Cholesterol Articles and Abstracts

For medical practitioners and the general public - Cholesterol Journal Article Catalog.

Cholesterol Journal Articles



Record 11001 to 11020
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Results of cholesterol screening in Budapest
Czeizel, E., L. Romics, et al. (1992), Orv Hetil 133(4): 254-5.

Results of new statin trials: should the low-density lipoprotein cholesterol treatment guidelines be revised?
Ross, A. M. and T. G. Ganiats (2005), Curr Atheroscler Rep 7(1): 11-6.
Abstract: In December 2002, the National Cholesterol Education Program published its third expert panel report on the detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Since then, many new studies suggest that a more aggressive approach should be taken in cholesterol therapy. Based on these new clinical trials, the National Cholesterol Education Program published recommended modifications to the Adult Treatment Panel III guidelines in July 2004. There is good evidence to support the proposed modifications to Adult Treatment Panel III, but there is still much uncertainty in many patient subsets. More evidence is necessary to clarify if current treatment guidelines and low-density lipoprotein cholesterol goals are optimal for all patients within each risk category. These guidelines, and the proposed modifications, should be used as a tool to guide therapy that should be tailored to fit the overall risk assessment and needs of the individual patient.

Results of recent large cholesterol-lowering trials and implications for clinical management
Gotto, A. M., Jr. (1997), Am J Cardiol 79(12): 1663-6.
Abstract: Three recent large clinical trials-the West of Scotland Coronary Prevention Study, the Scandinavian Simvastatin Survival Study, and the Cholesterol and Recurrent Events Trial-have all confirmed that cholesterol lowering with HMG-CoA reductase inhibitors is safe and effective therapy to prevent an initial or recurrent coronary event in patients at high risk for coronary heart disease. However, a number of questions related to the treatment of lipid disorders and risk reduction for coronary heart disease remain, including the cholesterol concentration at which treatment would best be initiated, the optimal cholesterol reduction or goal to be attained, and the mechanisms by which HMG-CoA reductase inhibitors reduce the risk for clinical events.

Results of the Massachusetts Model Systems for Blood Cholesterol Screening Project
Havas, S., L. Koumjian, et al. (1991), Jama 266(3): 375-81.
Abstract: OBJECTIVE.--To evaluate the effectiveness of a model blood cholesterol screening program. DESIGN.--Principal components included physician education, community-based screenings, and follow-up. A lay or professional educator provided counseling and referral advice. Half of the subjects with high blood cholesterol levels received a reminder to see their physician. SETTING.--135 sites in four Massachusetts communities. PARTICIPANTS.--10,428 adults. Males, the young, the poor, the less educated, and minorities were underrepresented. MAIN OUTCOME MEASURES.--Referral completion rates, blood cholesterol changes. RESULTS.--51.5% of those referred had visited their physicians within 2 to 4 months, increasing to 65.6% within 6 to 12 months. Older age (odds ratio OR, 1.17 per additional decade), more education (OR, 1.17 per additional level), higher blood cholesterol levels (OR, 1.19 per additional 0.51 mmol/L), previous knowledge of level (OR, 1.34), and receiving a reminder (OR, 1.24) were significantly associated with greater likelihood of referral completion, whereas the type of educator providing counseling was not. Physicians had remeasured the blood cholesterol level of 76% of those seen, given dietary counseling to 70%, and prescribed medication to 15%. Significant changes in dietary fat were reported by both compliers and noncompliers with advice to follow up with their physicians. Six months after screening, blood cholesterol levels were 3.6% lower in noncompliers, 4.4% lower in compliers not taking cholesterol-lowering medications, and 8.8% in compliers taking such medications. CONCLUSIONS.--An effective, community-based blood cholesterol screening program can attract diverse populations and can result in most participants with high levels following up with their physicians, making dietary changes, and lowering their cholesterol levels. Additional strategies may be needed to attract underrepresented groups and to reduce the apparent overuse of cholesterol-lowering medications.

Results of the National Cholesterol Education (NCEP) Program Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II survey and implications for treatment under the recent NCEP Writing Group recommendations
Davidson, M. H., K. C. Maki, et al. (2005), Am J Cardiol 96(4): 556-63.
Abstract: The most recent national survey of compliance with the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) guidelines was completed before ATP III and showed significant underachievement of low-density lipoprotein (LDL) cholesterol goals. The NCEP Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II was a national survey conducted in 2003. Of the 4,885 patients, 67% achieved their LDL cholesterol treatment goal, including 89%, 76%, and 57%, respectively, in the 0 or 1 risk factor, > or = 2 risk factors or coronary heart disease (CHD), and CHD risk equivalent categories. The percentage with triglyceride concentrations > or = 200 mg/dl (2.25 mmol/L) in each risk category who achieved their LDL cholesterol and non-high-density lipoprotein cholesterol goals was 64%, 52%, and 27%, respectively. Patients with diabetes (55%) and other CHD risk equivalents (40%) were less likely to have achieved their LDL cholesterol targets than those with CHD (62%). Of the 1,447 patients with cardiovascular disease, 75% could be classified as very high risk according to the new July 2004 NCEP Writing Group recommendations, and 17.8% of those at very high risk had an LDL cholesterol level of <70 mg/dl (<1.81 mmol/L). In conclusion, these results suggest improved lipid management compared with previous surveys. The largest treatment gaps were found for features new to ATP III as of July 2004, including goal achievement for patients with CHD risk equivalents and for non-high-density lipoprotein cholesterol targets. Most of those (75%) with cardiovascular disease in NEPTUNE II would be considered very high risk and candidates for aggressive therapy to reach the new optional treatment goals.

Retention and separation studies of cholesterol and bile acids using thermostated thin-layer chromatography
Zarzycki, P. K., M. Wierzbowska, et al. (1999), J Chromatogr A 857(1-2): 255-62.
Abstract: The influence of temperature on retention and separation of cholesterol and bile acids, using reversed-phase thin-layer chromatography, was studied. As mobile phases methanol-water mixtures of various compositions were used. Chromatographic experiments were performed using vapor-saturated chambers at temperatures ranging from 5 to 60 degrees C. A linear relationship between R(M) values and temperature (1/T) as well as mobile phase composition was observed. The elution order of steroids under the conditions investigated was discussed. Each chromatogram was evaluated using simple optimization parameters and the best chromatographic conditions for the separation of multicomponent samples were chosen.

Retention of fluorescent-labelled chylomicron remnants within the intima of the arterial wall--evidence that plaque cholesterol may be derived from post-prandial lipoproteins
Proctor, S. D. and J. C. Mamo (1998), Eur J Clin Invest 28(6): 497-503.
Abstract: Plaque cholesterol is thought to be derived exclusively from low-density lipoproteins that have become trapped and modified in the subendothelial space of arterial vessels. However, in this study we provide the first visual evidence that demonstrates that (a) remnants of post-prandial lipoproteins rapidly penetrate arterial tissue; (b) efflux is not complete; and (c) focal accumulation of chylomicron remnants occurs within the subendothelial space. The arterial retention of chylomicron remnants is consistent with atherogenesis being in part a post-prandial phenomenon.

Retention of prominin in microvilli reveals distinct cholesterol-based lipid micro-domains in the apical plasma membrane
Roper, K., D. Corbeil, et al. (2000), Nat Cell Biol 2(9): 582-92.
Abstract: Membrane cholesterol-sphingolipid 'rafts', which are characterized by their insolubility in the non-ionic detergent Triton X-100 in the cold, have been implicated in the sorting of certain membrane proteins, such as placental alkaline phosphatase (PLAP), to the apical plasma membrane domain of epithelial cells. Here we show that prominin, an apically sorted pentaspan membrane protein, becomes associated in the trans-Golgi network with a lipid raft that is soluble in Triton X-100 but insoluble in another non-ionic detergent, Lubrol WX. At the cell surface, prominin remains insoluble in Lubrol WX and is selectively associated with microvilli, being largely segregated from the membrane subdomains containing PLAP. Cholesterol depletion results in the loss of prominin's microvillus-specific localization but does not lead to its complete intermixing with PLAP. We propose the coexistence within a membrane domain, such as the apical plasma membrane, of different cholesterol-based lipid rafts, which underlie the generation and maintenance of membrane subdomains.

Retiree awareness of levels of blood pressure and cholesterol
Blount, B. W. and J. B. Brown (1996), Mil Med 161(11): 683-6.
Abstract: PURPOSE: Determine the level of awareness of cholesterol and blood pressure in a retiree population; assess factors indicating a higher risk for lack of awareness. METHODS: A cross-sectional survey was mailed to a random sample of 9.5% of the 7,400 retiree households served by an Army community hospital. Data analysis used descriptive statistics and t test for continuous data and chi-square for categorical data. RESULTS: Response rate was 71.4%. Overall, 45.8 and 37.9% of the respondents have accurate knowledge of the levels of their blood pressure and cholesterol, respectively. For those with documented hypertension and hyperlipidemia, the correct awareness levels are 78.5 and 63.4%, respectively. The only sociodemographic factor associated with correct awareness is age with cholesterol knowledge. CONCLUSIONS: This population meets the objectives set by Healthy People 2000 for cholesterol awareness, but not for blood pressure. The overall levels of awareness compare favorably to results from other studied populations. Physicians are not using all opportunities to educate patients about modifiable risk factors.

Reversal of atherosclerotic obstructions by percutaneous transluminal angioplasty raises high-density lipoprotein cholesterol
Steurer, J., H. Drexel, et al. (1995), Vasa 24(1): 15-8.
Abstract: Variation of high-density lipoprotein cholesterol (HDL) levels in man show a strong inverse relationship to the incidence of atherosclerotic vascular disease. Conversely, effects of atherosclerosis and ischemia on lipoprotein metabolism are unclear. We investigated 41 patients, 10 women and 31 men, undergoing percutaneous transluminal angioplasty by measuring fasting lipoprotein cholesterol including high-density lipoprotein subfraction analysis before and one as well as 12 weeks after the procedure. Successful reopening of a haemodynamically significant iliac, femoral or popliteal obstruction was achieved in all patients. A highly significant (p < 0.001) increase of HDL cholesterol from 1.10 +/- 0.05 to 1.31 +/- 0.06 mmol/l was revealed 12 weeks later. This was due to a significant (p < 0.001) increase in HDL3 cholesterol by 26%, whereas HDL2 cholesterol did not change significantly. We conclude that HDL cholesterol levels increase after recanalization of a significant atherosclerotic obstruction which may be a direct effect of reperfusion or an indirect effect due to an increase in exercise tolerance.

Reversal of extrahepatic membrane cholesterol deposition in patients with chronic liver diseases by S-adenosyl-L-methionine
Rafique, S., M. Guardascione, et al. (1992), Clin Sci (Lond) 83(3): 353-6.
Abstract: 1. S-Adenosyl-L-methionine is reported to improve serum liver function tests in chronic liver disease. Because liver disease is complicated by cholesterol deposition in hepatic and extrahepatic membranes, we have assessed whether oral administration of S-adenosyl-L-methionine to patients with hepatic disease can reverse the cholesterol enrichment of their erythrocytes. 2. The mean erythrocyte cholesterol-to-phospholipid molar ratio in 13 jaundiced patients was reduced 2 weeks after oral administration of S-adenosyl-L-methionine (from 0.874 +/- 0.112 to 0.844 +/- 0.102, P < 0.05) with 10 of the patients (77%) showing a decrease. By contrast, only four of 11 untreated patients (36%) had a reduced erythrocyte cholesterol-to-phospholipid molar ratio after 2 weeks and the mean values did not differ. 3. The plasma and erythrocyte cholesterol-to-phospholipid molar ratios remained closely correlated (r = 0.77, P < 0.01) before and after treatment, suggesting that S-adenosyl-L-methionine had not acted directly on the cells but rather had improved their lipoprotein milieu. Further support for this concept was provided by following one patient, who initially failed to respond, during an additional 3 weeks of S-adenosyl-L-methionine administration. The plasma cholesterol-to-phospholipid molar ratio fell steadily from week 1 to week 5 and was accompanied by a progressive decrease in the erythrocyte cholesterol-to-phospholipid molar ratio. Moreover, the initially suppressed acetylcholinesterase activity of the erythrocyte membranes returned towards normal during this period. 4. This preliminary study is the first evidence in jaundiced patients that a drug can help to reverse the deposition of cholesterol in an extrahepatic membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Reverse cholesterol transport
Schmidt, H. H. and M. P. Manns (1996), Z Gastroenterol 34(6): 386-91.

Reverse cholesterol transport and atherosclerosis regression
Spady, D. K. (1999), Circulation 100(6): 576-8.

Reverse cholesterol transport and future pharmacological approaches to the treatment of atherosclerosis
Krause, B. R. and B. J. Auerbach (2001), Curr Opin Investig Drugs 2(3): 375-81.
Abstract: The apparent protective effect of high density lipoprotein cholesterol (HDL) with respect to coronary heart disease (CHD) is generally thought to reside in its ability to transport cholesterol from peripheral cells to the liver for excretion from the body. Knozon as reverse cholesterol transport (RCT), this process involves many key steps and lipoprotein interconversions, and there is no consensus as to which step is most suitable for possible drug intervention. The membrane proteins, scavenger receptor class B, type 1 (SR-B1) and the ATP-binding cassette 1 (ABC1), have been strongly implicated as being important in cholesterol efflux; the former as a bona fide receptor for HDL and the latter as a lipid transporter. Lecithin:cholesterol acyltransferase (LCAT) then esterifies the effluxed cholesterol to form cholesteryl esters (Step 2), which are then transferred to apoB-containing lipoproteins by cholesteryl ester transfer protein (CETP, Step 3). Despite the complexities and uncertainties, drugs should be developed which impact all of the above steps, and short-term endpoints need to be defined for a cautious, systematic approach to clinical evaluation.

Reverse cholesterol transport and use of transgenic mice and rabbits to reveal candidate genes for protection against atherosclerosis
Fruchart, J. C. and P. Duriez (1998), Bull Acad Natl Med 182(2): 233-47; discussion 247-9.
Abstract: Atherosclerosis is the leading cause of death in industrial societies. In France, 215 men out of 100,000 aged from 25 to 64 years old suffered of a myocardial infarction in 1992 and due to this disease 67 men out of 100,000 died. Hypercholesterolemia corresponding to a high LDL cholesterol level is an important risk factor of myocardial infarction. Nevertheless a low cholesterol level in the HDL fraction (frequently associated with an increase in triglycerides concentrations) is a common abnormality found in patients with confirmed coronary artery disease. Therefore, besides tentatives to reduce triglycerides and LDL cholesterol levels, a therapeutical strategy consists in increasing the serum HDL cholesterol concentration in order to improve the "reverse cholesterol transport". Apo A-I is the major protein of HDL. Studies in mice and rabbits transgenic for human apo A-I showed that overexpression of this protein in these animals resulted in an increase in the HDL cholesterol level. The serum of these animals contents a high concentration of particles containing human apo A-I but not mouse apo A-II (LpA-I) and presents a higher ability to induce cellular cholesterol efflux than the serum of the control mice. These alterations result in a reduction of atherosclerosis development when these animals are submitted to a cholesterol rich diet. Lecithin cholesterol acyl-transferase (LCAT) is a major enzyme in the metabolic cascade leading to the return of cholesterol to the liver. The metabolic role of LCAT is to esterify the free cholesterol of native HDL. Native HDL acquire free cholesterol during the transfer of cholesterol from the cell membrane to the particle during the cellular cholesterol efflux, which is the first step of the "reverse cholesterol transport". Mice and rabbits transgenic for human LCAT have higher HDL-cholesterol levels. Transgenic rabbits but not transgenic mice are protected against diet induced atherosclerosis development. Nevertheless, cholesterol fed mice which are transgenic for both human LCAT and simian cholesteryl ester transfer (CETP) protein do not develop atherosclerosis. This data indicates that over production of LCAT reduces atherosclerosis when CETP is naturally (rabbit) or artificially (CETP transgenic mice) expressed in the animals. Tentatives of gene therapy in mice induced by adenovirus-mediated transfer of human apo A-I and LCAT genes also increased circulating apo A-I and LCAT. Therefore apo A-I and LCAT are two potential targets for gene therapy in patients with atherosclerosis associated with a low HDL cholesterol level.

Reverse cholesterol transport from the perfused spleen in the presence or absence of a perfused liver
Mindham, M. A. and P. A. Mayes (1993), Biochem Soc Trans 21(2): 146S.

Reverse cholesterol transport in cultured gallbladder epithelial cells
Lee, J. and H. S. Choi (2004), Korean J Gastroenterol 43(3): 145-52.
Abstract: Bile is the major route of cholesterol excretion from the body. It is concentrated in the gallbladder, and often results in supersaturation of cholesterol. The high levels of cholesterol in gallbladder bile has clinical implications with respect to cholesterol gallstone formation and cholesterolosis of the gallbladder wall. Gallbladder epithelial cells (GBEC) are exposed to high cholesterol concentrations on their apical surfaces. Therefore, GBEC are uniquely positioned to play an important role in modulating biliary cholesterol concentrations. Recently, it has been documented that the key-transporter for polarized cholesterol and phospholipid efflux in GBEC is ATP-binding cassette transporter A1 (ABCA1) and Liver X receptor (LXR) and retinoid X receptor (RXR) in the nucleus of GBEC have a role that regulates ABCA1 expression. In addition, GBEC synthesize apolipoprotein A-I and E as cholesterol acceptors. These results indicate that GBEC has a perfect system for reverse cholesterol transport. We introduce the roles and mechanisms of ABCA1, scavenger receptor class B-I, LXR and RXR related to reverse cholesterol transport in GBEC with a review of our study experience and related literature.

Reverse cholesterol transport in diabetes mellitus
Quintao, E. C., W. L. Medina, et al. (2000), Diabetes Metab Res Rev 16(4): 237-50.
Abstract: There are epidemiological data and experimental animal models relating the development of premature atherosclerosis with defects of the reverse cholesterol transport (RCT) system. In this regard, the plasma concentrations of the high density lipoprotein (HDL) subfractions, of cholesteryl ester transfer protein (CETP), as well as the activity of the enzyme lecithin-cholesterol acyl transferase (LCAT) play critical roles. However, there has been plenty of evidence that atherosclerosis in diabetes mellitus (DM) is ascribed to a greater arterial wall cell uptake of modified apoB-containing lipoproteins whereas a primary or predominant defect of the RCT system is still a subject of debate. In other words, in spite of the fact that in DM the composition and rates of metabolism of the HDL particles are greatly altered and display a diminished in vitro efficiency to remove cell cholesterol, definitive in vivo demonstration of the importance of this fact in atherogenesis is lacking. Furthermore, the roles played by LCAT and CETP in RCT in DM are difficult to interpret because the in vitro procedures of measurement utilized have either been inadequate, or inappropriately interpreted. Knock-out or transgenic mice are much needed models to investigate the roles of LCAT, CETP, phospholipid transfer protein (PLTP), and of a CETP inhibitor in the development of atherosclerosis of experimental DM.

Reverse cholesterol transport in man: promotion of fecal steroid excretion by infusion of reconstituted HDL
Angelin, B., P. Parini, et al. (2002), Atheroscler Suppl 3(4): 23-30.
Abstract: Reverse cholesterol transport is a complex process, which transfers cholesterol from peripheral cells to the liver for subsequent elimination as bile acids and neutral steroids. Although apo A-I in high density lipoproteins (HDL) is believed to have a crucial role in this process, clinical conditions with very low HDL cholesterol levels appear to maintain normal cholesterol excretion. On the other hand, infusion of 'artificial HDL' in the form of recombinant proapo A-I (4 g) liposome complexes results in increased fecal steroid excretion, corresponding to a removal of approximately 0.5 g cholesterol daily for up to 9 days. This occurs without evidence of increased cholesterol synthesis, and could not be reproduced by infusion of liposomes only. These data indicate that stimulation of reverse cholesterol transport may be induced by infusion of 'artificial HDL' in humans, and that a more detailed knowledge of this process may be useful in the treatment of atherosclerosis.

Reverse cholesterol transport in mice expressing simian cholesteryl ester transfer protein
Stein, O., Y. Dabach, et al. (2002), Atherosclerosis 164(1): 73-8.
Abstract: The role of cholesteryl ester transfer protein (CETP) in atherogenesis remains ambiguous, as both pro and antiatherogenic effects have been described. Expression of CETP increases HDL-cholesteryl ester turnover, but there is no direct evidence whether CETP mobilizes cholesterol in vivo. The rate of cholesterol removal injected into a leg muscle as cationized low density lipoprotein (cat-LDL) was compared in CETP transgenic and control mice. Four days after injection the exogenous cholesterol mass retained in muscle was 65% in CETP transgenic and 70% of injected dose in controls; it decreased to 52-54% by day 8 and negligible amounts remained on day 28. The cat-LDL was labeled with either 3H-cholesterol oleate (3H-CE) or 3H-cholesteryl oleoyl ether (3H-COE), a nonhydrolyzable analog of 3H-CE. After injection of 3H-CE cat-LDL, clearance of 3H-cholesterol had a t(1/2) of 4 days between day 4 and 8 but there was little loss of 3H-COE between day 4 and 51. Liver radioactivity on day 4 was 1.7% in controls and 3.4% in CETP transgenics; it was 2.8 and 4.6%, respectively, on day 8. 3H-COE in liver accounted for 60% of label in CETP transgenics. In conclusion, high levels of plasma CETP in mice do not enhance reverse cholesterol transport in vivo but may act on extracellularly located cholesteryl ester.


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