fed, aorta-transplanted rabbits, cyclosporin reduced by 90% (P <.01) an otherwise markedly increased permeability to low-density lipoprotein in transplanted aortas. These results suggest that cyclosporin causes a substantial decrease in the severity of transplant arteriosclerosis and that this effect is mediated at least partly via a large decrease in aortic lipoprotein permeability.

Cyclosporine does not influence serum cholesterol in kidney transplant recipients
Matzkies, F. K., W. Keuthage, et al. (2002), Transplant Proc 34(5): 1795-6.

Cyclosporine treatment reduces early atherosclerosis in the cholesterol-fed rabbit
Drew, A. F. and P. G. Tipping (1995), Atherosclerosis 116(2): 181-9.
Abstract: While T helper cell infiltration is an early event in the development of atherosclerosis in cholesterol-fed rabbits, their functional contribution to atherogenesis is not clear. To investigate their role, T cell activation was blocked with cyclosporine A (CsA) in New Zealand White (NZW) rabbits fed a 1% cholesterol diet. CsA was administered at a dose of 16 mg/kg body weight, intramuscularly every second day, resulting in circulating whole blood levels of 460 +/- 39 micrograms/l. After 4 weeks on the cholesterol diet, untreated rabbits developed atherosclerotic plaques covering 74.4% +/- 3.5% of their aortic arch, 19.8% +/- 7.8% of their thoracic aorta and 19.8% +/- 6.2% of their abdominal aorta. T cells were observed in plaques of their aortic arches (CD5 positive, 11.1 +/- 7.3 cells/mm2; CD4 positive, 9.9 +/- 4.9 cells/mm2) by immunofluorescence using monoclonal anti-rabbit CD5 and CD4 antibodies. Rabbits treated with CsA developed significantly less extensive plaques after 4 weeks (aortic arch 33.0% +/- 6.2%, P < 0.001; thoracic aorta 6.3% +/- 1.5%, P < 0.05; abdominal aorta 2.7% +/- 0.5%, P < 0.005) than untreated rabbits. No CD4 or CD5 positive cells were observed in their plaques. Treatment with CsA did not affect the weight gain of rabbits or reduce their serum cholesterol levels. Circulating T cell numbers and subsets were unaffected. These studies suggest that inhibition of T cell activation prevents their localisation in plaques and reduces the extent of early lesions, suggesting a role for T cells in the initiation of atherosclerosis.

CYP7A1 A-278C polymorphism affects the response of plasma lipids after dietary cholesterol or cafestol interventions in humans
Hofman, M. K., R. M. Weggemans, et al. (2004), J Nutr 134(9): 2200-4.
Abstract: The response of plasma lipids to dietary cholesterol and fat varies among individuals. Variations in genes involved in cholesterol metabolism can be important in these interindividual differences. The rate-limiting enzyme in the conversion of cholesterol into bile acids is cholesterol 7alpha-hydroxylase (CYP7A1). We investigated the effect of the A278-C promoter polymorphism in the CYP7A1 gene on responses of plasma lipids to an increased intake in dietary cholesterol (742 +/- 114 mg/d), cafestol (57 +/- 6 mg/d), saturated fat change of 8-9 energy percent/d (en%/d) and trans fat (change of 10-11 en%/d) in 496 normolipidemic subjects. These responses were measured in 26 previously published dietary trials. After adjustment for the apolipoprotein E genotype effect, AA-subjects consuming a cholesterol-rich diet had a smaller increase in plasma HDL cholesterol than CC-subjects (0.00 +/- 0.02 vs. 0.17 +/- 0.04 mmol/L; P < 0.001). Upon intake of cafestol, AA-subjects had a smaller increase in plasma total cholesterol than CC-subjects (0.69 +/- 0.10 vs. 1.01 +/- 0.10 mmol/L; P = 0.028). No effects of the polymorphism were found in the saturated and trans fat interventions. In conclusion, the CYP7A1 polymorphism has a small but significant effect on the increase in plasma HDL cholesterol and plasma total cholesterol after an increased intake of dietary cholesterol and cafestol, respectively.

Cyproterone acetate could counteract the benefits of estradiol valerate in oophorectomized cholesterol-fed rabbits
Sanjuan, A., C. Castelo-Branco, et al. (2002), Menopause 9(4): 282-7.
Abstract: OBJECTIVE: The administration of hormonal replacement treatment to women with an intact uterus needs to be supplemented with progestogenic compounds to avoid endometrial hyperplasia. However, progestins may cancel the beneficial effects of estrogens on the cardiovascular system. The goal of this study was to examine the effects of adding cyproterone acetate to estradiol (E(2))on aorta atherogenesis. DESIGN: Thirty-two cholesterol-fed New Zealand white rabbits were studied for 4 months. The animals underwent laparotomy and were randomly allocated to four groups. Twenty-four rabbits underwent bilateral ovariectomy, and the other eight were sham-operated (group S). The ovariectomized rabbits were allocated to three groups of eight animals each receiving E(2) valerate (group E), E(2) valerate plus cyproterone acetate (group EC), or placebo after sterilization (group C). RESULTS: After 4 months, the cholesterol-rich diet caused atherosclerotic aortic lesions in both treated groups that affected 17.91% +/- 10.19% and 28.16% +/- 7.97% of the aortic surface of groups E and EC, respectively, with a markedly lower aortic plaque size in group E than in groups C and S. Rabbits from group E (but not from group EC) had aortic cholesterol content significantly lower than rabbits from the sham-operated and control groups. CONCLUSION: E(2) valerate reduces aortic atheromatosis in cholesterol-fed, ovariectomized rabbits, and the addition of cyproterone acetate may neutralize this effect.

Cystic thymoma in a cat with cholesterol-rich fluid and an unusual ultrasonographic appearance
Galloway, P. E., F. J. Barr, et al. (1997), J Small Anim Pract 38(5): 220-4.
Abstract: A cystic thymoma was identified in an eight-year-old domestic longhair cat with a chronic cough. Radiographs indicated a large mass of soft tissue density in the anterior thorax. Ultrasonography revealed an echogenic mass occupying the cranial and mid-thorax with a slight swirling movement of the echoes. Subsequent drainage under ultrasound guidance yielded a cholesterol-rich fluid. The mass was resected at exploratory thoracotomy and the diagnosis of thymoma confirmed. There was no sign of recurrence one year postoperatively. The clinical features and unusual laboratory findings are presented and compared with previously reported cases of thymomata in the cat.

Cytochrome P450 17alpha hydroxylase/17,20 lyase (CYP17) function in cholesterol biosynthesis: identification of squalene monooxygenase (epoxidase) activity associated with CYP17 in Leydig cells
Liu, Y., Z. X. Yao, et al. (2005), Mol Endocrinol 19(7): 1918-31.
Abstract: Cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17) is a microsomal enzyme catalyzing two distinct activities, 17alpha-hydroxylase and 17,20-lyase, essential for the biosynthesis of adrenal and gonadal steroids. CYP17 is a potent oxidant, it is present in liver and nonsteroidogenic tissues, and it has been suggested to have catalytic properties distinct to its function in steroid metabolism. To identify CYP17 functions distinct of its 17alpha-hydroxylase/17,20-lyase activity, we used MA-10 mouse tumor Leydig cells known to be defective in 17alpha-hydroxylase/17,20-lyase activity. A CYP17 knocked down MA-10 clone (MA-10(CYP17KD)) was generated by homologous recombination and its steroidogenic capacity was compared with wild-type cells (MA-10(wt)). Although no differences in cell morphology and proliferation rates were observed between these cells, the human chorionic gonadotropin-induced progesterone formation and de novo synthesis of steroids were dramatically reduced in MA-10(CYP17KD) cells; their steroidogenic ability could be rescued in part by transfecting CYP17 DNA into the cells. Knocking down CYP17 mRNA by RNA interference yielded similar results. However, no significant difference was observed in the steroidogenic ability of cells treated with 22R-hydroxycholesterol, which suggested a defect in cholesterol biosynthesis. Incubation of MA-10(CYP17KD) cells with (14)C-labeled squalene resulted in the formation of reduced amounts of radiolabeled cholesterol compared with MA-10(wt) cells. In addition, treatment of MA-10(CYP17KD) cells with various cholesterol substrates indicated that unlike squalene, addition of squalene epoxide, lanosterol, zymosterol, and desmosterol could rescue the hormone-induced progesterone formation. Further in vitro studies demonstrated that expression of mouse CYP17 in bacteria resulted in the expression of squalene monooxygenase activity. In conclusion, these studies suggest that CYP17, in addition to its 17alpha-hydroxylase/17,20-lyase activity, critical in androgen formation, also expresses a secondary activity, squalene monooxygenase (epoxidase), of a well-established enzyme involved in cholesterol biosynthesis, which may become critical under certain conditions.

Cytochrome P-450 cholesterol side-chain cleavage expression in human spermatozoa
Gunasegaram, R., K. L. Peh, et al. (1998), Horm Metab Res 30(1): 58-60.

Cytochromes P450 in synthesis of steroid hormones, bile acids, vitamin D3 and cholesterol
Pikuleva, I. and M. Waterman (1999), Mol Aspects Med 20(1-2): 33-42, 43-37.

Cytologic diagnosis of cholesterol granuloma. A case report
Heaton, R. B., J. J. Ross, et al. (1993), Acta Cytol 37(5): 713-6.
Abstract: Cholesterol granuloma is a rare lesion of the orbit occurring in adults and must be distinguished from epidermoid cholesteatoma and other mass lesions of the orbit. We report the case of a 31-year-old man who presented to our institution with right eye proptosis secondary to a soft tissue mass. At surgery, cyst fluid from the lesion was sent for cytologic evaluation. The fluid was remarkable for numerous inflammatory cells, blood breakdown products, multinucleate giant cells and cholesterol crystals. The absence of squamous- or respiratory-type epithelium led to a diagnosis of cholesterol granuloma. This was confirmed by histologic examination of the tissue submitted. The differential diagnosis and cytologic features of orbital lesions are discussed.

Cytomegalovirus seropositivity and serum total cholesterol levels in young patients
Froberg, M. K., N. Seacotte, et al. (2001), Ann Clin Lab Sci 31(2): 157-61.
Abstract: Atherosclerosis is a chronic inflammatory disease of arteries, associated with multiple genetic and environmental factors, including hypertension, diabetes mellitus, cigarette smoking, modified and elevated LDL cholesterol, elevated plasma homocysteine, and infectious microorganisms such as Chlamydia pneumoniae and cytomegalovirus (CMV). CMV has been implicated in atherogenesis by epidemiological studies, animal research, and molecular analyses that have demonstrated CMV nucleic acids within human atherosclerotic lesions. Studies have suggested that CMV infection may alter lipid metabolism and lead to accumulation of cholesterol within atheromatous plaques. Few studies have examined the relationship between CMV infection and serum cholesterol levels in younger individuals when much of atherogenesis occurs. To test if CMV-seropositivity is associated with high levels of serum total cholesterol in relatively young patients, CMV IgG levels and total cholesterol concentrations were analyzed in serums from 172 patients, age < 50 yr. Based on univariate analysis of variance, serum total cholesterol was significantly correlated to age and to CMV-seropositivity when gender was a cofactor, but not to gender or CMV-seropositivity alone. In 39 CMV-seropositive women, serum total cholesterol concentration averaged 218 +/- 50 mg/dL (mean +/- SD), which was significantly higher than in 53 CMV-seronegative women (194 +/- 39 mg/dL, p < 0.02). No significant difference was observed between the serum total cholesterol concentrations in 26 CMV-seropositive men and 51 CMV-seronegative men (198 +/- 42 mg/dL versus 212 +/- 48 mg/dl, respectively). Thus, this study provides evidence that CMV-seropositivity is associated with higher serum total cholesterol levels in female patients under 50 yr of age, but not in male patients of comparable age.

Cytoplasmic membrane cholesterol and doxorubicin cytotoxicity in drug-sensitive and multidrug-resistant human ovarian cancer cells
Mazzoni, A. and F. Trave (1993), Oncol Res 5(2): 75-82.
Abstract: The possible involvement of cholesterol (CHOL) in the cellular transformations leading to the acquisition of the multidrug-resistance (MDR) phenotype has been evaluated in human ovarian cancer cells. To this end, the A2780 cell line and the 52-fold doxorubicin (DX)-resistant counterpart A2780-DX3 were analyzed under two different growth conditions: standard culture medium (FCS medium), or medium deprived of CHOL (LPDS medium). The following variables were investigated: free and esterified cytoplasmic membrane CHOL, cell growth, DX uptake and cytotoxicity, and low-density lipoprotein uptake and degradation (as indirect variables of CHOL homeostasis). The impact of the calcium antagonist verapamil (VER) on these variables was assessed. The results obtained indicate that under standard growth conditions, A2780 and A2780-DX3 cells are different not only with respect to DX uptake and sensitivity, but also with respect to membrane CHOL content and the ratio of free-to-esterified CHOL. The deprivation of lipoproteins in the culture medium, apart from slowing cell growth, induced a decrease in the cytoplasmic membrane CHOL content (mainly of the esterified form) that was particularly evident in A2780 sensitive cells. In LPDS medium, a reduced DX uptake occurred in both cell lines, but to a greater extent in A2780 cells, in which DX cytotoxicity decreased to values comparable to that of A2780-DX3 resistant cells. Restoration of DX sensitivity was achieved with the addition of 10 microM VER.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxic cellular cholesterol is selectively removed by apoA-I via ABCA1
Kellner-Weibel, G., S. J. Luke, et al. (2003), Atherosclerosis 171(2): 235-43.
Abstract: Excess intracellular free cholesterol (FC) is cytotoxic. This study examines prevention of FC-induced cytotoxicity in J774 macrophage foam cells by incubation with apolipoprotein AI (apoA-I). J774 were cholesterol enriched using acetylated low-density lipoprotein and FC/phospholipid (PL) dispersions. Treatment with an acyl coenzyme-A:cholesterol acyltransferase (ACAT) inhibitor, in the absence of extracellular acceptors, produced hydrolysis of stored esterified cholesterol (EC) and FC-induced cytotoxicity. Incubation of cells with ACAT inhibitor plus apoA-I resulted in FC efflux (0.39 +/- 0.02%/h) along with a reduction in cytotoxicity (26.30 +/- 5.80%), measured by adenine release. Small unilamellar vesicles (SUV) caused greater FC efflux (0.53 +/- 0.02%/h, P = 0.001), but a modest reduction in cytotoxicity (8.40 +/- 2.70%, P = 0.008). Co-incubation of ACAT inhibitor plus the cholesterol transport inhibitor U18666A or the antioxidant Probucol reduced efflux to apoA-I, but not to SUV. Pre-treatment of J774 foam cells with CTP-cAMP upregulates hormone sensitive lipase (HSL) and further upregulates ATP binding cassette A1 (ABCA1). Using mouse serum as a cholesterol acceptor, CTP-cAMP caused greater protection against FC-induced cytotoxicity compared to cells without pre-treatment, suggesting a role of ABCA1 in removal of cytotoxic FC. We conclude that a cytotoxic pool of FC is located in the plasma membrane, is readily available for efflux to apoA-I, and removal of cytotoxic cholesterol may involve ABCA1.

Cytotoxic cholesterol is generated by the hydrolysis of cytoplasmic cholesteryl ester and transported to the plasma membrane
Kellner-Weibel, G., Y. J. Geng, et al. (1999), Atherosclerosis 146(2): 309-19.
Abstract: The present study examines the fate and effects of free cholesterol (FC) generated by the hydrolysis of cytoplasmic cholesteryl esters (CE) in model macrophage foam cells. J774 or elicited mouse peritoneal macrophages (MPM) were enriched with CE by incubating with acetylated low density lipoprotein (acLDL) and FC/phospholipid dispersions, thus creating model foam cells. Treatment of the foam cells with the acyl coenzyme-A:cholesterol acyltransferase (ACAT) inhibitor, CP-113,818, in the absence of any extracellular cholesterol acceptors, resulted in cellular toxicity. This was accompanied by an increase in the amount of FC available for oxidation by an exogenous cholesterol oxidase. Furthermore, cellular toxicity was proportional to the size of the oxidase susceptible pool of FC over time. Morphological analysis and in situ DNA fragmentation assay demonstrated the occurrence of apoptosis in the ACAT inhibited cells. Co-treatment with the hydrophobic amine U18666A, an intracellular cholesterol transport inhibitor, led to a dose dependent reduction in cytotoxicity and apoptosis, and blocked the movement of FC into the oxidase susceptible pool. In addition, treating model foam cells with CP-113,818 plus chloroquine, a compound that inhibits the function of acidic vesicles, also diminished cellular toxicity. Staining with the cholesterol binding dye filipin revealed that the macrophages treated with CP-113,818 contained a cholesterol oxidase accessible pool of FC in the plasma membrane. These results suggest that FC generated by the hydrolysis of cytoplasmic CE is transported through acidic vesicles to the plasma membrane, and accumulation of FC in this pool triggers cell death by necrosis and apoptosis.

Cytotoxicity and suppression of immunoglobulin production against human Namalwa cells caused by oxidized cholesterol
Osada, K., T. Kodama, et al. (1996), Biosci Biotechnol Biochem 60(8): 1362-4.
Abstract: The effects of oxidized cholesterols on proliferation and IgM production of human lymphoblastoid Namalwa cells were examined. An oxidized cholesterol mixture, in contrast to cholesterol, was a potent cytotoxin to Namalwa cells. Among oxidized cholesterols examined, 25-hydroxycholesterol was the most cytotoxic. However, no oxidized cholesterol examined suppressed IgM production, although cholestanetriol and 7-ketocholesterol did suppress it. Thus, oxidized cholesterols are cytotoxic to lymphocytes, while the influence on the immunoglobulin production may be marginal.

Daily intakes of fatty acids, sterols, and phospholipids by Japanese women and serum cholesterol
Ishinaga, M., S. Sugiyama, et al. (1994), J Nutr Sci Vitaminol (Tokyo) 40(6): 557-67.
Abstract: The daily intakes of various lipids by 72 Japanese women (40-59 years of age) were measured directly from mock samples of food actually consumed (this method is similar to the duplicate portion method). One sample was collected from each of 12 subjects every 2-months for a period of 1 year. The daily intakes of total fatty acid (FA), cholesterol, plant sterol, phospholipid (PL), and phosphatidylcholine (PC) were 37.9 g, 300 mg, 152 mg, 3.1 g, and 1.7 g, respectively. No effect of the sampling period was found for any lipid measured. The combined eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids showed marked individual variation, and ranged from 0 to 4.3 g, and the average was 0.8 g. The n6/n3 polyunsaturated fatty acids (PUFA) ratio ranged from 0.9 to 19.1 (average, 4.2). There was a strong correlation only between cholesterol and PL intakes (r = 0.796, p < 0.05). The mean serum cholesterol, which was known in 42 subjects was 190 mg/dl, and showed no relation to their daily intakes of any of the measured lipids.

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