| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Elimination of cholesterol as cholestenoic acid in human lung by sterol 27-hydroxylase: evidence that most of this steroid in the circulation is of pulmonary origin Babiker, A., O. Andersson, et al. (1999), J Lipid Res 40(8): 1417-25. Abstract: Human alveolar macrophages have exceptionally high capacity to convert cholesterol into 27-hydroxycholesterol and cholestenoic acid by the sterol 27-hydroxylase mechanism. It is shown here that the human lung has a higher content of 27-hydroxycholesterol relative to cholesterol than any other organ. In order to evaluate the importance of the sterol 27-hydroxylase mechanism for cholesterol homeostasis in the lung, the production of cholestenoic acid by human lung was investigated. Removal of one lung reduced the level of cholestenoic acid in the circulation by 48 +/- 4% (P < 0.005). The levels of cholestenoic acid in the pulmonary artery and in the pulmonary vein showed significant differences (P < 0.002) with higher levels in the pulmonary vein (108 +/- 16 and 104 +/- 16 ng/mL, respectively). This corresponds to a net flux of cholestenoic acid from the lung of about 14 mg/day, which is more than 80% of the reported removal of this oxysterol and its metabolites from the circulation by the liver per day. Bypassing the lung for 60 min led to a reduction in circulating cholestenoic acid (30%) that fits with a pulmonary origin when taking into account the half-life of cholestenoic acid. The level of circulating cholestenoic acid was found to be less in patients with different lung diseases. It is evident that most of the cholestenoic acid in the circulation is of pulmonary origin. The present results suggest that the sterol 27-hydroxylase in the lung is responsible for at least half of the total flux of 27-oxygenated cholesterol metabolites to the liver and that this enzyme system may be of importance for cholesterol homeostasis in the lung. |
| Elimination of cholesterol ester from macrophage foam cells by adenovirus-mediated gene transfer of hormone-sensitive lipase Okazaki, H., J. Osuga, et al. (2002), J Biol Chem 277(35): 31893-9. Abstract: Cholesterol ester (CE)-laden foam cells are a hallmark of atherosclerosis. To determine whether stimulation of the hydrolysis of cytosolic CE can be used as a novel therapeutic modality of atherosclerosis, we overexpressed hormone-sensitive lipase (HSL) in THP-1 macrophage-like cells by adenovirus-mediated gene delivery, and we examined its effects on the cellular cholesterol trafficking. We show here that the overexpression of HSL robustly increased neutral CE hydrolase activity and completely eliminated CE in the cells that had been preloaded with CE by incubation with acetylated low density lipoprotein. In these cells, cholesterol efflux was stimulated in the absence or presence of high density lipoproteins, which might be at least partially explained by the increase in the expression of ABCA1. Importantly, these effects were achieved without the addition of acyl-CoA:cholesterol acyltransferase inhibitor, cAMP, or even high density lipoproteins. Furthermore, the uptake and degradation of acetylated low density lipoprotein was significantly reduced probably by decreased expression of scavenger receptor A and CD36. Notably, the cells with stimulated CE hydrolysis did not exhibit either buildup of free cholesterol or cytotoxicity. In conclusion, increased hydrolysis of CE by the overexpression of HSL leads to complete elimination of CE from THP-1 foam cells not only by increasing efflux but also by decreasing influx of cholesterol. |
| Elimination of cholesterol in human endothelial cells Xiu, R., C. Duan, et al. (1997), Zhonghua Yi Xue Za Zhi 77(9): 676-9. Abstract: OBJECTIVE: To investigate what role the endothelial cell interfacing with blood components to play in cholesterol metabolism. METHODS: Isotopelabeling technique, Gas Chromatography/Mass Spectrometry and Western blotting were used to measure the presence of 27-oxygenated cholesterol in medium and the presence of sterol 27-hydroxylase in endothelium. RESULTS: When human endothelial cells were cultured in a medium containing fetal calf serum, there was a significant accumulation of 27-hydroxycholesterol and 3 beta-hydroxy-5-cholesteneic acid, products of cholesterol metabolism, in the medium. The rate of formation of these products almost increased linearly with time of cultivation. After addition of 100 micrograms of extraneous cholesterol to the medium, the accumulation of 27-hydroxy-cholesterol and 3 beta-hydroxy-5-cholesteneic acid increased significantly. Addition of more cholesterol did not further increase the formation of 27-hydroxy-cholesterol and caused a decrease in the formation of 3 beta-hydroxy-5 cholesteneic acid. The presence of sterol-27-hydroxylase in the endothelium was demonstrated by Western blotting. CONCLUSION: Cultured human endothelium from umbilical veins are able to convert exogenous cholesterol into 27-hydroxy-cholesterol and 3 beta-hydroxy-5-cholesteneic acid. Furthermore, the cells are able to transport these products from the cells into the medium. |
| Elimination of cholesterol in macrophages and endothelial cells by the sterol 27-hydroxylase mechanism. Comparison with high density lipoprotein-mediated reverse cholesterol transport Babiker, A., O. Andersson, et al. (1997), J Biol Chem 272(42): 26253-61. Abstract: Cultured macrophages and endothelial cells have been reported to secrete 27-oxygenated metabolites of cholesterol. This mechanism was compared with the classical high density lipoprotein (HDL)-dependent reverse cholesterol transport. Under standard conditions, macrophage preparations had considerably higher capacity to secrete 27-hydroxycholesterol and 3beta-hydroxy-5-cholestenoic acid than had endothelial cells and fibroblasts. Western blotting showed that lung macrophages contained the most sterol 27-hydroxylase protein of the cells tested. The relative amounts of 3beta-hydroxy-5-cholestenoic acid produced by the macrophages were also highest. Macrophages derived from monocytes of patients with sterol 27-hydroxylase deficiency did not secrete 27-oxygenated products, demonstrating that sterol 27-hydroxylase is the critical enzyme for the conversion of cholesterol into the 27-oxygenated steroids. That sterol 27-hydroxylase is responsible not only for 27-hydroxylation of cholesterol but also for the further oxidation of this steroid into 3beta-hydroxy-5-cholestenoic acid was shown with use of tritium-labeled 27-hydroxycholesterol and an inhibitor of sterol 27-hydroxylase. Secretion of 27-oxygenated products by the cultured macrophages as well as the ratio between the alcohol and the acid appeared to be dependent upon total 27-hydroxylase activity, the availability of substrate cholesterol, and the presence of an acceptor for 27-hydroxycholesterol in the medium. With albumin as extracellular acceptor, the major secreted product was 3beta-hydroxy-5-cholestenoic acid. Under such conditions, secretion of labeled 27-oxygenated products was higher than that of labeled cholesterol from lung alveolar macrophages preloaded with 4-14Ccholesterol. With HDL as acceptor, 27-hydroxycholesterol was the major secreted product, and the total secretion of labeled 27-oxygenated products was only about 10% of that of labeled cholesterol. Thus, 27-hydroxycholesterol and cholesterol may compete for HDL-mediated efflux from the cells. The results support the contention that the sterol 27-hydroxylase-mediated elimination of cholesterol is more important in macrophages than in endothelial cells. This mechanism may be an alternative and/or a complement to the classical HDL-mediated reverse cholesterol transport in macrophages, in particular when the concentration of HDL is low. |
| Embolism caused by cholesterol Godeau, P., M. Vayssairat, et al. (1991), J Mal Vasc 16(1): 58-66. |
| Embolism due to cholesterol crystals Perez Villoria, J., J. M. Ayuela Azcarate, et al. (1993), Rev Esp Cardiol 46(3): 205-8. Abstract: We present a case of cholesterol crystal embolization confirmed histologically by skin biopsy and by the presence of a yellowish microemboli with a refringent look lodged inside a retinal arterioles. The presence of a typical clinic case history, together concurrent risk factor (coronarography, implantation of stent and anticoagulation) supported the diagnostic suspicion. Although it is a serious illness, often with a fatal evolution, the patient has followed a favourable clinic course. |
| Embolisms of cholesterol crystals and their digestive manifestations Levecq, H., J. Barge, et al. (1992), Ann Gastroenterol Hepatol (Paris) 28(1): 7-11. Abstract: We report a case of cholesterol crystal embolization associated with secretory diarrhea, megacolon and acalculous cholecystitis. Cholesterol emboli were found within the submucosal arterioles of the small and large bowel as well as in the gallbladder wall. Cholesterol crystal embolization is an often unrecognized disease, occurring in elderly patients with severe atherosclerosis. Cholesterol emboli may induce misleading gastrointestinal manifestations with both hemorrhagic and ischemic lesions. Though an uncommon symptom in this setting, secretory diarrhea did not seem to be fortuitous and could have been also a consequence of cholesterol crystal embolization. |
| Embryonic striatal neurons from niemann-pick type C mice exhibit defects in cholesterol metabolism and neurotrophin responsiveness Henderson, L. P., L. Lin, et al. (2000), J Biol Chem 275(26): 20179-87. Abstract: Niemann-Pick type C (NP-C) disease is a progressive and fatal neuropathological disorder previously characterized by abnormal cholesterol metabolism in peripheral tissues. Although a defective gene has been identified in both humans and the npc(nih) mouse model of NP-C disease, how this leads to abnormal neuronal function is unclear. Here we show that whereas embryonic striatal neurons from npc(nih) mice can take up low density lipoprotein-derived cholesterol, its subsequent hydrolysis and esterification are significantly reduced. Given the importance of cholesterol to a variety of signal transduction mechanisms, we assessed the effect of this abnormality on the ability of these neurons to respond to brain-derived neurotrophic factor (BDNF). In contrast to its effects on wild type neurons, BDNF failed to induce autophosphorylation of the TrkB receptor and to increase neurite outgrowth in npc(nih) neurons, despite expression of TrkB on the cell surface. The results suggest that abnormal cholesterol metabolism occurs in neurons in the brain during NP-C disease, even at embryonic stages of development prior to the onset of phenotypic symptoms. Moreover, this defect is associated with a lack of TrkB function and BDNF responsiveness, which may contribute to the loss of neuronal function observed in NP-C disease. |
| Emerging importance of HDL cholesterol in developing high-risk coronary plaques in acute coronary syndromes Viles-Gonzalez, J. F., V. Fuster, et al. (2003), Curr Opin Cardiol 18(4): 286-94. Abstract: Cardiovascular disease is the principal cause of death in industrialized countries. Hyperlipidemia, with high low-density lipoprotein cholesterol and triglycerides, and low high-density lipoprotein cholesterol levels (<40 mg/dL in men and <45 mg/dL in women), is a known major cardiovascular risk factor. Statins are considered the most potent and effective agents to reduce low-density lipoprotein cholesterol, but they have a variable effect on high-density lipoprotein cholesterol and triglycerides. Different clinical trials with statins have shown a decrease in low-density lipoprotein cholesterol by 35% and a reduction of the incidence of coronary events by as much as 30%. However, 60 to 70% of events still occur, despite remarkable reduction of low-density lipoprotein cholesterol concentration. Recent National Cholesterol Education Program guidelines highlighted the importance of high-density lipoprotein cholesterol concentration in the prevention and treatment of cardiovascular disease. High-density lipoprotein cholesterol is considered an independent risk factor and has an inverse relation with coronary events. The association of low levels of high-density lipoprotein cholesterol with an increased incidence of cardiovascular events implies a critical role of high-density lipoprotein in the protection against atherosclerotic disease and in the progression of coronary atherosclerotic disease. High-density lipoprotein cholesterol appears to exert this protective effect through multiple mechanisms. High-density lipoprotein is not only involved in reverse cholesterol transport, but also prevents endothelial dysfunction; inhibits the homing of monocytes, apoptosis, platelet activation, and factor X activation; and has antioxidant properties. In this article the authors review the available experimental and clinical evidence supporting the importance of high-density lipoprotein cholesterol as a protective factor in coronary artery disease, and the strategies developed to increase high-density lipoprotein cholesterol. |
| Emphasis on high-density lipoprotein cholesterol in patients with coronary artery disease Mailander, L., C. J. Lavie, et al. (1993), South Med J 86(5): 508-12. Abstract: Although numerous epidemiologic and lipid intervention studies clearly demonstrate the pivotal role of high-density lipoprotein cholesterol (HDL-C) on risk of coronary artery disease (CAD), the National Cholesterol Education Program (NCEP) has emphasized only total cholesterol and low-density lipoprotein cholesterol (LDL-C), and has underemphasized the role of HDL-C in their lipid assessment and treatment recommendations. In a review of 113 consecutive patients in our cardiac rehabilitation program, lipid levels improved modestly with cardiac rehabilitation. "Ideal" lipids (LDL-C < 130 mg/dL according to the NCEP) were present in 49% before the rehabilitation program and in 46% afterward. In fact, 60 (53%) of our patients had total cholesterol levels < 200 mg/dL and would require no further lipid assessment or treatment according to the NCEP. Of these 60 patients, 40 (67%) had low HDL-C (< or = 35 mg/dL). In our total study group, 56% (63/113) had HDL-C < or = 35 mg/dL and 33% (37/113) had HDL-C < or = 30 mg/dL before rehabilitation (compared to 42% and 21%, respectively, after rehabilitation. On the other hand, a "high-risk" LDL-C value (> or = 160 mg/dL) was found in only 17% of patients at baseline and in only 13% after the cardiac rehabilitation program. Using an approach that incorporates the pivotal role of both LDL-C and HDL-C (LDL-C > or = 160 mg/dL or HDL-C < or = 35 mg/dL) for our patients with known CAD, 65% would require drug treatment before rehabilitation and 53% after rehabilitation. We conclude that: (1) lipids improve only modestly (though the change is significant statistically) with cardiac rehabilitation; (2) low levels of HDL-C are prevalent in cardiac rehabilitation patients and are much more prevalent than elevated LDL-C, both before and after rehabilitation; and (3) the NCEP should reevaluate the pivotal role of HDL-C in its assessment and treatment guidelines, particularly in patients with known CAD, since emphasis on both LDL-C and HDL-C is needed for optimal primary and secondary prevention of CAD. |
| Enantiospecificity of cholesterol function in vivo Crowder, C. M., E. J. Westover, et al. (2001), J Biol Chem 276(48): 44369-72. Abstract: The importance of the absolute configuration of cholesterol for its function in vivo is unknown. To directly test this question in vivo, we synthesized the enantiomer of cholesterol (ent-cholesterol) and tested its ability to substitute for natural cholesterol (nat-cholesterol) in the growth, viability, and behavior of Caenorhabditis elegans, a cholesterol auxotroph. First-generation animals grown on ent-cholesterol were viable with only mild behavioral defects. However, ent-cholesterol produced 100% lethality/arrest of their second generation progeny. Isotopically labeled ent-cholesterol incorporated into animals, indicating that its lethality was not secondary to cholesterol starvation. When mixed with nat-cholesterol, ent-cholesterol was not inert; rather, it antagonized the activity of nat-cholesterol. These results demonstrate for the first time that the absolute configuration of cholesterol, not just its physical properties, is essential for its functions in vivo. |
| Encapsulation characteristics of nystatin in liposomes: effects of cholesterol and polyethylene glycol derivatives Moribe, K., K. Maruyama, et al. (1999), Int J Pharm 188(2): 193-202. Abstract: In this study, we characterized the encapsulation of amphipathic nystatin into liposomes with or without cholesterol (CH) and a polyethylene glycol derivative, distearoyl-N-(monomethoxy poly(ethylene glycol)succinyl)phosphatidylethanolamine (DSPE-PEG). The highest encapsulation efficacy of nystatin into liposomes (151 microg nystatin/mg lipid) was obtained with a cholesterol-free lipid composition containing 6 mol% of DSPE-PEG. The encapsulation efficacy was decreased by the incorporation of CH and improved by the incorporation of DSPE-PEG. In liposomes composed of dipalmitoylphosphatidylcholine (DPPC)/CH (2:1, mol/mol), the highest encapsulation efficacy of nystatin liposomes (84 microg/mg lipid) was achieved by the addition of DSPE-PEG and hydration with 9% sucrose solution, as compared with 13 microg/mg lipid without DSPE-PEG. The encapsulated amount increased with increasing amount of DSPE-PEG used and plateaued at 6 mol% of DSPE-PEG. The optimum molecular weight of PEG in DSPE-PEG was 2000 and a larger molecular weight resulted in lower encapsulation. The incorporation of CH affected the self-association of nystatin with lipid membranes, which was detected by fluorescence measurement. The molecular interaction between an amino group in nystatin and a phosphate group in DSPE-PEG plays an important role in efficient encapsulation of nystatin. Finally, the encapsulation characteristics of nystatin were compared with those of amphotericin B (AmB). Nystatin more readily associated with CH-free lipid membranes, but, AmB more readily interacted with DSPE-PEG. The results indicated that the differences in the molecular association of AmB or nystatin with lipids or DSPE-PEG are reflected in the encapsulation characteristics in liposomes. |
| End of the coffee mystery: diterpene alcohols raise serum low-density lipoprotein cholesterol and triglyceride levels Heckers, H., U. Gobel, et al. (1994), J Intern Med 235(2): 192-3. |
| Endogenous apolipoprotein E modulates cholesterol efflux and cholesteryl ester hydrolysis mediated by high-density lipoprotein-3 and lipid-free apolipoproteins in mouse peritoneal macrophages Langer, C., Y. Huang, et al. (2000), J Mol Med 78(4): 217-27. Abstract: We investigated the effect of endogenous apolipoprotein (apo) E synthesis in mouse peritoneal macrophages on cholesterol efflux and intracellular cholesteryl ester hydrolysis mediated by high-density lipoprotein-3 (HDL3) and lipid-free apolipoproteins (apo). After loading with acetylated LDL (acLDL) peritoneal macrophages from wild-type (apoE(+/+)) and apoE-deficient (apoE(-/-)) mice were incubated with medium alone or with liposomes, HDL3, lipid-free apoA-I, or lipid-free apoE3. Cholesterol and cholesteryl esters in the cells and culture media were quantified by HPLC. Incubation of apoE(+/+) or apoE(-/-) macrophages for 18 h with medium alone or with liposomes did not cause significant changes in cellular cholesterol. Addition of HDL3, apoA-I, or apoE3 to the medium led to significant cholesterol efflux, which was less efficient in apoE(-/-) macrophages than in apoE(+/+) macrophages. HDL and lipid-free apolipoproteins were more effective in reducing the cellular content of cholesteryl esters of apoE(+/+) macrophages than of apoE(-/-) macrophages, suggesting that endogenous apoE stimulates cholesteryl ester hydrolysis. The difference in the mass of cholesteryl esters was more pronounced for cholesteryl arachidonate and linoleate than for cholesteryl oleate or palmitate. Furthermore, in (14)Carachidonate labeling experiments cholesterol arachidonate hydrolysis was higher in apoE(+/+) macrophages than in apoE(-/-) macrophages in the presence of cholesterol efflux mediated by HDL3 or apoA-I. In contrast, in the absence of cholesterol efflux cholesterol arachidonate synthesis was higher in apoE(+/+) macrophages than in apoE-/- macrophages. Taken together, our data suggest that endogenous apoE stimulates cholesterol efflux and intracellular cholesteryl ester hydrolysis mediated by HDL3 and lipid-free apolipoproteins in mouse peritoneal macrophages. This may contribute to the antiatherogenic effect of apoE. |
| Endogenous cholesterol synthesis is associated with VLDL-2 apoB-100 production in healthy humans Prinsen, B. H., J. A. Romijn, et al. (2003), J Lipid Res 44(7): 1341-8. Abstract: Subjects with high plasma cholesterol levels exhibit a high production of VLDL apolipoprotein B-100 (apoB-100), suggesting that cholesterol is a mediator for VLDL production. The objective of the study was to examine whether endogenous cholesterol synthesis, reflected by the lathosterol-cholesterol ratio (L-C ratio), affects the secretory rates of different VLDL subfractions. Ten healthy subjects were studied after overnight fasting. During a 10 h primed, constant infusion of 13C-valine (15 micromol/kg/h), enrichment was determined in apoB-100 from ultracentrifugally isolated VLDL-1 and VLDL-2 by gas chromatography mass spectrometry. The synthesis rates of VLDL-1 apoB-100 and VLDL-2 apoB-100, catabolism, and transfer were estimated by compartmental analysis. Mean VLDL-1 apoB-100 pool size was 90 +/- 15 mg, and mean VLDL-2 apoB-100 pool size was 111 +/- 14 mg. Absolute synthesis rate of VLDL-1 apoB-100 was 649 +/- 127 mg/day and 353 +/- 59 mg/day for VLDL-2 apoB-100. There was a strong association between the absolute synthesis rate of VLDL-2 apoB-100 and L-C ratio (r 2 = 0.61, P < 0.01). In contrast, no correlation was observed between L-C ratio and absolute synthesis rate of VLDL-1 apoB-100 (r 2 = 0.302, P = 0.09). In conclusion, these data provide additional support for an independent regulation of VLDL-1 apoB-100 and VLDL-2 apoB-100 production.Endogenous cholesterol synthesis is correlated only with the VLDL-2 apoB-100 production. |
| Endogenous neutralizing antibodies against platelet-derived growth factor-aa inhibit atherogenesis in the cholesterol-fed rabbit Lamb, D. J., T. Y. Avades, et al. (2001), Arterioscler Thromb Vasc Biol 21(6): 997-1003. Abstract: Previous studies have shown that the B chain of platelet-derived growth factor (PDGF) has an important role in atherogenesis. In this study we have investigated the contribution of PDGF-A chain in cholesterol-induced atherogenesis in the New Zealand White rabbit. High titers of antibodies to PDGF-AA or to platelet cytosolic protein (PCP) were induced in these animals by immunization against recombinant human PDGF-AA or human PCP. Rabbits were then fed a 0.25% to 1% cholesterol-containing diet for 10 weeks to induce atherosclerotic lesions; the rabbits were then humanely killed and perfusion-fixed and their aortas were removed. The extent of atherosclerosis in the thoracic aortas was determined by quantitative morphometry after staining with oil red O. The intimal and medial areas in histological sections taken at the level of the first intercostal branch were quantified by image analysis. Immunization against PDGF-AA and PCP, but not against adjuvant alone, resulted in rising titers of antibodies within 2 weeks, the levels of which reached a plateau by 8 weeks. The antibodies to PDGF-AA were isoform-specific, recognized both human and rabbit PDGF-AA, and neutralized the biological activity of PDGF-AA in vitro. Integrated plasma cholesterol levels were similar in both groups. Compared with nonimmune rabbits (n=10), animals immunized against PDGF-AA (n=10) or PCP (n=10) had significantly smaller areas of the aorta covered by atherosclerotic lesions (24.6+/-5.1% and 18.7+/-4.2%, respectively, vs 34.4+/-4.3%; P<0.05). This was associated with a reduced aortic intimal-medial area ratio in PDGF-AA-immunized (0.009+/-0.006) and PCP-immunized (0.025+/-0.017) rabbits than in nonimmune animals (0.159+/-0.066; P<0.05). These data suggest that PDGF-AA is actively involved in cholesterol-induced atherosclerosis in the rabbit. |
| Endogenous sex hormones and cholesterol gallstones: a case-control study in an echographic survey of gallstones Russo, F., A. Cavallini, et al. (1993), Am J Gastroenterol 88(5): 712-7. Abstract: In a population survey of gallstones, the serum levels of hormones of the pituitary-gonadal axis and the sex hormone-binding globulin (SHBG) were compared in subjects with cholesterol gallstones and in a control group. In 84 subjects who entered the survey, echographic gallstones that had been identified at the survey, turned out to be radiolucent or mixed (predominantly of cholesterol) at subsequent x-ray. The controls were without gallstones at echography, matched to the cases for potential confounders of the association sex hormones-cholelithiasis. Testosterone (T) 17-beta-estradiol (E2), 17-OH progesterone (P), and SHBG were dosed by radioimmunoassay; follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (Prl) by dissociation-enhanced lanthanide fluoro immunoassay (DELFIA). Men with gallstones had lower LH than controls (n = 34, median difference = -0.62 mU/ml, 95% confidence interval (CI) -1.20 to -0.26 mU/ml, paired sign test, p = 0.003). Premenopausal women in the luteal phase of the menstrual cycle with gallstones had higher E2 than controls (n = 7, median difference: +117, pg/ml, 95% CI: +10 to +218 pg/ml, p = 0.008). Postmenopausal women had lower LH than controls (n = 35, median difference = -4.57 mU/ml, 95% CI -9.5 to -1.0 mU/ml, p = 0.04). No other hormones showed statistically significant differences between cases and controls, in either males or females. The findings of this exploratory study in subjects with radiolucent and mixed gallstones suggest that men and postmenopausal women have lower LH, and premenopausal women in the luteal phase of the cycle have higher E2, than controls. |
| Endogenous sex hormones, high density lipoprotein cholesterol, and other lipoprotein fractions in men Khaw, K. T. and E. Barrett-Connor (1991), Arterioscler Thromb 11(3): 489-94. Abstract: At least some of the large preponderance for coronary heart disease in men has been attributed to differences in lipid and lipoprotein levels; notably, high density lipoprotein cholesterol (HDL-C), a protective factor, is higher in women. The sex differences in lipid levels have been postulated to be related to differences in sex hormones. In a southern California cohort of 391 men aged 30-79 years, HDL-C levels were positively correlated and very low density lipoprotein cholesterol (VLDL-C) levels were inversely correlated with testosterone levels independently of age, body mass index, physical exercise, smoking, and alcohol intake. Mean HDL-C levels were 12% higher and VLDL-C levels were 40% lower in the highest compared with the lowest quartile of testosterone level. Low density lipoprotein cholesterol levels were positively related to estrone, estradiol, and androstenedione levels. It is premature to attribute the sex differential in lipid cardiovascular risk profiles to higher levels of testosterone per se in men, since testosterone levels are favorably associated with cardiovascular risk while estrogen levels have the converse relation in men. The differing effects and interactions of specific endogenous sex hormones in men and women require further elucidation. |
| Endogenously elicited antibodies to platelet derived growth factor-BB and platelet cytosolic protein inhibit aortic lesion development in the cholesterol-fed rabbit Rutherford, C., W. Martin, et al. (1997), Int J Exp Pathol 78(1): 21-32. Abstract: Several studies have indicated that growth factors, such as platelet derived growth factor (PDGF), may be important in atherogenesis. These factors are released from platelets, or expressed by cells of the arterial wall. In order to study their role in atherogenesis more directly, rabbits were immunized with PDGF-BB, platelet cytosolic protein, or human serum albumin (HSA), until high titres of antibody were attained. Atherosclerotic lesions were subsequently induced by feeding the animals with a 2% cholesterol enriched diet. At the end of approximately 3 months, the extent of aortic lesion development was assessed by image analysis of en face preparations of aortae stained with Oil Red-O, and histological segments of aortae taken at the level of the first intercostal artery branch point. The endogenous antibodies were characterized with respect to their cross-reactivity, and ability to neutralize PDGF and platelet cytosol-induced cell proliferation and migration in vitro. The endogenous, anti-PDGF-BB antibody was isoform specific, and neutralized the mitogenic and chemotactic properties of PDGF-BB and rabbit platelet cytosolic protein in vitro. The anti-platelet cytosol antibody partially inhibited the chemotactic and mitogenic properties of rabbit platelet cytosolic protein. Compared to non-immune rabbits (n = 5), animals immunized with HSA (n = 4) had a significantly larger area of aortic lesion involvement (P < 0.01), whereas aortic lesions in rabbits immunized with PDGF-BB (n = 5), or platelet cytosolic protein (n = 7) were significantly smaller than either non-immune animals, or animals immunized with HSA (P < 0.05). The same pattern was observed for other measures of aortic lesion involvement including aortic intima:media ratio at the level of the first intercostal artery. These data suggest that PDGF-BB, and possibly other platelet-associated growth factors, are involved in cholesterol-induced atherosclerosis. |
| Endoscopic approach to orbitofrontal cholesterol granuloma Selva, D. and C. Chen (2004), Orbit 23(1): 49-52. Abstract: A 54-year-old man presented with an orbitofrontal cholesterol granuloma arising in the left frontal bone and abutting the dura. The lesion was successfully removed with an anterior orbitotomy via a superior lid crease incision. A 70-degree rigid endoscope was used to visualize removal of the granuloma from the inner surface of frontal bone and the dura. The patient made an uncomplicated recovery and there was no recurrence at two years follow-up. A combined anterior orbital and endoscopic approach may be an alternative to either frontal craniotomy or lateral orbitotomy in selected cases of orbitofrontal cholesterol granuloma. |