| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Exchanging partially hydrogenated fat for palmitic acid in the diet increases LDL-cholesterol and endogenous cholesterol synthesis in normocholesterolemic women Sundram, K., M. A. French, et al. (2003), Eur J Nutr 42(4): 188-94. Abstract: Partial hydrogenation of oil results in fats containing unusual isomeric fatty acids characterized by cis and trans configurations. Hydrogenated fats containing trans fatty acids increase plasma total cholesterol (TC) and LDL-cholesterol while depressing HDL-cholesterol levels. Identifying the content of trans fatty acids by food labeling is overshadowed by a reluctance of health authorities to label saturates and trans fatty acids separately. Thus, it is pertinent to compare the effects of trans to saturated fatty acids using stable isotope methodology to establish if the mechanism of increase in TC and LDL-cholesterol is due to the increase in the rate of endogenous synthesis of cholesterol. Ten healthy normocholesterolemic female subjects consumed each of two diets containing approximately 30% of energy as fat for a fourweek period. One diet was high in palmitic acid (10.6% of energy) from palm olein and the other diet exchanged 5.6% of energy as partially hydrogenated fat for palmitic acid. This fat blend resulted in monounsaturated fatty acids decreasing by 4.9 % and polyunsaturated fats increasing by 2.7%. The hydrogenated fat diet treatment provided 3.1% of energy as elaidic acid. For each dietary treatment, the fractional synthesis rates for cholesterol were measured using deuterium-labeling procedures and blood samples were obtained for blood lipid and lipoprotein measurements. Subjects exhibited a higher total cholesterol and LDL-cholesterol level when consuming the diet containing trans fatty acids while also depressing the HDL-cholesterol level. Consuming the partially hydrogenated fat diet treatment increased the fractional synthesis rate of free cholesterol. Consumption of hydrogenated fats containing trans fatty acids in comparison to a mixtur e of palmitic and oleic acids increase plasma cholesterol levels apparently by increasing endogenous synthesis of cholesterol. |
| Excision and drainage of cholesterol granulomas of the petrous apex with preservation of hearing under computer-assisted navigation surgery (CANS) Domeisen, H., M. Caversaccio, et al. (2000), Schweiz Med Wochenschr Suppl 125: 67S-70S. Abstract: Diagnosis of cholesterol granuloma of the petrous apex has become easier today with new imaging techniques such as MRI and CT. The therapy of choice is surgery, which is still considered a delicate procedure. The objective is to demonstrate hearing-preserving excision and drainage of cholesterol granulomas of the petrous apex using the Bernese system of computer-assisted navigation surgery. Between 1995 and 1999, 3 patients with severe temporal headache, tinnitus and nonspecific vertigo had surgery for cholesterol granuloma of the petrous apex with drainage and excision in the University ENT Clinic, Berne. In the first patient, a combined transmastoidal and transtemporal approach was adopted with infralabyrinthine and subcochlear partial petrosectomy and extirpation of the granuloma in the petrous apex (surgery time 7 h). In the following 2 patients computer-assisted navigation surgery was used and transmastoidal infralabyrinthine-subcochlear drainage and excision of the granuloma in the petrous apex was performed after antefacial hypotympanal drilling with partial exposure of the internal carotid artery (surgery time 2.5 h). After surgery patients were rapidly releaved of symptoms. Postoperative CT showed the newly aerated cells in the petrous apex with permanent drainage. Hearing was preserved with slight residual conductive loss. The surgical method of choice for hearing-preserving excision and drainage is made through an infralabyrinthine-subcochlear approach. The application of computer-assisted navigation surgery in the lateral skull base allows permanent intraoperative monitoring of the precise position of the microsurgical instruments (accuracy < 1 mm) giving a high security level for minimally invasive function preserving surgery. |
| Exclusion of a cholesterol analog from the cholesterol-rich phase in model membranes Loura, L. M., A. Fedorov, et al. (2001), Biochim Biophys Acta 1511(2): 236-43. Abstract: Vesicles of phosphatidylcholine/cholesterol mixtures show a wide composition range with coexistence of two fluid phases, the 'liquid disordered' (cholesterol-poor) and 'liquid ordered' (cholesterol-rich) phases. These systems have been widely used as models of membranes exhibiting lateral heterogeneity (membrane domains). The distributions of two fluorescent probes (a fluorescent cholesterol analog, NBD-cholesterol, and a lipophilic rhodamine probe, octadecylrhodamine B) in dimyristoylphosphatidylcholine/cholesterol vesicles were studied, at 30 degrees C and 40 degrees C. The steady-state fluorescence intensity of both probes decreases markedly with increasing cholesterol concentration, unlike the fluorescence lifetimes. The liquid ordered to liquid disordered phase partition coefficients K(p) were measured, and values much less than unity were obtained for both probes, pointing to preference for the cholesterol-poor phase. Globally analyzed time-resolved energy transfer results confirmed these findings. It is concluded that, in particular, NBD-cholesterol is not a suitable cholesterol analog and its distribution behavior in phosphatidylcholine/cholesterol bilayers is in fact opposite to that of cholesterol. |
| Exclusion of candidate loci and cholesterol biosynthetic abnormalities in familial Pallister-Hall syndrome Biesecker, L. G., S. Kang, et al. (1996), J Med Genet 33(11): 947-51. Abstract: Pallister-Hall syndrome (PHS) was originally described in 1980 in six sporadic cases of children with structural anomalies including hypothalamic hamartoma, polydactyly, imperforate anus, and renal and pulmonary anomalies. In 1993, the first familial cases were reported, including affected sibs and vertical transmission. Three of these families are sufficiently large to allow initial evaluation by linkage studies to candidate genes or loci. We have evaluated candidate loci for PHS based on three clinical observations. The first is a patient with PHS-like malformations, including a hypothalamic hamartoma, and an unbalanced translocation involving 7q and 3p. The second is a family with familial PHS where the founder's father had an autosomal dominant hand malformation previously mapped to 17q. The third is the phenotypic overlap of PHS and Smith-Lemli-Opitz syndrome. In this report, we exclude these loci as candidates for linkage to the PHS phenotype on the basis of lod scores of less than-2.0. We conclude that hypothalamic hamartoma is not specific to PHS and that the dominant hand malformation in one of the families was a coincidence. To evaluate the relationship of PHS to Smith-Lemli-Opitz syndrome, we analysed levels of cholesterol and intermediate metabolites of the later stages of cholesterol biosynthesis. There is no evidence of a generalised disorder of cholesterol biosynthesis in patients with familial PHS. On genetic and biochemical grounds, we conclude that PHS and Smith-Lemli-Opitz syndrome are not allelic variants of a single locus. |
| Exclusive breast-feeding and weaning: effect on serum cholesterol and lipoprotein concentrations in infants during the first year of life Kallio, M. J., L. Salmenpera, et al. (1992), Pediatrics 89(4 Pt 1): 663-6. Abstract: The total serum cholesterol concentration of infants was investigated at birth (n = 193) and at the ages of 2 (n = 192), 4 (n = 192), 6 (n = 190), 9 (n = 188), and 12 months (n = 196). Concentrations of cholesterol--very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein-2 (HDL2), HDL3--and apoprotein B were analyzed in 36 infants at 2, 6, 9, and 12 months of age. Serum cholesterol concentration rose significantly more slowly in the weaned infants compared with exclusively breast-fed infants. The mean difference in total serum cholesterol value between the exclusively breast-fed and weaned infants was largest at ages 2 (0.9 mmol/L, P less than.001), 4 (0.6 mmol/L, P less than.01), and 6 months (0.5 mmol/L, P less than.01). The LDL cholesterol concentration was lower in weaned infants compared with exclusively breast-fed infants at age 2 and 6 months; the mean difference in LDL cholesterol value was 0.9 mmol/L at age 2 months (P less than.001) and 0.7 mmol/L at age 6 months (P less than.025). Also, the apoprotein B concentration was lower in weaned infants; the mean difference was 24 mg/dL at age 2 months (P less than.01) and 30 mg/dL at age 6 months (P less than.05). The apoprotein B-LDL cholesterol ratio was stable and similar in both feeding groups through the year. The HDL2 cholesterol concentration was lower in the formula-fed than in breast-fed infants at 2 months of age while the VLDL and HDL3 cholesterol concentrations were independent of the diet.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Exercise and dietary cholesterol alter rat myocardial capillary ultrastructure Cosmas, A. C., K. Kernan, et al. (1997), Eur J Appl Physiol Occup Physiol 75(1): 62-7. Abstract: The effects of a cholesterol-rich diet and exercise training on the myocardial capillary network and capillary ultrastructure were examined using Sprague-Dawley rats subjected to a 7-week exhaustive swimming scheme. A total of 16 animals were randomly divided into four groups consisting of normal dietinactive, normal dietexercise, cholesterol dietinactive, and cholesterol dietexercise. Following the experimental regimen the largest heart-mass-to-body-mass ratios were measured for the exercised rats fed a normal diet and the smallest ratios were found for the cholesterol-fed inactive rats. The capillary-to-fiber ratios and the capillary densities of the exercise-trained animals fed normal and cholesterol-containing diets were higher than those of either of the inactive groups. Diet and exercise had significant and opposing effects on the number of capillary pinocytotic vesicles and no significant effect on vesicle size. The capillary endothelium of the exercise-trained animal groups occupied a smaller proportion of the capillary area when compared to diet-matched inactive groups. The results of this study imply that exercise training and a cholesterol-containing diet have opposite effects on the heart-mass-to-body-mass ratio and capillary pinocytotic vesicle number. Furthermore, exercise increases the capillary network of the myocardium and may facilitate receptor-mediated transport in heart capillaries. |
| Exercise increases endothelin-1 plasma concentrations in patients with coronary artery disease: modulatory role of LDL cholesterol and of pentaerithrityltetranitrate Predel, H. G., H. Knigge, et al. (1995), J Cardiovasc Pharmacol 26 Suppl 3: S497-501. Abstract: Previous studies suggest that ET-1 plays a role in induction of coronary artery disease (CAD). It was shown that secretion of endothelin-1 (ET-1) by the vascular endothelium is enhanced in atherosclerotic alterations and may be antagonized by EDRF. The objective of the present study was to investigate the effects of ergometric exercise on plasma ET-1 concentrations, and the potential modulatory role of LDL cholesterol, and the effects of an orally administered nitrate, PETN, in patients with CAD. Ten men with CAD and 10 healthy men underwent bicycle ergometry according to the WHO-standards. Venous blood samples for determination of ET-1 concentrations were drawn directly before and 5 min after ergometric exercise. Patients were randomized and treated for 72 h in a crossover design either with placebo or pentaerithrityltetranitrate (PETN). After 72 h the identical ergometric protocol was repeated. Basal plasma levels of ET-1 were 6.1 +/- 0.7 pg/ml (patients) and 5.5 +/- 0.6 pg/ml (controls) (n.s.). After ergometric exercise ET-1 plasma concentrations rose significantly (7.3 +/- 0.9 pg/ml; p < 0.05) in the patient group under placebo treatment, whereas they remained constant (5.5 +/- 0.7 pg/ml) with PETN treatment. ET-1 levels remained unaffected by ergometric exercise in healthy controls. Mean LDL cholesterol plasma levels in patients with CAD were 156 +/- 8 mg% and 152 +/- 7 mg% in healthy controls. In the patient group there was a significant (p < 0.002) positive correlation between the exercise-induced increase in ET-1 and the LDL cholesterol plasma concentrations (r = 0.85). Blood pressure and heart rate were not modified by PETN treatment. In patients with CAD bicycle ergometry induced an increase in ET-1 plasma concentrations. The positive correlation with the LDL cholesterol plasma levels indicates that LDL cholesterol is involved in regulation of ET-1 secretion in vivo. PETN therapy completely abolished the exercise-induced increase in ET-1 plasma levels. This may result from local hemodynamic effects of the nitrate; hypothetically a nitrate-induced rise in the local NO concentrations can be considered. The clinical implications of these findings remain elusive. However, the findings of the present study are in accordance with the beneficial clinical effects of nitrates in patients with CAD. |
| Exercise might favor reverse cholesterol transport and lipoprotein clearance: potential mechanism for its anti-atherosclerotic effects Wei, C., M. Penumetcha, et al. (2005), Biochim Biophys Acta 1723(1-3): 124-7. Abstract: Livers of C57 BL/6 mice exercised for 2 weeks showed a dramatic increase in scavenger receptor B1 (SR-B1), CD36 and low density lipoprotein (LDL) receptor and a decrease in acetyl LDL receptor gene expression. These effects on lipoprotein receptors are reminiscent of the effects mediated by peroxisome proliferator-activated receptor (PPARgamma) ligands. |
| Exercise mitigates the association of abdominal obesity with high-density lipoprotein cholesterol in premenopausal women: results from the third National Health and Nutrition Examination Survey Heim, D. L., C. A. Holcomb, et al. (2000), J Am Diet Assoc 100(11): 1347-53. Abstract: OBJECTIVE: To examine the relationship between abdominal obesity, as measured by waist-to-hip ratio (WHR) and high-density lipoprotein cholesterol (HDL-C) level within the context of age, body fatness, exercise, saturated fat intake, and other plasma lipids. DESIGN/SUBJECTS: Subjects were premenopausal, white, non-Hispanic women from the third National Health and Nutrition Examination Survey. Smokers, heavy drinkers, and women who took lipid-altering drugs were excluded. Of 1,188 subjects who met the inclusion criteria, complete data were available for 435 women. STATISTICAL ANALYSES: Means were calculated using all subjects for each variable, then F-protected t tests and linear contrasts were performed to test differences in means between subgroups. A P <.05 was considered significant. RESULTS: Age was not significantly associated with HDL-C level. Comparisons of HDL-C by WHR, percentage body fat (%BF), and exercise level revealed that HDL-C level was significantly lower at the higher levels of WHR and %BF and higher at the highest levels of exercise. Higher levels of HDL-C were generally accompanied by lower levels of triacylglycerol. When HDL-C was compared by exercise level within each WHR tertile and %BF tertile, the association of exercise with HDL-C diminished. Saturated fat intake was not associated with HDL-C. CONCLUSIONS/APPLICATIONS: Increased exercise is associated with a lower WHR and subsequently a higher HDL-C level. This association between WHR and HDL-C appears to be mediated through %BF. Women exercisers with the highest WHR had consistently more favorable plasma lipid profiles and lower mean body mass index and %BF than nonexercisers. Thus, for women who exhibit abdominal obesity, exercise mitigates the association of WHR with HDL-C level. Vigorous exercise in the premenopausal years may promote a more favorable lipid profile, even in the presence of increased body fat and abdominal girth. |
| Exercise training has little effect on HDL levels and metabolism in men with initially low HDL cholesterol Zmuda, J. M., S. M. Yurgalevitch, et al. (1998), Atherosclerosis 137(1): 215-21. Abstract: Low concentrations of high-density lipoprotein cholesterol (HDL-C) are a recognized risk factor for atherosclerotic cardiovascular disease. Exercise is often recommended to increase HDL-C, but the effect of exercise training on HDL levels and metabolism in subjects with low HDL concentrations is not well defined. The present study compared the HDL response to 12 months of supervised endurance exercise training without weight loss in 17 men aged 26 49 years with initially low (< 40 mg/dl, N=7) or normal (> 44 mg/dl, N=10) HDL-C levels. HDL-C levels and HDL apolipoprotein metabolism were assessed while the subjects consumed controlled diets before and after the year of training. Increases in total (5.1+/-2.8 versus 1.9+/-4.2 mg/dl, P=0.08) and HDL2 (3.8+/-2.9 versus 0.4+/-1.1 mg/dl, P=0.01) cholesterol were greater in men with normal initial HDL-C levels. Catabolic rates for HDL apolipoproteins decreased 7-14% and biological half-lives increased 10-15% after exercise training in subjects with normal HDL, but were unchanged in the low HDL-C group. HDL apolipoprotein synthetic rates were not consistently affected by exercise training in either group. Postheparin lipoprotein lipase activity increased 27%, the clearance rate of intravenous triglycerides increased 14%, and apolipoprotein B levels decreased 16% with training in subjects with normal HDL-C but were unchanged in the low HDL-C group. We conclude that the ability to increase HDL-C levels through endurance exercise training is limited in subjects with low initial HDL-C, possibly because exercise training in such subjects fails to alter triglyceride metabolism. |
| Exercise-induced cholesterol depletion and Na+,K(+)-ATPase activities in human red cell membrane Shanmugasundaram, K. R., C. Padmavathi, et al. (1992), Exp Physiol 77(6): 933-6. Abstract: Red cell membranes were isolated from blood samples obtained from athletes during exhaustive exercise on a bicycle ergometer and during the subsequent recovery period of 60 min. Plasma lactate levels were also determined. During exercise, cell membranes were progressively depleted of cholesterol and, at exhaustion, membrane cholesterol was less than 80% of the initial level. A parallel decline in Na+,K(+)-ATPase was also noted, while phospholipid reduction was around 5%. During recovery, the erythrocyte membrane cholesterol and Na+,K(+)-ATPase increased, but at a slow rate and were inversely proportional to plasma lactate content. |
| Exercise-induced vasomotion of angiographically normal and stenotic coronary arteries improves after cholesterol-lowering drug therapy with bezafibrate Seiler, C., T. M. Suter, et al. (1995), J Am Coll Cardiol 26(7): 1615-22. Abstract: OBJECTIVES. We attempted to determine whether the coronary vasomotor response to exercise improves after cholesterol-lowering drug therapy with bezafibrate. BACKGROUND. Hypercholesterolemia and other coronary risk factors are associated with impaired endothelium-dependent coronary vasomotor response to physiologic or pharmacologic stimuli, even in the absence of overt coronary atherosclerosis. It is still unknown whether the coronary artery vasomotor response to dynamic exercise improves under cholesterol-lowering drug therapy. METHODS. Of 15 male patients (age 51 +/- 7 years mean +/- SD) included in the study, 7 had markedly elevated cholesterol levels (> or = 6.5 mmol/liter, therapy group), and 8 had normal or slightly elevated cholesterol levels (< 6.5 mmol/liter, control group). At baseline and after 7 months of cholesterol-lowering therapy with bezafibrate (400 mg/day) in the therapy group, coronary vasomotor response to dynamic exercise (percent change in cross-sectional vascular area at maximal exercise vs. rest 100%) in normal and stenotic, previously dilated vessels was assessed by quantitative coronary angiography. RESULTS. During follow-up, total serum cholesterol levels in the therapy group decreased from 7.8 +/- 1.1 to 5.8 +/- 1.1 mmol/liter (p = 0.0001) and did not change significantly in the control group (from 5.4 +/- 0.9 to 6.0 +/- 1.2 mmol/liter, p = NS). Exercise-induced vasomotor response (at similar work loads in the therapy and control groups) in both normal and dilated stenotic coronary arteries improved significantly in the therapy group, from 100 +/- 9% to 109 +/- 7% (p = 0.0001, cross-sectional area at rest 100%) and from 80 +/- 11% to 106 +/- 7% (p = 0.0002), respectively, but did not improve during follow-up in the control group. CONCLUSIONS. The present study indicates that cholesterol-lowering drug therapy with bezafibrate for 7 months improves exercise-induced vasomotion of angiographically normal coronary arteries. Seven months after coronary angioplasty, the reduction in serum cholesterol levels is, at least in part, associated with a restoration of the initially disturbed vasomotor response of stenotic vessel segments to exercise. |
| Existing and investigational combination drug therapy for high-density lipoprotein cholesterol Bays, H. (2002), Am J Cardiol 90(10B): 30K-43K. Abstract: For the past 3 to 4 decades, clinical outcomes trials have shown that drugs that favorably alter serum lipid levels reduce the risk of coronary artery disease (CAD) events. However, despite these successes, the reduction in serum low-density lipoprotein (LDL) cholesterol levels with monotherapy lipid-altering drugs does not "cure" CAD to the same degree that antibiotics "cure" many infections, nor do they "prevent" CAD in the same way that childhood immunizations "prevent" the onset of such conditions as measles, mumps, and rubella. Clinical outcome trials of monotherapy lipid-altering drugs have demonstrated a reduction in the relative risk of CAD in only a minority of patients. Thus, although safe and very effective in lowering serum LDL cholesterol levels, drugs that predominantly lower cholesterol do not "cure" atherosclerotic disease, nor have they been shown to "prevent" most CAD events in numerous clinical outcome trials. The reason for the suboptimal CAD outcomes benefits of monotherapy lipid-altering drugs is likely because atherosclerosis is a complex pathologic process with many important risk factors involved in the initiation and progression of atherosclerotic lesions and involved in the onset of the CAD event itself. An elevated serum LDL cholesterol level is an important CAD risk factor, but it is not the only lipid risk factor. A decreased serum high-density lipoprotein (HDL) cholesterol level is another important risk factor for CAD. Combination therapy through existing drugs (or possibly, in the future, through investigational lipid-altering drugs) may not only improve LDL cholesterol but also improve serum HDL cholesterol levels. This more global, multidimensional approach to lipid-altering drug treatment may provide the best chance to prevent CAD. |
| Exogenous cholesterol--initiated transmembrane signalling pathway regulates cholesterogenesis in human platelets Kaul, D. and J. Singh (1994), Cell Signal 6(2): 141-5. Abstract: Incubation of gel-filtered human platelets with cholesterol in the absence of divalent ions revealed that exogenous cholesterol had the ability to down-regulate the cholesterol biosynthesis in a dose-dependent fashion and this phenomenon was paralleled by an increase in phospholipase D activity. However, exogenous calcium in the presence of either cholesterol or phosphatidic acid had the capacity to up-regulate the platelet cholesterol synthesis in a dose-dependent manner. Further, cyclic nucleotides (cAMP, cGMP) also had the ability to influence directly the regulation of platelet cholesterol synthesis. Based upon these, as well as our earlier findings, we propose that exogenous cholesterol through its specific receptor regulates cholesterogenesis either directly or by initiating the transmembrane-signalling pathway involving cyclic nucleotides. |
| Exogenous glucocorticoids increase macrophage secretion of apo E by cholesterol-independent pathways Zuckerman, S. H., G. F. Evans, et al. (1993), Atherosclerosis 103(1): 43-54. Abstract: Macrophage apo E synthesis and secretion has been previously demonstrated to be regulated by intracellular free cholesterol levels and is decreased by cytokines and other inflammatory stimuli associated with macrophage activation. In a recent study, the opposing effects of TGF beta and GM-CSF were reported with the former increasing and the latter decreasing apo E secretion and apo E mRNA levels. In an attempt to further understand the mechanisms by which TGF beta increased apo E expression in mouse peritoneal macrophages, the present study was performed to determine whether pharmacological agents could up-regulate apo E secretion by a mechanism independent of intracellular free cholesterol levels. Agents which resulted in increased apo E secretion were subdivided based on their effects on cAMP elevation. In addition to TGF beta, dexamethasone resulted in significant increases in apo E secretion. The 2-4-fold enhancement in apo E secretion by both TGF beta and dexamethasone occurred without concomitant changes in intracellular cAMP or free cholesterol. Other agents which increased apo E secretion included cholera toxin and 8-bromo-cAMP. While these agents did not affect intracellular cholesterol levels, cholera toxin did increase macrophage cAMP. The changes in apo E secretion by dexamethasone and 8-bromo-cAMP were associated with elevations in apo E mRNA. Dexamethasone-treated macrophages had 6-fold increases in apo E mRNA by 48 h when compared with control macrophages. Macrophages stimulated with 8-bromo-cAMP for 48 h demonstrated a more modest but statistically significant (P < 0.001) 2.2-fold increase. Similar effects of dexamethasone, cholera toxin, TGF beta, and 8-bromo-cAMP on apo E secretion were also apparent in macrophage-derived foam cells. In addition to increasing apo E secretion in macrophages and foam cells, dexamethasone and 8-bromo-cAMP inhibited the down-regulation of apo E secretion mediated by LPS and GM-CSF. Finally, the increased apo E secretion by exogenous glucocorticoids or TGF beta was not species specific as similar effects were observed in rabbit peritoneal macrophages. Therefore, while macrophage activation results in decreased apo E synthesis, macrophages exposed to anti-inflammatory agents including dexamethasone, TGF beta, or following cAMP elevation demonstrate increased apo E secretion by a cholesterol-independent mechanism. |
| Exogenous hypercholesterolemic rats, compared with their progenitor, Sprague-Dawley rats, promptly alter cholesterol metabolism in the liver and secrete cholesterol-rich particles in response to dietary cholesterol Sakono, M., H. Mori, et al. (1996), Comp Biochem Physiol B Biochem Mol Biol 113(4): 803-8. Abstract: Early responses of cholesterol metabolism to dietary cholesterol were compared between exogenous hypercholesterolemic (ExHC) and Sprague-Dawley rats. Both strains had a similar radioactivity of 14Ccholesterol in the serum half a day after the oral administration, but thereafter the radioactivity disappeared slowly in ExHC rats. ExHC rats promptly altered in response to the dietary cholesterol, activities of cholesterol 7 alpha-hydroxylase and cholesterol synthesis in the liver and fecal excretion of bile acids derived from 14Ccholesterol administered orally. Lymphatic transport for 24 hr 14Ccholesterol was similar between the strains. Triton administration resulted in a marked accumulation of cholesterol in serum d > 1.006 g/mL lipoproteins in ExHC rats; in addition, the formation of cholesteryl esters from 14Coleic acid intravenously infused was greater in ExHC rats. These results indicate that ExHC rats increase serum cholesterol in response to exogenous cholesterol by decreasing the liver uptake and enhancing the secretion in the liver. |
| Exogenous supply of artificial lipoproteins does not decrease susceptibility to atherosclerosis in cholesterol-fed rabbits Mezdour, H., T. Yamamura, et al. (1995), Atherosclerosis 113(2): 237-46. Abstract: We investigated the effects of reconstituted apo A-I-containing high-density lipoprotein (r-HDL, homologous to small pre-beta-migrating HDL) and reconstituted triglyceride-rich lipoprotein (r-TRL, a mixture of Intralipid and apo E) on atherogenesis in rabbits fed a 0.5% cholesterol diet for 8 weeks. Male Japanese white rabbits (n = 17) were divided into three groups: the control group (n = 7) received a placebo and 2.5 ml of Intralipid 20 h later; the second group (n = 6) received r-HDL containing 18 mg of apo A-I followed by 2.5 ml of Intralipid; and the third group (n = 4) received 18 mg of r-HDL and 2.5 ml of r-TRL containing 4 mg of apo E. Rabbits were injected with the agents weekly and the same interval (20 h) was maintained between the two injections. Three minutes after the injection of r-HDL, a sharp increase in the pre-beta-migrating fraction was observed. The cholesterol-rich diet similarly increased serum lipids in the three groups. No significant changes of the HDL cholesterol and apo A-I concentrations were observed in the three groups. Conversely, there was a 12-fold increase of apo E which correlated positively with the total cholesterol level. Injection of r-HDL and r-TRL caused slight inhibition of fatty streak development and lipid deposition in the aortic wall, but neither change was statistically significant. Lipid accumulation in the liver was similar in all three groups. These results suggest that the physiological properties of artificial and native lipoproteins may differ. |
| Experimental determination and mathematical model of the transient incorporation of cholesterol in the arterial wall Neumann, S. J., S. A. Berceli, et al. (1990), Bull Math Biol 52(6): 711-32. Abstract: Experimental data of the radial incorporation of labeled cholesterol 14C-4 into the artery wall is regressed against a mathematical model that predicts macromolecular transport in this biological system. Data is obtained using excised canine carotid arteries that are perfused in vitro under pulsatile hemodynamic conditions for 2 hr. Vessels are exposed to either normotensive hemodynamics, hypertensive hemodynamics, or simulations in which the rate of flow or vessel compliance is deliberately altered. Several arteries are studied under normotensive conditions following balloon catheter deendothelialization. Transmural concentration profiles of 14C-4 activity are determined by microcryotomy of longitudinal sections of perfused vessels. Nonlinear Marquardt regression on 12 experimental cases yields parameter estimates of effective diffusivity, D and solute filtration velocity, V. Results of this experimental investigation support our hypothesis that hemodynamics and the endothelial lining influence wall flux in intact vessels. Exposure to altered (vs normotensive) hemodynamics is associated with increased incorporation of labeled cholesterol. A similar observation is made for deendothelialized vessels (e.g. a greater accumulation of label and a rise in convective flux). Based upon our companion measurements of vessel wall forces and endothelial cellular morphology accompanying hemodynamic simulations, we suggest that hemodynamically induced alterations to endothelial structures lead to the increased permeability, convection and incorporation that we observe in this work. |
| Experimental drug can double levels of "good" cholesterol. But does torcetrapib cut the risk of heart disease? Ornato, J. P. (2004), Health News 10(6): 13. |
| Experimental glomerulopathy alters renal cortical cholesterol, SR-B1, ABCA1, and HMG CoA reductase expression Johnson, A. C., J. M. Yabu, et al. (2003), Am J Pathol 162(1): 283-91. Abstract: Previous studies indicate that acute tubular injury causes free cholesterol (FC) and cholesteryl ester (CE) accumulation within renal cortex/proximal tubules. This study assessed whether similar changes occur with glomerulopathy/nephrotic syndrome, in which high-circulating/filtered lipoprotein levels increase renal cholesterol supply. Potential adaptive changes in cholesterol synthetic/transport proteins were also assessed. Nephrotoxic serum (NTS) or passive Heymann nephritis (PHN) was induced in Sprague-Dawley rats. Renal injury (blood urea nitrogen, proteinuria) was assessed 2 and 7 days (NTS), or 10 and 30 days (PHN) later. FC and CE levels in renal cortex, isolated glomeruli, and proximal tubule segments were determined. SR-B1 (a CE influx protein), ABCA1 (a FC exporter), and HMG CoA reductase protein/mRNA levels were also assessed. FC was minimally elevated in renal cortex (0 to 15%), the majority apparently localizing to proximal tubules. More dramatic CE elevations were found (approximately 5 to 15x), correlating with the severity of proteinuria at any single time point (r >/= 0.85). Cholesterol increments were associated with decreased SR-B1, increased ABCA1, and increased HMG CoA reductase (HMGCR) protein and its mRNA. Tubule (HK-2) cell culture data indicated that SR-B1 and ABCA1 levels are responsive to cholesterol supply. Experimental nephropathy can increase renal FC, and particularly CE, levels, most notably in proximal tubules. These changes are associated with adaptations in SR-B1 and ABCA1 expression, which are physiologically appropriate changes for a cholesterol overload state. However, HMGCR protein/mRNA increments can also result. These seem to reflect a maladaptive response, potentially contributing to a cell cholesterol overload state. |