Cholesterol Journal Articles

Record 1981 to 2000

Cholesterol and phosphoinositides increase affinity of the epidermal growth factor receptor
den Hartigh, J. C., P. M. van Bergen en Henegouwen, et al. (1993), Biochim Biophys Acta 1148(2): 249-56.
Abstract: The epidermal growth factor receptor (EGF-R) has been purified from human epidermoid carcinoma A431 cells by affinity chromatography in a single step using a monoclonal antibody (528) which competes with EGF for receptor binding. The purified EGF-R exhibits EGF inducible tyrosine kinase and autophosphorylation activity. Steady-state binding of EGF to the purified receptor revealed the presence of one class of binding sites exhibiting an apparent dissociation constant (Kd) of approx. 2 nM. When Angiotensin II was used as a receptor tyrosine kinase substrate the specific activity of the EGF induced kinase was 87 nmol/min per mg and the Km of the reaction was about 2 mM. Reconstitution of the EGF receptors into lipid vesicles was achieved by octylglucoside dialysis. Reconstitution of the receptor into pure dioleoylphosphatidylcholine (DOPC) vesicles had no effect on the EGF-binding properties in comparison to receptors in Triton X-100 micelles. Binding of EGF to the reconstituted receptor with ATP and Angiotensin II incorporated into the vesicles resulted in a five fold stimulation of the receptor kinase activity. The introduction of cholesterol, ranging from 10% to 50% (w/w), into DOPC vesicles resulted in an increase of the affinity of the receptor for its ligand. The Kd for EGF decreased from 1.8 nM in pure DOPC vesicles to 0.3 mM in DOPC/cholesterol (1:1 (w/w)) vesicles. With the introduction of small amounts (2% (w/w)) of phosphatidylinositol lipids into DOPC vesicles the Kd changed from 1.8 nM to 0.2 nM with phosphatidylinositol (PtdIns) and phosphatidylinositol 4,5-biphosphate (PtdIns4,5-P2) and to 0.1 nM in the case of phosphatidylinositol 4 phosphate (PtdIns4-P). No change in affinity was found when equal amounts of phosphatidylserine (PS) or phosphatidic acid (PA) were used.

Cholesterol and phospholipid efflux from cultured cells
Waddington, E. I., E. Boadu, et al. (2005), Methods 36(2): 196-206.
Abstract: The removal of phospholipids and cholesterol from tissues is the major mechanism mediating the initial assembly of high density lipoproteins (HDL), as well as being the main reason HDL are thought to protect against atherosclerosis. Investigations of the mechanisms of HDL assembly and testing of novel HDL-raising agents typically involve assays to determine phospholipid and/or cholesterol removal or "efflux" from cultured cells. The purpose of this chapter is to describe experimental protocols that can be used in the determination of cholesterol and phospholipid efflux from cultured cells by HDL apolipoproteins for the formation of new HDL particles, and the testing of novel HDL-raising therapies in vitro. A protocol is also provided for determining the size and nature of HDL particles formed in cell-conditioned medium using two-dimensional gel electrophoresis.

Cholesterol and phospholipid levels in erythrocyte membrane of patients with blood lipid disorders and hypertension
Koblik, T. (1990), Przegl Lek 47(11): 750-5.
Abstract: The aim of this paper was search for possible relationship between cholesterol and phospholipids in erythrocyte++ membrane and pathological entities i.e. hypertension and dyslipidemia. Both are the main risk factors of atherosclerosis and in both condition disturbances at the cell membrane level were detected. 124 persons (both men and women in a age group 20-59), employees of industrial enterprise were included into study. Standard questionnaire was performed as well as body weight and height, blood pressure, biochemical tests-lipids, cell membrane lipids serum and intracellular electrocytes as well as 24 h electrolyte urine excretion. The following findings were reported: cell membrane cholesterol concentration correlates with sex, age, body weight, systolic and diastolic blood pressure and triglycerydes HDL-cholesterol and serum phospholipids. The biggest influence on cholesterol concentration in cell membrane have the following factors: sex, age and serum triglycerides. The most important finding was that the lipid metabolism disturbances has impact on triglyceride elevation in serum and that arterial hypertension is connected with decreased cholesterol concentration in erytrocyte membrane.

Cholesterol and phospholipid levels of washed and percoll gradient centrifuged mouse sperm: presence of lipids possessing inhibitory effects on sperm motility
Tanphaichitr, N., Y. S. Zheng, et al. (1996), Mol Reprod Dev 43(2): 187-95.
Abstract: Levels of DNA, cholesterol, and phospholipids of mouse caudal epididymal and vas deferens sperm that were processed through simple washing and Percoll gradient centrifugation were measured. The DNA and cholesterol contents of washed sperm and Percoll gradient centrifuged (PGC) sperm (DNA = 3.6 +/- 0.3 pg/sperm and 3.4 +/- 0.3 pg/sperm, respectively; cholesterol = 0.219 +/- 0.057 nmole/microgram DNA and 0.224 +/- 0.030 nmole/microgram DNA, respectively, for washed and PGC sperm) were not significantly different from each other; however, the phospholipid level of PGC sperm was only one half of that of washed sperm (0.315 +/- 0.071 nmole/microgram DNA versus 0.720 +/- 0.075 nmole/microgram DNA, respectively). The presence of 0.3% bovine serum albumin (BSA) in the culture medium used in sperm washing did not change the cholesterol and phospholipid contents of washed sperm. Similarly, the cholesterol and phospholipid levels of washed sperm and PGC sperm that were further incubated in BSA-containing medium for 30 min remained the same. Interestingly, substantial amounts of lipids, as determined by the cholesterol and phospholipid levels, were released into the supernatants of the sperm washes, and sperm needed to be washed at least twice to ensure their stable levels of cholesterol and phospholipids. The lipid mixture in the first sperm wash supernatant was shown to have inhibitory effects on PGC sperm motility.

Cholesterol and phospholipid metabolism in macrophages
Tabas, I. (2000), Biochim Biophys Acta 1529(1-3): 164-74.
Abstract: Cholesterol-loaded macrophages are present at all stages of atherogenesis, and recent in vivo data indicate that these cells play important roles in both early lesion development and late lesion complications. To understand how these cells promote atherogenesis, it is critical that we understand how lesional macrophages interact with subendothelial lipoproteins, the consequences of this interaction, and the impact of subsequent intracellular metabolic events. In the arterial wall, macrophages likely interact with both soluble and matrix-retained lipoproteins, and a new challenge is to understand how certain consequences of these two processes might differ. Initially, the major intracellular metabolic route of the lipoprotein-derived cholesterol is esterification to fatty acids, but macrophages in advanced atherosclerotic lesions progressively accumulate large amounts of unesterified, or free, cholesterol (FC). In cultured macrophages, excess FC accumulation stimulates phospholipid biosynthesis, which is an adaptive response to protect the macrophage from FC-induced cytotoxicity. This phospholipid response eventually decreases with continued FC loading, leading to a series of cellular death reactions involving both death receptor-induced signaling and mitochondrial dysfunction. Because macrophage death in advanced lesions is thought to promote plaque instability, these intracellular processes involving cholesterol, phospholipid, and death pathways may play a critical role in the acute clinical manifestations of advanced atherosclerotic lesions.

Cholesterol and phospholipids content of yolk from fertilized and unfertilized hen eggs
Guedes, L. S., K. M. da-Silva, et al. (1992), Braz J Med Biol Res 25(4): 327-9.
Abstract: Three lipid-containing fractions (granules, low-density lipoproteins (LDL) and infranatant) of fertilized and unfertilized yolks were obtained from hen eggs, either from commercial sources or from Arbor acres hens kept by the Pena Branca Aviario Pernambuco and utilized fresh (laid during the previous 7 days). Total cholesterol (TC) and total phospholipid (TP) levels (mg/g yolk, reported as means +/- SD) were determined. In the yolk granules (insoluble fraction) the levels of TC (2.05 +/- 0.36) and TP (0.90 +/- 0.43) of fertilized egg yolks were similar to the levels of TC (2.20 +/- 0.41) and TP (0.90 +/- 0.14) of unfertilized eggs. The TC levels in the LDL from fertilized egg yolks (8.29 +/- 1.63) were not statistically different from those in unfertilized eggs (7.31 +/- 1.50). In contrast, TC was not detected in the infranatant fraction of unfertilized egg yolks, but was present in the infranatant fraction (1.39 +/- 0.69) of fertilized eggs. The TP levels of LDL (0.73 +/- 0.23) and infranatant (0.32 +/- 0.09) fractions of fertilized egg yolks were significantly lower than the levels of TP in the LDL (1.73 +/- 0.51) and infranatant (0.79 +/- 0.59) fractions of unfertilized eggs. Consequently, the TC/TP ratio (mol/mol) increased in the LDL and infranatant fractions of fertilized egg yolks when compared to unfertilized egg yolks. TC levels were similar in the total yolk of fertilized (10.76 +/- 1.32) and unfertilized (10.33 +/- 1.77) eggs, while the TP levels were significantly lower in the fertilized (1.92 +/- 0.17) than in unfertilized (3.43 +/- 0.97) eggs.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol and phospholipids in high density lipoproteins and their subfractions in a population in its second decade of life. The Burgos study
Jover Sanz, E. and J. C. Vella Ramirez (1992), An Esp Pediatr 37(6): 493-8.
Abstract: Decreased levels of high-density lipoproteins (HDL) are related to a risk of ischaemic heart disease and are measured as HDL-cholesterol (HDLc), whereas little attention has been paid to HDL-phospholipids (HDLph). Regarding HDL subfractions (HDL2, HDL3) and risk of ischaemic heart disease, there are few studies in the literature and these are contradictory, especially those performed in subjects that were in their second decade of life. This study consisted of 322 healthy volunteers between 11 and 19 years of age. The HDL fractions and HDL3 subfractions were separated by precipitation with polyethylene glycol at defined pH and concentration. Concentrations of cholesterol and triglycerides were measured by enzymatic methods, except for HDL2c and HDL2ph, which were calculated by subtraction. Forty-two percent of the children with parental history of ischaemic heart disease, but only 26% of the children without parental history of heart disease, exhibited HDL3ph levels lower than 0.95 mmol/l (74 mg/dl). Levels of HDLc, HDL3c and HDL2c are relatively constant in girls after puberty and levels of HDLph and HDL3ph are increased; levels of HDLph are relatively constant in boys after puberty while levels of HDLc, HDL3c and HDL2c are decreased. Our results suggest that serum levels of HDL3ph are potential markers for a risk of ischaemic heart disease, together with other more classic risk factors.

Cholesterol and phospholipids in human seminal plasma before and after vasectomy
Calzada, L. and E. L. Salazar (1992), Ginecol Obstet Mex 60: 42-4.
Abstract: Before and 2.6 months after vasectomy the alterations of secretory capacity and physiologic damage of the accessory genital glands, were evaluated by means of chemical analyses of certain constituents of seminal plasma such as free cholesterol, esterified cholesterol and phospholipids. The results of these studies showed that the ratio between the concentration of free cholesterol and esterified cholesterol is constant six months after vasectomy and the concentration of phospholipids decreases two months after vasectomy. These results are significant and may be important to know the alterations of secretory capacity of the human genital glands after vasectomy.

Cholesterol and plant sterol absorption: recent insights
von Bergmann, K., T. Sudhop, et al. (2005), Am J Cardiol 96(1A): 10D-14D.
Abstract: The recent discovery of transporters in the intestinal mucosa and the canalicular membrane has given new insights into the regulation of intestinal absorption as well as the biliary output of cholesterol and plant sterols. The 2 adenosine triphosphate (ATP)-binding cassette (ABC) half-transporters ABCG5 and ABCG8 are expressed in the mucosa cells and the canalicular membrane, and they resecrete sterols, especially absorbed plant sterols, back into the intestinal lumen and from the liver into bile. Defects of either of these cotransporters lead to the rare inherited disease of phytosterolemia, which is clinically defined by hyperabsorption and diminished biliary excretion of plant sterols. Furthermore, it has been recently demonstrated that the Niemann-Pick C1-Like 1 (NPC1L1) transporter is most likely responsible for the transport of cholesterol and plant sterols from the brush border membrane into the intestinal mucosa. Ezetimibe interferes with NPC1L1, reducing the intestinal uptake of cholesterol and plant sterols. These new findings contribute to our understanding of cholesterol and plant sterol concentrations in serum, and the effect of dietary and drug intervention to reduce serum concentrations of sterols.

Cholesterol and polyunsaturated acid enriched diet: effect on kinetics of the acrosome reaction in rabbit spermatozoa
Diaz-Fontdevila, M. and E. Bustos-Obregon (1993), Mol Reprod Dev 35(2): 176-80.
Abstract: In this study we examined the effect of cholesterol (Diet 2), cholesterol and fish oil (FO) polyunsaturated acid (Diet 3), and polyunsaturated acid (Diet 4) enriched diets upon the acrosome reaction (AR) of New Zealand White rabbit spermatozoa. Male rabbits fed with cholesterol alone or with FO increased their cholesterol and LDL-cholesterol serum levels after 15 days of diet. Ten semen samples were obtained after 2 months of diet. Our results suggest that hypercholesterolemia and hypertriglyceridemia in male rabbits could produce a decreased capacity of sperm AR after 4 h (0%, 0%, and 60% lower than the control), 6 h (0%, 68%, and 44%), or 8 h (58%, 52% and 32%) of incubation in capacitating medium. Another set of experiments were made with lysophosphatidylcholine (LPC), 80 micrograms/ml, and the same pattern of AR was seen. Nevertheless, the high cholesterol and total lipids (TL) levels in serum did not affect the cholesterol levels in seminal plasma (SP) but affect the SP total lipids. The diminished capacity of rabbit sperm to undergo the AR was not reverted by in vitro incubation with the Shinitsky medium for cholesterol depletion (MDC). These results indirectly suggest that the cholesterol/phospholipid ratio in hypercholesterolemic sperm is similar to that of controls and are in agreement with preliminary studies made in our laboratory that evidenced the same cholesterol/phospholipid ratio in rabbit sperm from hypercholesterolemic animals than from controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol and prostate cancer
Freeman, M. R. and K. R. Solomon (2004), J Cell Biochem 91(1): 54-69.
Abstract: Cholesterol is a neutral lipid that accumulates in liquid-ordered, detergent-resistant membrane domains called lipid rafts. Lipid rafts serve as membrane platforms for signal transduction mechanisms that mediate cell growth, survival, and a variety of other processes relevant to cancer. A number of studies, going back many years, demonstrate that cholesterol accumulates in solid tumors and that cholesterol homeostasis breaks down in the prostate with aging and with the transition to the malignant state. This review summarizes the established links between cholesterol and prostate cancer (PCa), with a focus on how accumulation of cholesterol within the lipid raft component of the plasma membrane may stimulate signaling pathways that promote progression to hormone refractory disease. We propose that increases in cholesterol in prostate tumor cell membranes, resulting from increases in circulating levels or from dysregulation of endogenous synthesis, results in the coalescence of raft domains. This would have the effect of sequestering positive regulators of oncogenic signaling within rafts, while maintaining negative regulators in the liquid-disordered membrane fraction. This approach toward examining the function of lipid rafts in prostate cancer cells may provide insight into the role of circulating cholesterol in malignant growth and on the potential relationship between diet and aggressive disease. Large-scale characterization of proteins that localize to cholesterol-rich domains may help unveil signaling networks and pathways that will lead to identification of new biomarkers for disease progression and potentially to novel targets for therapeutic intervention.

Cholesterol and psychological well-being
Wardle, J. (1995), J Psychosom Res 39(5): 549-62.
Abstract: The debate about possible adverse effects associated with low or lowered serum cholesterol has raised important scientific questions concerning the links between lipids and behaviour. One of the most unexpected findings has been an association between cholesterol-lowering treatment and accidental death. A similar association has also emerged among the prospective cohort studies, with higher-than-expected numbers of suicide deaths in the lowest cholesterol groups. These observations have prompted speculation that behavioural or emotional disturbances could be part of the process linking lipids and accidental death. In this paper, the epidemiological literature is reviewed briefly, then the evidence for depression as a mediating condition is discussed. Two conclusions are drawn from this review of the literature. One is that understanding the relationship between the biology of lipids and the psychobiology of mood is demonstrably an important scientific and public health issue. The second is that the introduction of new treatments or preventive programmes should include a careful evaluation of the psychological as well as the physical effects.

Cholesterol and public policy
LaRosa, J. C. (1994), Atherosclerosis 108 Suppl: S137-41.
Abstract: Cholesterol lowering in both primary and secondary prevention has been clearly demonstrated to lower coronary morbidity and, in secondary prevention, to lower coronary mortality as well. Putative dangers of cholesterol lowering remain unproven. Population studies linking low cholesterol to noncoronary mortalities do not demonstrate cause-and-effect relations. In fact, based on current studies, the opposite is more likely to be the case. Neither gender nor age should automatically exclude persons from cholesterol screening. Drug intervention, however, should be used conservatively, particularly in young adults and the elderly. Drugs should be used only after diet and lifestyle interventions have failed. The evidence linking high blood cholesterol to coronary atherosclerosis and cholesterol lowering to its prevention is broad-based and definitive. Concerns about cholesterol lowering and spontaneously low cholesterols should be pursued but should not interfere with the implementation of current public policies to reduce the still heavy burden of atherosclerosis in Western society.

Cholesterol and Recurrent Events: a secondary prevention trial for normolipidemic patients. CARE Investigators
Pfeffer, M. A., F. M. Sacks, et al. (1995), Am J Cardiol 76(9): 98C-106C.
Abstract: Although elevated plasma cholesterol levels represent a well-established and significant risk for developing atherosclerosis, there is a wide spectrum of cholesterol levels in patients with coronary artery disease (CAD). Most secondary prevention studies have generated convincing evidence that cholesterol reduction in patients with high cholesterol levels is associated with improved clinical outcome by reducing risk of further cardiovascular events. However, other risk factors may play a prominent role in the pathogenesis of coronary disease in the majority of patients with near-normal cholesterol values. The Cholesterol and Recurrent Events (CARE) study was designed to address whether the pharmacologic reduction of cholesterol levels with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, pravastatin, would reduce the sum of fatal coronary artery disease (CAD) and nonfatal myocardial infarction (MI) in patients who have survived an MI yet have a total cholesterol value < 240 mg/dl (< 6.2 mmol/liter). The other inclusion criteria for this study were age 21-75 years, low density lipoprotein (LDL) cholesterol levels of 115-174 mg/dl (3.0-4.5 mmol/liter), and fasting serum triglyceride levels < 350 mg/dl (< 4.0 mmol/liter). A total of 4,159 eligible consenting patients without other study exclusions were then randomly assigned to receive either pravastatin 40 mg daily or matching placebo in addition to their individualized conventional therapy. The trial was designed to have a median follow-up of 5 years. Study endpoints will be evaluated with respect to predefined subgroups according to baseline lipid values, age, gender, prior cardiovascular risk factors, and history.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol and risk of stroke
Boysen, G. and E. Lindenstrom (1996), Lancet 347(9003): 762.

Cholesterol and screening of asymptomatic adults
Muldoon, M. F. (1990), Ann Intern Med 112(5): 384-5.

Cholesterol and serotonin indices in depressed and suicidal patients
Sarchiapone, M., G. Camardese, et al. (2001), J Affect Disord 62(3): 217-9.
Abstract: BACKGROUND: Prolactin and cortisol responses to d-fenfluramine challenge of central serotonin are reduced in depressed and suicidal patients. Low serum cholesterol levels are also reported in suicidal behavior. Thus, we examined for a relationship between serum cholesterol and fenfluramine challenge responses in patients with depression and/or attempted suicide. METHODS: We studied 12 patients and six controls. Blood was drawn for baseline serum cholesterol and the d-fenfluramine challenge test performed. RESULTS: Serum cholesterol levels were significantly lower in suicidal patients than in either non-suicidal patients or controls. However, neither the prolactin nor cortisol responses to d-fenfluramine correlated significantly with serum cholesterol levels. CONCLUSION: No relationship was found between serum cholesterol and these peripheral indices of serotonergic function.

Cholesterol and serotonin: seeking a possible link between blood cholesterol and CSF 5-HIAA
Ringo, D. L., S. E. Lindley, et al. (1994), Biol Psychiatry 35(12): 957-9.

Cholesterol and serum albumin levels as predictors of cross infection, death, and length of hospital stay
Delgado-Rodriguez, M., M. Medina-Cuadros, et al. (2002), Arch Surg 137(7): 805-12.
Abstract: HYPOTHESIS: The levels of cholesterol, its fractions (high-density lipoprotein cholesterol HDL-C and low-density lipoprotein cholesterol LDL-C), and serum albumin reflect nutritional status and are related to in-hospital death, nosocomial infection, and length of stay in the hospital. DESIGN: A prospective cohort study of hospitalized patients. SETTING: The Service of General Surgery of a tertiary hospital. PATIENTS: A consecutive series of 2989 patients admitted for more than 1 day. MAIN OUTCOME MEASURES: Nosocomial infection, in-hospital death, and length of stay. RESULTS: During follow-up, 62 (2%) of the patients died, 382 (13%) developed a nosocomial infection, and 257 (9%) developed a surgical site infection. Serum albumin (lowest quintile vs highest quintile: adjusted odds ratio OR, 1.9; 95% confidence interval, 1.2-2.9) and HDL-C (lowest quintile vs highest quintile: OR, 2.0; 95% confidence interval, 1.3-3.0) levels showed an inverse and highly significant relationship with nosocomial infection (mainly due to surgical site infection) in crude and multivariate analyses (controlling for the Study on the Efficacy of Nosocomial Infection Control SENIC index, the American Society of Anesthesiologists' score, cancer, and age). Regarding total and LDL-C levels, only their lowest quintiles increased the risk of nosocomial infection. Serum albumin and HDL-C levels showed an inverse trend (P<.001) with mortality, with high multivariate-adjusted ORs in the lowest quintile (serum albumin: OR, 5.8; 95% confidence interval, 0.8-44.6; HDL-C: OR, 7.2; 95% confidence interval, 0.9-55.0), whereas no trend was appreciated with other cholesterol fractions or ratios. Serum albumin, HDL-C, and LDL-C levels showed independent, significant (P<.001), and inverse relationships with length of stay. CONCLUSION: The levels of serum albumin and cholesterol fractions, mainly HDL-C, which are routinely measured at hospital admission, are predictors of in-hospital death, nosocomial infection, and length of stay.

Cholesterol and sphingolipid enhance the Triton X-100 insolubility of glycosylphosphatidylinositol-anchored proteins by promoting the formation of detergent-insoluble ordered membrane domains
Schroeder, R. J., S. N. Ahmed, et al. (1998), J Biol Chem 273(2): 1150-7.
Abstract: Glycosylphosphatidylinositol (GPI)-anchored proteins can be isolated from both cells and sphingolipid and cholesterol-rich liposomes (SCRLs) in association with detergent-insoluble membranes. We found previously that detergent insolubility of lipids was characteristic of phases in which lipid acyl chains are ordered. We presented evidence that GPI-anchored proteins are insoluble because they associate with cholesterol and sphingolipid-rich lipid domains with properties similar to the liquid-ordered phase. Here, this model was tested by a variety of approaches. First, we demonstrated that saponin, which removes cholesterol from cell membranes and allows solubilization of GPI-anchored proteins by Triton X-100, had the same effect on the GPI-anchored protein alkaline phosphatase (PLAP) in SCRLs of appropriate lipid composition. The similarity of saponin action in cells and simple liposomes suggests that the compound disrupts protein-lipid interactions. However, direct interactions between PLAP and cholesterol were not needed for insolubility, because the protein was also insoluble in cholesterol-free liposomes containing lipid in an ordered phase. Instead, cholesterol acted by greatly enhancing the formation of a detergent-insoluble phase by sphingolipids, which have a tendency to form ordered phases. We propose that saponin solubilizes GPI-anchored proteins because the lipid composition of cell membranes (and the SCRLs used above) supports ordered phase formation in the presence but not the absence of cholesterol. Supporting this model, saponin did not promote Triton X-100 solubilization of PLAP in SCRLs with sphingolipid levels high enough to allow ordered phase formation in the absence of cholesterol. We also showed that two additional GPI-anchored proteins are detergent-insoluble in SCRLs and that detergent does not artifactually create ordered domains or cause components of solubilized membranes to associate with detergent-resistant membranes present in separate bilayers in the same lysate. We conclude that the ordered domain model explains the behavior of detergent-resistant membranes in liposomes and cells.

Cholesterol Articles and Abstracts

Cholesterol Journal Articles