Disease relevance of cholesterol

• However, both groups were older and had higher CHOL and prevalence of hypertension than group 0 [1].
• Reverse cholestrol transport substantially influences the individual risk of coronary heart disease in hypercholesterolaemic patients [2].
• The percentage of error in sera of patients with atherosclerosis and chronic renal failure was higher than in controls with a similar mean (C/TG)VLDL ratio [3].
• RESULTS: Physically active former athletes had significantly lower mean overweight (BMI, fat percentage, WHR), better spectrum of atherogenesis indicators (CHOL, HDL-C, TG, TG:HDL-C ratio) and lower oxidative stress (oxLDL, oxLDL:LDL-C ratio, DC) values than sedentary ex-athletes [4].
• CHL markedly prolonged the QT interval, whereas FLX significantly shortened the QT interval and reduced arrhythmias in the FLX and CHL/FLX hearts [5].
• These recent findings emphasize the importance of intraplaque hemorrhage as a contributor of free cholesterol in plaques and point to its provocative role in lesion destabilization [6].
• A growing amount of evidence suggests a mechanistic link between cholesterol metabolism in the brain and the formation of amyloid plaques in AD development [7].
• Ischemic heart disease mortality was not significantly associated with total cholesterol levels in all men (HR, 1.05), but a significant positive association in men without CVD and a slight nonsignificant inverse association in men with CVD were observed (HR, 1.47 vs 0.84) [8].
• Based on the result of this large scale community study, HCV viremia appears to be associated with lower serum cholesterol and triglyceride levels which implies that HCV itself might play a significant role on serum lipid profile of patients with chronic HCV infection [9].
• These observations suggest that the neuropathogenesis of prion diseases results from PrPSc altering cholesterol-sensitive processes [10].

Psychiatry related information on cholesterol

• Significant associations were found between physical activity (METs), SBP, DBP, hypertension, CHOL, HDL-C, TG, TG:HDL-C ratio, oxLDL, oxLDL:LDL-C ratio, DC and hsCRP [4].
• After controlling, for age, cigarette smoking, alcohol drinking and puberty development, shorter body height was the strongest predictor of total CHOL, LDL-C and ApoB concentrations among boys [11].
• Significant increases in total CHO (25.4 +/- 17.5 mg/dl, mean +/- SD), LDL-CHO (17.1 +/- 14.5) and LDL (43.9 +/- 37.6) were observed in C-group but were attenuated in the T-group [12].

High impact information on cholesterol

• The HDL: the good cholestrol carriers [13]?
• BACKGROUND: The form of vitamin D (vitamin D3) in fortified milk and the provitamin D produced by the body undergo metabolic activation to a biologically active form, 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] [14].
• Elevated HDL-cholesterol (C) and apo AI are associated with decreased coronary artery disease (CAD) risk [15].
• By redesigning conventional cationic liposomes, incorporating cholesterol (chol) as the neutral lipid and preparing them as multilamellar vesicles (MLV), we increased the efficiency of cationic liposome:DNA complex (CLDC)-mediated gene delivery [16].
• Monocytoid cell binding to aortic endothelium was significantly increased in Chol (P < .001 versus Cont); binding was markedly reduced in arginine-fed hypercholesterolemic animals (P < .05, Arg versus Chol) [17].

Chemical compound and disease context of cholesterol

• Groups 1 and 2 were similar in age, sex, smoking status, hypertension prevalence, fasting plasma glucose, and serum cholesterol (CHOL) [1].
• The response was studied in five persons with average cholestrol distributions and five persons with cholesterol distributions associated with high risk of coronary heart disease [18].
• CONCLUSION: The prevalence of obesity is slightly higher than reported in previous studies in Taiwan. The obese subjects had various abnormal lipoprotein metabolic characteristics, such as higher CHOL, TG, and apo B and lower HDL-C levels than non-obese subjects [19].
• Safety of low-density lipoprotein cholestrol reduction with atorvastatin versus simvastatin in a coronary heart disease population (the TARGET TANGIBLE trial) [20].
• A peptide corresponding to the 23 N-terminal amino acid residues of the human immunodeficiency virus type-1 (HIV-1) gp41 has the capacity to induce intervesicular lipid mixing in large unilamellar liposomes composed of dioleoylphosphatidylcholine (DOPC), dioleoylphosphatidylethanolamine (DOPE) and cholesterol (CHOL) (molar ratio, 1:1:1) [21].
• Combination therapy using cholesterol absorption (NPC1L1) inhibitor (ezetimibe) and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) provides a powerful novel strategy for the prevention and treatment of hypercholesterolemia [22].

Biological context of cholesterol

• The receptor for LDL was functional in maintaining Chol homeostasis, as demonstrated by feedback inhibition of Chol synthesis after culture with LDL or very low density lipoprotein (VLDL) [23].
• In 1340 women studied 6-12 wk postpartum (PP-GDM group), chol and LDL-chol were similar to levels in 43 postpartum control subjects without prior GDM [24].
• Cationic liposomes containing DC-6-14, DOPE, and Chol in molar ratios of 1:0.75:0.75 and 1:1:0.8 maintained efficient transfection activity under serum-containing conditions in HRA, mEIIL, and ES-2 cell lines in vitro, as determined by luciferase assay [25].
• Thus, vigorous regular walking resulted in a reduction of body fate stores, endogenous insulin requirements, and food intake, and perhaps improved the ability to eliminate cholestrol by increasing the plasma high density lipoprotein fraction [26].
• To test this hypothesis, we examined the differentiation, proliferation, or apoptosis profile of smooth muscle cell (SMC) and adventitial cell response to a mild injury induced via a Fogarty catheter in the carotid artery of adult rabbits that had been fed a standard chow or 0.5% CT-enriched diet starting 4 weeks before the lesion [27].

Anatomical context of cholesterol

• Incubation with native lipoproteins did not lead to accumulation of esterified Chol by macrophages [23].
• These markers are absent in similar difference spectra recorded from the nAChR reconstituted into EPC membranes lacking both Chol and DOPA, indicating that the nAChR cannot undergo conformational change in response to agonist binding [28].
• Likelihood ratio tests revealed the presence of significant (P < .05) cross-trait resemblance between body fat (BMI and SF6) and all lipid traits except CH and also between fat distribution (TER and TER-sf) and CH/HDL and CH-HDL [29].
• Caveolins transport cholestrol to and from caveolae, and they regulate the activity of signaling proteins that reside in caveolae [30].
• However, the P/C molar ratio is higher in the retroviral envelope than in the plasma membrane where they originate, and higher than in the nuclear envelope [31].

Associations of cholesterol with other chemical compounds

• The increment in the glucose area under the curve with the RPa diet was positively related to baseline cholesterol synthesis (eg, lathosterol; r = 0.480, P < 0.05) and negatively to absorption (for cholestanol; r = -0.520, P < 0.05) [32].
• The specificity of cholesterol regulation for Ca(2+) entry was confirmed using thapsigargin studies [33].
• No significant linear correlations were found between reductions in LDL cholesterol and soy protein ingestion or isoflavone intakes [34].
• Cholesterol depletion of macrophages with methyl-beta-cyclodextrin normalized FC content between the two genotypes and their response to LPS; cholesterol repletion of macrophages resulted in increased cellular FC accumulation and enhanced cellular response to LPS [35].
• On the other hand, 27-hydroxycholesterol, rather than cholesterol itself or biosynthetic precursors of cholesterol, stimulates the rapid inactivation of HMGR in response to high levels of cholesterol [36].
• We found that in desmosterol cells, Src kinase phosphorylated Cav1 at Tyr(14) more avidly than in cholesterol cells [37].
• Recently an important role for ABCA1, a cellular cholesterol transporter, has emerged in regulating cholesterol homeostasis and insulin secretion in pancreatic beta cells [38].
• Through adenosine A2A receptor activation, MTX promotes reverse cholesterol transport and limits foam cell formation in THP-1 macrophages [39].
• Since hydroxymethylglutaryl-CoA (HMG-CoA) reductase is the key enzyme in cholesterol synthesis and transcriptionally controlled by SREBP-2 we measured its mRNA levels, being 3- to 4-fold higher in NAFLD compared to controls, without any difference between NASH and steatosis patients [40].
• Atorvastatin therapy or squalene synthase inhibition in vivo attenuated StAR overexpression, mitochondrial cholesterol loading, and mGSH depletion, protecting ob/ob mice from I/R-mediated liver injury [41].
• Non-cholesterol sterols reflecting cholesterol synthesis (cholestenol, desmosterol, and lathosterol) were higher, and those reflecting cholesterol absorption (cholestanol and plant sterols) were lower in subjects with NAFLD than in controls, independent of body mass index [42].
• We observed that TCPOBOP-treated mice excreted more HDL cholesterol-derived bile acids in their faeces [43].

Gene context of cholesterol

• There has been concern that large, CE-rich HDL(2) generated by CETP inhibition might impair reverse cholesterol transport [44].
• ACAT1 is an endoplasmic reticulum cholesterol sensor and contains a signature motif characteristic of the membrane-bound acyltransferase family [45].
• The function of this transporter and the results of the genetic study taken together indicate that in gallstone-susceptible carriers of the ABCG8 19H allele, cholesterol cholelithiasis is secondary to increased hepatobiliary cholesterol secretion [46].
• Treatment of LXRalpha(-/-)apoE(-/-) mice with synthetic LXR ligand ameliorates the cholesterol overload phenotype and reduces atherosclerosis [47].
• By contrast, cholesterol depletion, which impairs lipid raft formation and clathrin-independent endocytosis, suppresses the rab-10 but not the lin-10 phenotype, suggesting that RAB-10 functions after clathrin-independent endocytosis [48].
• Lower 27-HC levels were associated with elevated cholesterol oxidation products in macrophages and plasma of chimeric Npc1-/- mice and with increased oxidative stress [49].
• These results suggest that seladin-1-dependent cholesterol synthesis reduces membrane-aggregate interaction and cell damage associated to amyloid-induced imbalance of cytosolic Ca2+ [50].
• Current evidence suggests that ABCA1-mediated cholesterol efflux to apoA-I involves mobilization of cholesterol from plasma membrane, endoplasmic reticulum, trans-Golgi network, late endocytic and lysosomal compartments, and cholesteryl ester droplets [51].
• The short-term effects of statins on cholesterol homeostasis were not associated with the SLCO1B1 polymorphism [52].
• We show that canalicular membranes of cholestatic Atp8b1-deficient mice have a dramatically reduced cholesterol to phospholipid ratio, i.e. 0.75 +/- 0.24 versus 2.03 +/- 0.71 for wild type [53].
• Trans-intestinal cholesterol excretion is impaired in mice lacking Abcg5 (-4%), suggesting that the cholesterol transporting Abcg5/Abcg8 heterodimer is involved in this pathway [54].
• Given that DISP3 is highly expressed in Purkinje cells, hippocampal neurons, and retinal ganglion cells and that its overexpression results in increased cholesterol levels, it is tempting to postulate that DISP3 may contribute to cholesterol homeostasis in neural cell types [55].

Analytical, diagnostic and therapeutic context of cholesterol

• The turnover of 125I-labeled low density lipoprotein (LDL) and the total body balance of cholestrol were studied in a 6-yr-old girl with the homozygous form of familial hypercholesterolemia (FH) before and after the surgical creation of an end-to-side portacaval shunt [56].
• We conclude that the serum levels of CH, TG and LDL do not seem to be related to restenosis after PTCA [57].
• We examined three major components of surfactant, surfactant protein A (SP-A), disaturated phospholipids (DSP), and cholesterol (CHOL) in bronchoalveolar lavage (BAL) fluid from 12 healthy men before and after exercise [58].
• We measure the interactions between TX and an equimolar mixture of sphingomyelin (SM), cholesterol (Cho), and 1-palmitoyl-2-oleoyl-3-sn-glycero-phosphatidylcholine (POPC) (1:1:1, mol) by means of isothermal titration calorimetry [59].
• These studies demonstrate that a cholestrol-enriched, atherogenic diet causes profound and reversible changes in the lipid composition, membrane fluidity, and morphology of red cells in dogs [60].

References