Disease relevance of CHOL

• A strain of pigs bearing three immunogenetically defined lipoprotein-associated markers (allotypes), designated Lpb5, Lpr1, and Lpu1, has marked hypercholesterolemia on a low fat, cholesterol-free diet [1].
• Resistance to arteriosclerosis in pigs with von Willebrand's disease. Spontaneous and high cholesterol diet-induced arteriosclerosis [2].
• This provides a mechanism by which cholesterol gallstones could become secondarily pigmented [3].
• BACKGROUND & AIMS: Impaired gallbladder emptying occurs in patients undergoing bile salt therapy for cholesterol gallstone dissolution and in patients with cirrhosis who have elevated serum bile salt concentrations [4].
• The purpose of the present study was to determine if grapefruit pectin affects cholesterol levels and atherogenesis of animals with established hypercholesterolemia [5].

Psychiatry related information on CHOL

• Recent epidemiological studies show a strong reduction in the incidence of Alzheimer's disease in patients treated with cholesterol-lowering statins [6].
• One of three indices of exploratory behavior was significantly greater in the L pigs that received cholesterol compared with L pigs that did not receive cholesterol [7].
• Effect of clofibrate, cholestyramine, cholesterol and feeding pattern on the diurnal variation of cholesterol 7 alpha-hydroxylation in swine [8].
• Several serum chemical values (creatinine, triglycerides, cholesterol, blood urea nitrogen, and lactate dehydrogenase) were significantly influenced by feed deprivation, but not by feed and water deprivation [9].
• Enforced increase of motor activity in rats (60 or 120-day adaptation on a treadmill - 18 m/min/3 hr/day) results in a decreased tissue cumulation of lipids including cholesterol despite their increased formation [10].

High impact information on CHOL

• Thus, cell-surface receptors for HDL on hepatocytes are chief partners in the regulation of cholesterol homeostasis [11].
• We suggest that FXR (BAR) is the endogenous bile acid sensor and thus an important regulator of cholesterol homeostasis [12].
• Eight miniature pigs underwent regional endothelial denudation of the left anterior descending coronary artery and were then fed a high cholesterol diet [13].
• These data provide direct evidence that arterial wall macrophages express modified LDL receptors in vivo, contain epitopes found in oxidized-LDL and are capable of oxidizing LDL even when maximally loaded with cholesterol [14].
• Effects of cocaine on epicardial coronary artery reactivity in miniature swine after endothelial injury and high cholesterol feeding. In vivo and in vitro analysis [13].

Chemical compound and disease context of CHOL

• METHODS: Cholesterol was compressed into pellets at 2500 psi, producing a pellet that behaved like human cholesterol gallstones in regard to penetration of solutes into the stone [3].
• Platelet thrombus formation at both high and low shear rates decreased as total and LDL cholesterol levels were reduced with pravastatin [15].
• In cholesterol-fed animals, endothelium-dependent relaxations to aggregating platelets, serotonin, ADP, bradykinin, thrombin, and the calcium ionophore A23187 were depressed in LAD (atherosclerosis), while the relaxations to aggregating platelets, serotonin and ADP were depressed in LCX (hypercholesterolemia) [16].
• Acute effects of topical methyl tert-butyl ether or ethyl propionate on gallbladder histology in animals: a comparison of two solvents for contact dissolution of cholesterol gallstones [17].
• However, this same broth supplemented either with vesicles made from cholesterol and phosphatidylcholine or with washed erythrocytes was a good culture medium for the spirochete [18].

Biological context of CHOL

• Dose response curves varying Ab concentration showed that CHOL PEC required higher concentrations of Ab to effect phagocytosis and lysis than did CONT PEC [19].
• These findings suggest that, compared with the apical membranes of absorptive cells, those of M cells have a low protein to lipid ratio and an abundance of morphologically detectable cholesterol except in domains involved in endocytosis [20].
• Addition of cholesterol, low density or very low density lipoproteins to the lipoprotein-deficient culture medium, inhibited the expression of cyst wall proteins, the generation of encystation-specific vesicles, and cyst wall biogenesis [21].
• 4) Systemic factors: There is clinical and experimental evidence to suggest that various systemic factors at the time of plaque rupture may enhance thrombogenicity (i.e., levels of epinephrine, levels of serum cholesterol, impaired fibrinolysis) [22].
• Hematocrits among cholesterol-fed animals (47.6 +/- 1.2%) were lower than those of controls (54.8 +/- 1.3%, p less than 0.05) probably as a result of the cholesterol-induced hemolytic anemia which has been reported by others in this species [23].

Anatomical context of CHOL

• Vascular endothelial growth factor treatment was ineffective in the CHOL group (circumflex/left anterior descending coronary artery blood flow ratios: 0.95 [rest] and 0.74 [pace] before-after treatment; P < .05 compared with the NORM group) [24].
• The integrated porcine hepatocytes provide functional LDL receptors that lower serum cholesterol in the WHHL rabbit by 30-60% for at least 100 days [25].
• Lipoprotein preparations from plasmas of both C+- and C--fed animals inhibited NK cell activity, but suppression was not due to lipoprotein cholesterol content [26].
• Accumulation of unconjugated bilirubin in cholesterol pellets implanted in swine gallbladders [3].
• M-cell apical plasma membranes were rich in cholesterol, displaying numerous filipin-induced membrane lesions in thin sections and freeze-fracture replicas [20].

Associations of CHOL with chemical compounds

• The main lipid classes in the SC are ceramides (CER), free fatty acids (FFA) and cholesterol (CHOL) [27].
• For this purpose lipid phase behavior of mixtures of CHOL and total ceramide fraction was compared with that of mixtures of CHOL and a ceramide mixture lacking CER 1 [28].
• METHODS: Eighteen Yucatan pigs were fed either a normal (NORM, n=6) or a high-cholesterol diet, with (CHOL-ARG, n=6) or without (CHOL, n=6) L-arginine (100 mg/kg/day), throughout the experiment [29].
• METHODS AND RESULTS: Yucatan pigs were fed either a normal (NORM group; n=7) or high-cholesterol diet, with (CHOL-ATR group; n=7) or without (CHOL group; n=6) atorvastatin (3 mg/kg per day) for 13 weeks [30].
• When palmitic acid (PA) was included, the phase behaviour of the CHOL/CER(1 + 2)/PA mixture was more complex [31].

Physical interactions of CHOL

• The Niemann Pick-C1 (NPC-1) protein is essential for intracellular transport of cholesterol derived from low-density lipoprotein import in mammalian cells [32].
• Staining for IGF-1 and IGF binding protein 2 was increased (P<0.05) in arterioles of cholesterol-fed pigs [33].
• Reconstitution of the myometrial oxytocin receptor into proteoliposomes. Dependence of oxytocin binding on cholesterol [34].

Regulatory relationships of CHOL

• Because of the rapid growth of uterus during early pregnancy and differences in placentation between swine and humans, we hypothesized that SR-BI may be expressed in porcine endometrium to take up HDL cholesterol [35].
• As LDL receptor gene expression in other tissues is negatively regulated by the abundance of intracellular free cholesterol, we assessed the impact of concomitant pretreatment of granulosa-luteal cells with an exogenous soluble sterol (25-hydroxycholesterol, 1 and 10 microM) [36].
• Together, the present findings show that in Leydig cells from intact animals, EGF enhances the gonadotropin action on testosterone formation through an increase in the availability of cholesterol substrate in the mitochondria as well as an increase in the activity of 3 beta-HSDI [37].
• Superoxide dismutase also inhibited cholesterol 7 alpha-hydroxylation in the system where superoxides were generated by enzymatic or nonenzymatic means in the absence of NADPH-generating system [38].
• We now propose that membrane cholesterol can modify and inhibit linoleic acid-mediated endothelial cell dysfunction [39].

Other interactions of CHOL

• Control animals received MBP mixed with PC and CHOL or MBP alone, in CFA [40].
• By single-stranded conformational polymorphism (SSCP) analysis, we studied the relationship between LDL receptor genotype and plasma cholesterol phenotype [41].
• Immunologically defined alleles of the pig apolipoprotein B (ApoB) locus (apoB) are correlated with different blood cholesterol levels and predisposition towards premature coronary heart disease [42].
• Steroidogenic acute regulatory protein (StAR) mediates cholesterol transport into the mitochondria and is essential for ovarian steroidogenesis [43].
• Serum CRP correlated directly with plasma total cholesterol (R = 0.727, P = 0.041) and accumulation of SRA-positive macrophages (R = 0.938, P < 0.001) in RCA of HF pigs [44].

Analytical, diagnostic and therapeutic context of CHOL

• Collateral-dependent myocardial perfusion, adjusted for baseline, was significantly reduced in the CHOL group (-0.27+/-0.07 mL/min per gram versus NORM; P<0.001) as well as the CHOL-ATR group (-0.35+/-0.07 mL/min per gram versus NORM; P<0.001) [30].
• Reduction of serum cholesterol in Watanabe rabbits by xenogeneic hepatocellular transplantation [25].
• A histomorphometric study of the epithelial cells showed significantly higher values for nuclear density (P < 0.01) and nuclear (P < 0.05) and cytoplasmic (P < 0.05) areas in the cholesterol gallstone than the control group [45].
• We examined the effects of gallbladder mucosal lipid absorption on lipid composition and cholesterol crystallization in bile [45].
• Luminal narrowing was not affected by anticoagulation therapy, antiplatelet drugs, cholesterol level, or stent sizing [46].

References