| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
| First Page | Previous Page | Next Page | Last Page |
| Cholesterol efflux regulatory protein, Tangier disease and familial high-density lipoprotein deficiency Hayden, M. R., S. M. Clee, et al. (2000), Curr Opin Lipidol 11(2): 117-22. Abstract: Cellular cholesterol efflux, by which cholesterol is transported from peripheral cells to HDL acceptor molecules for transport to the liver, is the first step of reverse cholesterol transport. Two genetic disorders, Tangier disease and some cases of familial HDL deficiency, have defects of cellular cholesterol efflux. The recent discovery of mutations in the ABC1 gene, which encodes the cholesterol efflux regulatory protein, in both these disorders establishes cholesterol efflux regulatory protein as a rate-limiting factor in reverse cholesterol transport. |
| Cholesterol efflux to apolipoprotein AI involves endocytosis and resecretion in a calcium-dependent pathway Takahashi, Y. and J. D. Smith (1999), Proc Natl Acad Sci U S A 96(20): 11358-63. Abstract: We previously have described the cAMP-mediated induction of cholesterol and phospholipid efflux from the murine macrophage RAW264 cell line to lipid-free apolipoprotein acceptors. This induction of cholesterol efflux is associated with increased binding and association of apolipoprotein to the cells. In the present study, using primarily apolipoprotein AI (apoAI) as the acceptor, cAMP-dependent cholesterol efflux to apolipoprotein acceptors was associated with apoAI binding to coated pits, cellular uptake, and resecretion. After cell association and washing, 58% of the apoAI was resecreted during a 90-min chase period. In addition, after apoAI uptake and washing, cholesterol efflux was observed during a chase period without additional acceptors. Cholesterol efflux was partially blocked by chlorpromazine and hypertonic media, two inhibitors of coated pit endocytosis. Cholesterol efflux to apoAI was found to depend on extracellular calcium. By temporally separating the cAMP induction phase from the apoAI chase phase, calcium was found to be required during the apoAI chase phase rather than during the cAMP induction period. In the absence of calcium the 8-Br-cAMP-mediated induction of apoAI binding was maintained, but the specific apoAI cellular association was inhibited. The data are consistent with a model for cholesterol efflux to apolipoproteins that involves a calcium-dependent endocytic pathway, followed by recycling and the subsequent release of the nascent lipoprotein particle from the cell. |
| Cholesterol efflux to high-density lipoproteins and apolipoprotein A-I phosphatidylcholine complexes is inhibited by ethanol: role of apolipoprotein structure and cooperative interaction of phosphatidylcholine and cholesterol Avdulov, N. A., S. V. Chochina, et al. (2000), Biochemistry 39(34): 10599-606. Abstract: There is a substantial body of evidence showing that moderate alcohol consumption is associated with a reduced risk of cardiovascular morbidity and mortality. One of the factors thought to contribute to this reduction in risk is an increase in the level of high-density lipoproteins (HDL) correlated with alcohol consumption. However, HDL levels are elevated in heavy drinkers, but their risk of vascular disease is greater compared with that of moderate drinkers. Ethanol at concentrations observed in heavy drinkers and alcoholics may directly act on HDL and apolipoproteins and in turn modify cholesterol efflux. In this paper, we show that ethanol significantly inhibited cholesterol efflux from fibroblasts to HDL and to apolipoprotein A-I (apoA-I) complexed with phosphatidylcholine (PC). Ethanol significantly inhibited binding of PC to apoA-I, inhibited incorporation of cholesterol only when apoA-I contained PC, and did not alter incorporation of cholesterol into HDL. ApoA-I structure was altered by ethanol as monitored by steady-state fluorescence polarization of tryptophan residues. The absence of ethanol effects on incorporation of cholesterol into HDL versus inhibition of cholesterol incorporation into the apoA-I-PC complex suggests that the effects of ethanol on cholesterol efflux mediated by HDL involve interaction with the cell surface and that efflux mediated by the apoA-I-PC complex is a combination of aqueous diffusion and contact with the cell surface. In addition, effects of ethanol on apoA-I suggest that pre-beta-HDL or lipid-free apoA-I may be more perturbed by ethanol than mature HDL, and such effects may be pathophysiological with respect to the process of reverse cholesterol transport in heavy drinkers and alcoholics. |
| Cholesterol efflux, cholesterol esterification, and cholesteryl ester transfer by LpA-I and LpA-I/A-II in native plasma Huang, Y., A. von Eckardstein, et al. (1995), Arterioscler Thromb Vasc Biol 15(9): 1412-8. Abstract: HDLs encompass structurally heterogeneous particles that fulfill specific functions in reverse cholesterol transport. Two-dimensional nondenaturing polyacrylamide gradient gel electrophoresis (2D-PAGGE) of normal plasma and subsequent immunoblotting with anti-apolipoprotein (apo) A-I antibodies differentiates an abundant particle with electrophoretic alpha-mobility and less abundant particles with electrophoretic pre-beta-mobility (pre beta 1-LpA-I, pre beta 2-LpA-I, pre beta 3-LpA-I). Immunodetection with anti-apoA-II antibodies identifies a single particle with alpha-mobility. To differentiate alpha-migrating HDL without apo A-II (alpha-LpA-I) from those with apoA-II (alpha-LpA-I/A-II), we combined 2D-PAGGE with immunoadsorption of apoA-II. Incubation of plasma with 3Hcholesterol-labeled fibroblasts in combination with immunosubtracting 2D-PAGGE allowed us to analyze the role of alpha-LpA-I and alpha-LpA-I/A-II in the uptake and esterification of cell-derived cholesterol in native plasma. Depending on the duration of incubations with cells, alpha-LpA-I took up two to four times more 3Hcholesterol than alpha-LpA-I/A-II. Irrespective of the duration of incubation, two to three times more 3Hcholesteryl esters accumulated in alpha-LpA-I than in alpha-LpA-I/A-II. Subsequent incubations in the presence of an inhibitor of lecithin:cholesterol acyltransferase led to preferential accumulation of 3Hcholesteryl esters in alpha-LpA-I/A-II. In conclusion, our data indicate that alpha-LpA-I is more effective than alpha-LpA-I/A-II in both uptake and esterification of cell-derived cholesterol. Moreover, alpha-LpA-I/A-II appears to accumulate cholesteryl esters, at least partially, from alpha-LpA-I. |
| Cholesterol efflux, lecithin-cholesterol acyltransferase activity, and pre-beta particle formation by serum from human apolipoprotein A-I and apolipoprotein A-I/apolipoprotein A-II transgenic mice consistent with the latter being less effective for reverse cholesterol transport Castro, G., L. P. Nihoul, et al. (1997), Biochemistry 36(8): 2243-9. Abstract: Studies assessing fatty streak formation in mice have revealed that human apolipoprotein A-I (apoAI) transgenic mice (TgAI) have 15-fold less atherosclerosis susceptibility than combined human apolipoprotein A-I/human apolipoprotein A-II (apoAI:AII) transgenics (TgAI:AII) and 40-fold less than nontransgenic control mice. In order to examine the biochemical mechanisms underlying those in vivo observations, we have compared in vitro properties of serum from the different groups of animals for participation in cholesterol efflux, LCAT activation, and pre-beta particle formation. Analysis of cholesterol efflux from both Fu5AH hepatoma and Ob1771 adipose cells revealed serum from the TgAI to be the most efficient in promoting efflux. The two-dimensional electrophoresis of mouse serum shows that control mice have exclusively apoAI in alpha particles. TgAI and TgAI:AII mice have 30 and 38% of total apoAI in particles with pre-beta electrophoretic mobility, respectively. The distribution of cell-derived cholesterol between these apoAI-containing lipoprotein subspecies after 1 and 60 min of incubation with Fu5AH hepatoma cells was examined. This revealed after a 1 min incubation 66 +/- 8 and 83 +/- 9% of the counts in particles with pre-beta mobility for TgAI and TgAI:AII mice, respectively; while after 60 min of incubation, only 6 +/- 2% of counts remained in pre-beta particles from the TgAI and 30 +/- 3% for the TgAI:AII. This suggests faster movement of cholesterol from pre-beta to alpha particles in plasma from the TgAI. Consistent with this is the observation that LCAT activity with both exogenous and endogenous substrate increased in the TgAI versus the TgAI:AII mice. The previously observed decrease in fatty streak formation in the TgAI versus the TgAI:AII and control mice is consistent with the in vitro studies presented here and suggests that HDL containing human apoAI is a more effective participant in the postulated early steps in reverse cholesterol transport than HDL containing both human apoAI and human apoAII, and/or murine HDL. |
| Cholesterol efflux-mediated signal transduction in mammalian sperm. beta-cyclodextrins initiate transmembrane signaling leading to an increase in protein tyrosine phosphorylation and capacitation Visconti, P. E., H. Galantino-Homer, et al. (1999), J Biol Chem 274(5): 3235-42. Abstract: Sperm capacitation in vitro is highly correlated with an increase in protein tyrosine phosphorylation that is regulated by cAMP through a unique mode of signal transduction cross-talk. The activation of this signaling pathway, as well as capacitation, requires bovine serum albumin (BSA) in the incubation medium. BSA is hypothesized to modulate capacitation through its ability to remove cholesterol from the sperm plasma membrane. Here we demonstrate that the cholesterol-binding heptasaccharides, methyl-beta-cyclodextrin and OH-propyl-beta-cyclodextrin, promote the release of cholesterol from the mouse sperm plasma membrane in media devoid of BSA. Both of these beta-cyclodextrins were also demonstrated to increase protein tyrosine phosphorylation in the absence of BSA in both mouse and bull sperm, and the patterns of phosphorylation were similar to those induced by media containing BSA. The potency of the different beta-cyclodextrins to increase protein tyrosine phosphorylation in sperm was correlated with their cholesterol binding efficiencies, and preincubation of the beta-cyclodextrins with cholesterol-SO4- to saturate their cholesterol-binding sites blocked the ability of these compounds to stimulate protein tyrosine phosphorylation. The beta-cyclodextrin effect on protein tyrosine phosphorylation was both NaHCO3 and protein kinase A-dependent. The beta-cyclodextrins were also able to capacitate mouse sperm in the absence of BSA, as measured by the ability of the zona pellucida to induce the acrosome reaction and by successful fertilization in vitro. In summary, beta-cyclodextrins can completely replace BSA in media to support signal transduction leading to capacitation. These data further support the coupling of cholesterol efflux to the activation of membrane and transmembrane signaling events leading to the activation of a unique signaling pathway involving the cross-talk between cAMP and tyrosine kinase second messenger systems, thus defining a new mode of cellular signal transduction initiated by cholesterol release. |
| Cholesterol efflux-mediated signal transduction in mammalian sperm: cholesterol release signals an increase in protein tyrosine phosphorylation during mouse sperm capacitation Visconti, P. E., X. Ning, et al. (1999), Dev Biol 214(2): 429-43. Abstract: We previously demonstrated that mouse sperm capacitation is accompanied by a time-dependent increase in protein tyrosine phosphorylation that is dependent on the presence of BSA, Ca2+, and NaHCO(3), all three of which are also required for this maturational event. We also demonstrated that activation of protein kinase A (PK-A) is upstream of this capacitation-associated increase in protein tyrosine phosphorylation. BSA is hypothesized to modulate capacitation through the removal of cholesterol from the sperm plasma membrane. In this report, we demonstrate that incubation of mouse sperm medium containing BSA results in a release of cholesterol from the sperm plasma membrane to the medium; release of this sterol does not occur in medium devoid of BSA. We next determined whether cholesterol release leads to changes in protein tyrosine phosphorylation. Blocking the action of BSA by adding exogenous cholesterol-SO-(4) to the BSA-containing medium inhibits the increase in protein tyrosine phosphorylation as well as capacitation. This inhibitory effect is overcome by (1) the addition of increasing concentrations of BSA at a given concentration of cholesterol-SO-(4) and (2) the addition of dibutyryl cAMP plus IBMX. High-density lipoprotein (HDL), another cholesterol binding protein, also supports the capacitation-associated increase in protein tyrosine phosphorylation through a cAMP-dependent pathway, whereas proteins that do not interact with cholesterol have no effect. HDL also supports sperm capacitation, as assessed by fertilization in vitro. Finally, we previously demonstrated that HCO-(3) is necessary for the capacitation-associated increase in protein tyrosine phosphorylation and demonstrate here, by examining the effectiveness of HCO-(3) or BSA addition to sperm on protein tyrosine phosphorylation, that the HCO-(3) effect is downstream of the site of BSA action. Taken together, these data demonstrate that cholesterol release is associated with the activation of a transmembrane signal transduction pathway involving PK-A and protein tyrosine phosphorylation, leading to functional maturation of the sperm. |
| Cholesterol emboli neuropathy Bendixen, B. H., D. S. Younger, et al. (1992), Neurology 42(2): 428-30. Abstract: We report the clinical and pathologic features of a patient with peripheral neuropathy that was the first clinical expression of cholesterol emboli syndrome (CES). Biopsy of skeletal muscle and peripheral nerve revealed cholesterol clefts in lumens of small arteries, necrotizing arteritis, and severe degeneration of peripheral and intramuscular nerves. At autopsy, the peripheral nervous system was extensively affected by similar changes. We conclude that (1) peripheral neuropathy may be the initial manifestation of CES. Presumably, deposition of cholesterol leads to arteritis. (2) The underlying pathology of CES neuropathy is chronic axonal degeneration, possibly due to chronic ischemia of epineurial arteries. (3) Muscle biopsy is important in the antemortem diagnosis of CES. Nerve biopsy may show involvement of epineurial vessels. (4) CES may resemble polyarteritis nodosa clinically and pathologically. (5) CES may be under-recognized and should be included in the differential diagnosis of any neuropathy of uncertain cause, particularly when there is a history of vascular catheterization, or severe aortic atherosclerosis. |
| Cholesterol emboli syndrome following cardiac catheterization Freund, N. S. (1990), Postgrad Med 87(5): 55-60. Abstract: Cholesterol emboli syndrome should always be considered in an elderly patient with acute renal failure or cutaneous lesions following an invasive vascular procedure or surgery. Laboratory findings that suggest atheroemboli include eosinophilia, an elevated erythrocyte sedimentation rate, leukocytosis, and anemia. Diagnosis is made by biopsy of the affected organ, and treatment is supportive. Patients usually die of multisystem failure. |
| Cholesterol emboli with neurologic manifestation in the spinal cord Desnuelle, C., M. Lanteri-Minet, et al. (1992), Rev Neurol (Paris) 148(11): 715-8. Abstract: A 71-year old man presented with a progressive chronic paraparesis combined with inflammatory biological features including hypereosinophilia and an aneurysm of the abdominal aorta. Disseminated cholesterol embolization of arterioles was evidenced by the identification of cholesterol crystals in biopsies of the quadriceps muscle and of an iliac lymph node. Despite the lack of post mortem study of the spinal cord, the presentation was highly suggestive of cholesterol emboli in the spinal arteries. Only ten documented cases have been reported. |
| Cholesterol embolisation syndrome after thrombolytic therapy for myocardial infarction Pochmalicki, G., L. Feldman, et al. (1992), Lancet 339(8784): 58-9. |
| Cholesterol embolism after intravenous anisoylated plasminogen streptokinase activator complex (APSAC) Beutler, J. J., M. A. Sulzer, et al. (1991), Neth J Med 39(5-6): 373-4. |
| Cholesterol embolism of bone marrow clinically masquerading as systemic or metastatic tumor Muretto, P., A. Carnevali, et al. (1991), Haematologica 76(3): 248-50. Abstract: A case of cholesterol embolism of bone marrow, concerning the pelvis and lumbar region and clinically masquerading as systemic disease or metastatic tumor, is reported in an 82-year-old man hospitalized for acute onset of reddish purple nodules on the legs and toes, intense myalgia and dorsal vertebral bone pain. The clinical manifestations leading to consideration of a systemic disease or metastatic tumor were the abnormal bone scintigraphic findings of the pelvis and lumbar region, the elevation of serum alkaline and acid phosphatase and the increase of the bone isoenzyme fractions. The diagnosis of cholesterol embolism was explained by the histological findings of bone marrow biopsy which showed microinfarctions of bone marrow with an osteoproductive and reparative process, and presence of cholesterol clefts. |
| Cholesterol embolism of the kidney Meyrier, A. and P. Buchet (1990), Dtsch Med Wochenschr 115(50): 1917-20. |
| Cholesterol embolism to the skin Borrego, L., R. Gil, et al. (1992), Clin Exp Dermatol 17(6): 424-6. Abstract: The clinical features of a patient with cholesterol embolism are presented. Histopathological examination showed the typical clefts of cholesterol in the skin and renal vessels. We believe this entity is under-reported in the dermatological literature. |
| Cholesterol embolism: an infrequent cause of ischemic ulcers of the lower extremities Martinez Perez, M., J. Varela Duran, et al. (1992), Angiologia 44(2): 50-3. Abstract: A case of cholesterol embolism with digital ulcerations is reported. Pathologic anatomy, Radiologic images, symptomatology and treatment of such pathology are discussed. |
| Cholesterol embolism: an underdiagnosed clinical entity Om, A., S. Ellahham, et al. (1992), Am Heart J 124(5): 1321-6. |
| Cholesterol embolization after intravenous streptokinase therapy in acute myocardial infarction Bucher, A. and B. Roald (1993), Tidsskr Nor Laegeforen 113(15): 1844-5. Abstract: The cholesterol embolization syndrome occurs in patients with extensive atherosclerotic disease as a consequence of the showering of cholesterol-rich material from ulcerated atheromatous plaques into the arterial circulation. Cholesterol embolization has been described after angiographic procedures, vascular surgery or anticoagulation therapy and may cause manifestations from multiple organ systems. Only recently, this syndrome has been reported following intravenous thrombolytic treatment for myocardial infarction. We describe one patient who developed cholesterol embolization syndrome with extensive peripheral manifestations after intravenous streptokinase treatment for myocardial infarction. He developed livedo reticularis, with multiple symmetrical skin necrosis and ulcerations below the umbilical region. Repeated histology from ulcerations failed to demonstrate cholesterol crystals in thromboses, only revealing ischemic changes and lack of vasculitis. The patient died of a new myocardial infarction six months after the streptokinase treatment. The abdominal aorta below the renal arteries was covered by extensive atheromatous masses, with partly ulcerated intima. |
| Cholesterol embolization following angiography Henderson, M. J. and A. R. Manhire (1990), Clin Radiol 42(4): 281-2. Abstract: A case of cholesterol embolism following mesenteric angiography is reported. Although usually associated with a difficult study in atheromatous vessels this lethal complication occurred in an otherwise uncomplicated examination. This serves as a reminder of the attendant hazards of vascular studies in such patients and emphasizes the need for a careful technique to minimize any vessel wall trauma. |
| Cholesterol embolization following coronary angioplasty Fuks, D. F., R. E. Griguoli, et al. (1992), Rev Port Cardiol 11(12): 1089-91. Abstract: Cholesterol emboli syndrome is an uncommon complication seen after an invasive vascular procedure or surgery in a patient with atherosclerotic disease. The obstruction of small arteries by cholesterol crystals may be responsible for its clinical features, such as livedo reticularis, "purple toe" syndrome, renal failure, involvement of the gastrointestinal tract, coronary arteries, central nervous system or the multiple cholesterol emboli syndrome. Certain laboratory abnormalities are frequently associated: an elevated erythrocyte sedimentation rate and eosinophilia, BUN and creatinine increase in the cases with renal failure and creatine phosphokines augmentation suggesting muscle involvement. Disseminated microemboli composed mainly of cholesterol crystals are the usual pathological findings. A case of cholesterol embolism occurring after left heart catheterization and percutaneous transluminal coronary angioplasty is reported. Twenty-four hours after the procedure, the patient developed purplish discoloration of toes and soles, livedo reticularis on lumbar region, buttocks and limbs, and renal failure. Patient did well two months after anticoagulant therapy. Prognosis of these cases is related to the extent of systemic involvement and the most significant impact on this syndrome can be made by its prevention. |