| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Remnant lipoprotein cholesterol and triglyceride reference ranges from the Framingham Heart Study McNamara, J. R., P. K. Shah, et al. (1998), Clin Chem 44(6 Pt 1): 1224-32. Abstract: Remnants of triglyceride-rich lipoproteins of both intestinal and liver origin are considered atherogenic, but they have been difficult to isolate and measure. An assay has been developed that allows the measurement of remnant-like particle cholesterol (RLP-C) and triglyceride (RLP-TG). RLP-C and RLP-TG concentrations were measured in >3000 fasting plasma samples obtained from participants in exam cycle 4 of the Framingham Offspring Study and stored at -80 degrees C. After exclusions, comparisons were made for 2821 samples (1385 women, 1436 men; mean age, 52 years). For women, the mean RLP-C and RLP-TG values were 0.176 +/- 0.058 mmol/L (6.8 +/- 2.3 mg/dL) and 0.204 +/- 0.159 mmol/L (18.1 +/- 14.1 mg/dL), respectively; for men, the mean values were 0.208 +/- 0.096 mmol/L (8.0 +/- 3.7 mg/dL) and 0.301 +/- 0.261 mmol/L (26.7 +/- 23.1 mg/dL), respectively. Women had significantly lower RLP-C and RLP-TG values (P <0.0001) than men; premenopausal women had significantly lower values than postmenopausal women (P <0.0001); and younger subjects (<50 years) had significantly lower values than older individuals (P <0.0001). The 75th percentile values for RLP-C and RLP-TG were 0.186 mmol/L (7.2 mg/dL) and 0.225 mmol/L (19.9 mg/dL), respectively, for women, and 0.225 mmol/L (8.7 mg/dL) and 0.346 mmol/L (30.6 mg/dL) for men. These data provide reference ranges for use in the evaluation of RLP-C and RLP-TG as potential indicators of risk for coronary heart disease. |
| Remnant lipoproteins are related to intima-media thickness of the carotid artery independently of LDL cholesterol and plasma triglycerides Karpe, F., S. Boquist, et al. (2001), J Lipid Res 42(1): 17-21. Abstract: Remnants of triglyceride-rich lipoproteins (TRL) have been implicated in the early development of atherosclerosis. We tested this hypothesis by quantifying the plasma concentration of remnant-like particle cholesterol (RLP-C) in a cohort of healthy 50-year-old men in whom the common carotid artery intima-media thickness (CCA-IMT) was assessed by B-mode ultrasound as a surrogate marker for atherosclerosis. The subjects were given a fat-rich meal to study the generation of RLP-C during postprandial lipemia. Fasting plasma RLP-C and other major fasting plasma lipids and lipoproteins were determined twice, and the mean RLP-C concentration was strongly correlated with CCA-IMT (r = 0.32, P = 0.002). In addition, low density lipoprotein (LDL) cholesterol (r = 0.25, P = 0.01) and plasma triglycerides (r = 0.20, P = 0.05) were significantly related to CCA-IMT. Multivariate analyses showed a triglyceride-independent contribution of RLP-C to CCA-IMT. After fat intake, the median plasma RLP-C concentration was doubled after 3 h. The increase was strongly related to the postprandial generation of TRL apolipoprotein (apo)B-48, and large (S(f) 60;-400) TRL apoB-100. The association with CCA-IMT was somewhat stronger for the 3-h RLP-C level than for the fasting RLP-C concentration r = 0.27, P < 0.01 (3 h) compared with r = 0.22, P < 0.05 (0 h).We conclude that the plasma concentration of RLP-C is related to CCA-IMT, independent of plasma triglycerides and LDL cholesterol, in a healthy middle-aged male population. - Karpe, F., S. Boquist, R. Tang, G. M. Bond, U. de Faire, and A. Hamsten. Remnant lipoproteins are related to intima-media thickness of the carotid artery independently of LDL cholesterol and plasma triglycerides. J. Lipid Res. 2001. 42: 17;-21. |
| Remnant-like lipoprotein particle cholesterol concentration and progression of coronary and vein-graft atherosclerosis in response to gemfibrozil treatment Karpe, F., M. R. Taskinen, et al. (2001), Atherosclerosis 157(1): 181-7. Abstract: Remnant lipoproteins such as chylomicron and very low density lipoprotein (VLDL) remnants have been implicated in the progression of coronary atherosclerosis. Recently, a novel method for the determination of the remnant-like lipoprotein particle cholesterol (RLP-C) concentration was developed based on immunoaffinity-separation of plasma. The compositional characteristics of RLP are strikingly similar to those of postprandially modified VLDL. In addition, the method also detects chylomicron remnants. We investigated the relationship between the plasma RLP-C concentration and the angiographic outcome of the 2-year, randomised, placebo-controlled Lipid Coronary Angiography Trial (LOCAT), which used gemfibrozil as lipid lowering agent. The RLP-C response to gemfibrozil treatment has not been described before. Gemfibrozil reduced the median RLP-C concentration by 34%. The on-treatment RLP-C concentration was significantly associated with the progression of the minimum lumen diameter (MLD) (P<0.004). The plasma levels of RLP-C as well as the change in response to treatment was closely associated with plasma triglycerides and the association between on-treatment RLP-C concentration and progression of MLD was not independent of plasma triglycerides. A significant relation was seen between RLP-C and the occurrence of new lesions in vein grafts. Subjects with one new lesion had an approximately 25% higher on-treatment RLP-C concentration and the four patients showing two new lesions had a 100% higher RLP-C concentration than patients without vein graft stenosis. A total of 19 out of 23 subjects having one new lesion, and all four patients showing two new lesions, were assigned to the placebo group. We conclude that the RLP-C concentration, which is likely to reflect the plasma cholesterol contained in postprandially modified VLDL and chylomicron remnants, is strongly associated with angiographically verified progression of focal coronary atherosclerosis, and that lowering of RLPs prevents vein graft stenosis. |
| Remnant-like particle (RLP) cholesterol is an independent cardiovascular disease risk factor in women: results from the Framingham Heart Study McNamara, J. R., P. K. Shah, et al. (2001), Atherosclerosis 154(1): 229-36. Abstract: Remnants of triglyceride-rich lipoproteins (TRL) of both intestinal and liver origin are considered to be atherogenic, but separation of remnant lipoproteins from other TRL is difficult. An assay has been developed that allows immunoseparation of remnant-like particles (RLP) and measurement of cholesterol (RLP-C) and triglyceride (RLP-TG). We measured RLP-C and RLP-TG in fast plasma samples obtained from 1567 women participating in cycle 4 of the Framingham heart study (FHS). When values from 83 women with cardiovascular disease (CVD) were compared with the values from 1484 women without disease, concentrations in women with CVD were found to be significantly higher for both RLP-C (0.215+/-0.102 vs. 0.186+/-0.162 mmol/l; +15.6%; P<0.0001) and RLP-TG (0.319+/-0.352 vs. 0.251+/-0. 716 mmol/l; +27.0%; P<0.0002). Logistic regression analysis revealed that RLP-C was significantly associated with prevalent CVD in women (P<0.002) after adjustment with other major risk factors. In conclusion, we have documented that RLP-C is an independent risk factor for CVD in women, and provides significantly more information than do triglycerides. |
| Remnant-like particle cholesterol and insulin resistance in nonobese nonhypertensive Japanese glucose-tolerant relatives of type 2 diabetic patients Fukushima, M., A. Taniguchi, et al. (2001), Diabetes Care 24(9): 1691-4. |
| Remnant-like particle cholesterol and triglyceride levels of hypertriglyceridemic patients in the fed and fasted state Marcoux, C., P. N. Hopkins, et al. (2000), J Lipid Res 41(9): 1428-36. Abstract: Potentially atherogenic triglyceride-rich lipoprotein (TRL) remnants can be isolated and quantitated as remnant-like particles (RLP), using an immunoaffinity gel containing specific anti-human apolipoprotein A-I (apoA-I) and apoB-100 monoclonal antibodies. The aim of the present study was to determine the relationship between postprandial changes in RLP levels and changes in total serum triglyceride (TG) in patients with different forms of hypertriglyceridemia (HTG). Three groups of patients were selected, having similarly elevated serum TG levels: a) HTG with TRL remnant accumulation (i.e., type III patients, n = 15, TG: 3.8 +/- 0.2 mm), b) HTG with increased LDL (i.e., type IIb patients, n = 15, TG: 3.7 +/- 0.2 mm), and c) HTG without evidence of remnant or LDL accumulation (i.e., type IV patients, n = 15, TG: 3.9 +/- 0.3 mm). Ingestion of a 45-g fat meal caused a significant increase in serum TG (30;-50%) in all patients. Mean serum TG levels of the three groups were not significantly different at 4 or 6 h after the meal. RLP cholesterol (C) and TG levels increased after the meal in all patients, but these postprandial increases were also not significantly different among groups. Type III patients had significantly higher (P < 0.01) levels of RLP-C and RLP-apoE in the fasted and fed state, and also had significantly higher RLP-C-to-serum TG ratios (P < 0.001) compared with the other groups. These results indicate that 1) RLP-C and RLP-TG levels are significantly increased in the fed versus fasted state in patients with elevated fasting TG levels; 2) patients with different forms of HTG, but similar TG levels, have similar postprandial increases in RLP-C and RLP-TG; and 3) type III patients have significantly elevated levels of RLP-C and RLP-apoE in both the fed and fasted state. |
| Remnant-like particle cholesterol is a major risk factor for myocardial infarction in vasospastic angina with nearly normal coronary artery Sakata, K., N. Miho, et al. (1998), Atherosclerosis 136(2): 225-31. Abstract: We investigated the association of remnant-like particle cholesterol (RLP-C), with vasospastic angina (VSA). We selected 66 subjects with nearly normal coronary artery as a control group, and 74 VSA with nearly normal coronary artery, of whom 19 had prior myocardial infarction (MI). Coronary risk factors, triglyceride, lipoproteins and apolipoproteins were evaluated using stepwise discriminant analysis, smoking was the only discriminator of the control group from VSA and RLP-C was the only discriminator of VSA with MI from VSA without MI. In comparison between VSA with and without MI, using stepwise logistic regression analysis, the only significant variable was RLP-C, and odds ratio of RLP-C for MI was 1.59. Thus, RLP-C is a major discriminator of VSA with MI and appears to be a major risk factor for MI in VSA. |
| Remnant-like particle cholesterol levels in Korean patients with coronary artery disease and non-insulin dependent diabetes mellitus Song, J., H. Park, et al. (2000), Clin Chem Lab Med 38(5): 427-32. Abstract: Several studies have provided evidence that the remnants of lipoproteins may be the atherogenic components of triglyceride-rich lipoproteins. The purpose of this study was to investigate whether the remnant-like particle cholesterol (RLP-C) is an independent risk factor for coronary artery disease (CAD) and non-insulin dependent diabetes mellitus (NIDDM) in the Korean population and to explore the relationship between RLP-C and other biochemical markers as well as the apolipoprotein (apo) E genotypes. Lipid and lipoproteins including RLP-C and apo E genotypes were analyzed in 98 normal adults (control group), 68 patients with CAD (CAD group), 88 patients with NIDDM (DM group), and 19 patients with both CAD and NDDM (CAD + DM group). RLP-C levels were significantly higher in the DM (p < 0.0001), CAD (p = 0.0012) and the CAD + DM groups (p = 0.0184) than in the controls. To determine which variable could discriminate most effectively and independently among the different groups, stepwise linear discriminant analysis was performed for all the variables that showed p < 0.15 by univariate analysis. RLP-C was selected as an independent discriminator between the control and patient groups. RLP-C levels showed a strong positive correlation with trigylceride levels in the control, CAD and DM groups (r = 0.783, r = 0.610 and r = 0.746, respectively). In overall groups, apo epsilon4 and epsilon2 carrier genotypes showed a significant increase in RLP-C levels compared with epsilon3/3 wild-type (p = 0.0085). After adjusting for the effect of apo E genotypes, a significant increase of the RLP-C levels in the disease groups remained. In conclusion, RLP-C was determined to be an independent risk factor in Korean patients with CAD and NIDDM and showed a strong correlation with triglyceride levels. We suggest that the increased cardiovascular risk associated with the epsilon4 and epsilon2 allele may be mediated by more atherogenic RLP-C. |
| Remnant-like particle cholesterol levels in patients with dysbetalipoproteinemia or coronary artery disease Devaraj, S., G. Vega, et al. (1998), Am J Med 104(5): 445-50. Abstract: PURPOSE: Several studies have provided support for a proatherogenic role for remnant lipoproteins. Thus, the aim of this study was to compare remnant-like particle (RLP) cholesterol levels in patients with coronary artery disease who were normolipidemic with those in controls of similar age and gender. We also assessed the usefulness of measuring RLP-cholesterol levels in patients with type III dyslipidemia. SUBJECTS AND METHODS: Remnant-like particle cholesterol levels were measured in 63 normolipidemic men with coronary artery disease and 23 male controls of similar age as well as in 15 patients with type III dyslipidemia and 103 controls, using an immunoaffinity method. RESULTS: Remnant-like particle cholesterol levels were significantly increased in men with coronary artery disease compared with controls (7.6 +/- 3.8 mg/dL versus 5.7 +/- 1.9 mg/dL, P < 0.01). In patients with coronary artery disease, RLP-cholesterol levels were correlated with total triglyceride and nonhigh-density-lipoprotein (HDL) cholesterol levels, but not with HDL-cholesterol levels. RLP-cholesterol levels were significantly elevated in patients with type III dyslipidemia (median 119, range 31 to 240 mg/dL) compared with controls (median 5.6, range 2.2 to 10.5 mg/dL, P < 0.001). CONCLUSION: Normolipidemic men with coronary artery disease have increased levels of RLP-cholesterol that is not detected with conventional lipid screening. The RLP-cholesterol assay is a simple method for detecting high concentrations of remnant lipoproteins in patients with type III dyslipidemia. |
| Remnant-like particle cholesterol may indicate atherogenic risk in patients on chronic hemodialysis Oda, H., N. Yorioka, et al. (1997), Nephron 76(1): 7-14. Abstract: Recently, involvement of remnant-like particle cholesterol (RLP-C) in atherosclerosis was reported, but this parameter has not been adequately investigated in hemodialysis (HD) patients. The present study investigated the relationship between the RLP-C level and total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), lipid peroxides (malone dialdehyde, MDA), apolipoprotein (Apo) A-I, and ApoB. In addition, the fractions of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), LDL, and HDL in serum lipoproteins were determined by disk polyacrylamide gel electrophoresis. The relationship between the RLP-C level and three atherogenic indices was also studied. The RLP-C level in HD patients (8.2 +/- 6.7 mg/dl) was significantly higher than that in normal controls (2.7 +/- 1.3 mg/dl). The RLP-C level showed a significant positive correlation with the levels of TC, TG, LDL-C, MDA, ApoB, VLDL(%), and IDL(%), as well as a negative correlation with HDL(%). However, there was no correlation with age or the duration of HD. RLP-C also showed significant positive correlations with the (TC -HDL-C)/HDL-C ratio and the (VLDL + LDL)/HDL ratio, as well as a negative correlation with the ApoA-I/ApoB ratio. These results suggest that RLP-C may be a potential indicator of atherogenic risk in HD patients. |
| Remnant-like particle cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients Taniguchi, A., M. Fukushima, et al. (2000), Diabetes Care 23(12): 1766-9. Abstract: OBJECTIVE: The aim of the study was to investigate the relationships between remnant-like particle (RLP) cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 86 nonobese Japanese type 2 diabetic patients (72 men and 14 women, aged 40-83 years, BMI 20.1-26.6 kg/m2) were studied. BMI, HbA1c levels, and fasting concentrations of plasma glucose, serum lipids (RLP cholesterol, total cholesterol, HDL cholesterol, and triglycerides), and serum insulin were measured. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). The subjects were divided into two groups according to the value of HOMA-IR. Values >2.5 were indicative of the insulin-resistant state, and values <2.5 were indicative of the insulin-sensitive state. RESULTS: The insulin-resistant group had significantly higher RLP cholesterol and triglyceride levels and lower HDL cholesterol levels compared with the insulin-sensitive group. Univariate regression analysis showed that insulin resistance was positively correlated with BMI (r = 0.254, P = 0.019), HbA1c levels (r = 0.278, P = 0.011), RLP cholesterol levels (r = 0.315, P = 0.004), and triglyceride levels (r = 0.332, P = 0.002) and was negatively correlated with HDL cholesterol levels (r = -0.301, P = 0.006) in our diabetic patients. Multiple regression analysis showed that insulin resistance was independently associated with serum triglyceride levels, which explained 13.5% of the variability of insulin resistance in our nonobese Japanese type 2 diabetic patients. CONCLUSIONS: These results indicate that 1) nonobese Japanese type 2 diabetic patients with insulin resistance are characterized by high RLP cholesterol and triglyceride levels, and low HDL cholesterol levels; and 2) the level of serum triglycerides is an independent predictor of insulin resistance in these patients. |
| Remnant-like particle-cholesterol (RLP-C) Yamada, N. and K. Nakajima (2004), Nippon Rinsho 62 Suppl 12: 26-9. |
| Remnant-like particle-cholesterol concentrations in patients with type 2 diabetes mellitus and end-stage renal disease Hirany, S., D. O'Byrne, et al. (2000), Clin Chem 46(5): 667-72. Abstract: BACKGROUND: Lipid abnormalities contribute significantly to the increased risk of cardiovascular disease in diabetic and end-stage renal disease (ESRD) patients. Accumulating evidence supports a proatherogenic role for remnant lipoproteins. Thus, the aim of the present study was to compare remnant-like particle-cholesterol (RLP-C) in type 2 diabetic and ESRD patients with age- and gender-matched controls. METHODS: Using an immunoaffinity assay, we measured RLP-C concentrations in 48 type 2 diabetic patients with (n = 24) and without (n = 24) macrovascular complications, and 24 age- and gender-matched controls, as well as in 38 ESRD patients on hemodialysis (n = 19) and peritoneal dialysis (n = 19), and 19 age- and gender-matched controls. RESULTS: RLP-C correlated significantly with plasma triglycerides (TGs; r = 0.8). When compared with controls, RLP-C concentrations were significantly higher in type 2 diabetic patients with and without macrovascular complications (median, 0.22 and 0.17 mmol/L vs 0.14 mmol/L; P <0.0002 and <0.01, respectively); diabetic patients with macrovascular complications also had significantly higher RLP-C than diabetic patients without macrovascular complications (P <0.05). However, when RLP-C/TG ratios were computed, only diabetic patients with macrovascular complications showed significantly higher RLP-C/TG ratios compared with controls (P <0.05). Regarding ESRD, RLP-C concentrations were significantly increased in patients on both hemodialysis and peritoneal dialysis compared with controls (median, 0.23 and 0.21 mmol/L vs 0.13 mmol/L; P <0.0001). Whereas RLP-C was increased in ESRD patients on hemodialysis with TGs <2.26 mmol/L compared with controls, RLP-C/TG ratios were not significantly increased in these patients. CONCLUSIONS: Type 2 diabetic patients with macrovascular disease demonstrated increased RLP-C and RLP-C/TG ratios, whereas ESRD patients showed only increased RLP-C concentrations. |
| Remnant-like particles cholesterol is higher in diabetic patients with coronary artery disease Higashi, K., T. Ito, et al. (2001), Metabolism 50(12): 1462-5. Abstract: Diabetes mellitus (DM) has been well known to be one of the risk factors of coronary artery disease (CAD). Recently, remnant-like particles cholesterol (RLP-C) has been reported to be associated with CAD. However, few studies reported the association of RLP-C level with CAD in subjects with DM. To investigate the effects of presence or absence of DM on the association between RLP-C and CAD, we compared the RLP-C level in 142 male patients with CAD and 123 male subjects without CAD (non-CAD), including 44 and 38 DM patients, respectively. RLP-C was significantly higher in CAD than non-CAD (P <.05). RLP-C and RLP-C/plasma-triglyceride (TG) ratio in CAD with DM were higher than CAD without DM (P <.01, P <.05), and non-CAD with DM (P <.001, P <.05). There was positive correlation between RLP-C and plasma-TG in non-CAD without DM (r =.44, P <.01), non-CAD with DM (r =.56, P <.001), CAD without DM (r =.81, P <.0001), and CAD with DM (r =.75, P <.001). After excluding the hypertriglyceridemic patients (>200mg/dL), RLP-C/plasma-TG ratio was significantly higher in CAD with DM than CAD without DM (P <.001) and non-CAD with DM (P <.05). These results suggest that increased RLP-C to plasma-TG may be associated with CAD in middle-aged diabetic male subjects. |
| Remodeling and shuttling. Mechanisms for the synergistic effects between different acceptor particles in the mobilization of cellular cholesterol Rodrigueza, W. V., K. J. Williams, et al. (1997), Arterioscler Thromb Vasc Biol 17(2): 383-93. Abstract: In normal physiology, cells are exposed to cholesterol acceptors of different sizes simultaneously. The current study examined the possible interactions between two different classes of acceptors, one large (large unilamellar phospholipid vesicles, LUVs) and one small (HDL or other small acceptors), added separately or in combination to Fu5AH rat hepatoma cells. During a 24-hour incubation, LUVs of palmitoyl-oleoyl phosphatidylcholine at 1 mg phospholipid (PL) per milliliter extracted approximately 20% of cellular unesterified cholesterol (UC) label and mass in a slow, continuous fashion (half-time t1/2 for UC efflux was approximately 50 hours) and human HDL3 at 25 micrograms PL per milliliter extracted approximately 15% cellular UC label with no change in cellular cholesterol mass (t1/2 of approximately 8 hours). In contrast, the combination of LUVs and HDL3 extracted over 90% of UC label (t1/2 of approximately 4 hours) and approximately 50% of the UC mass, indicating synergy. To explain this synergy, specific particle interactions were examined, namely, remodeling, in which the two acceptors alter each other's composition and thus the ability to mobilize cellular cholesterol, and shuttling, in which the small acceptor ferries cholesterol from cells to the large acceptor. To examine remodeling, LUVs and HDL were coincubated and reisolated before application to cells. This HDL became UC depleted, PL enriched, and lost a small amount of apolipoprotein A-I. Compared with equivalent numbers of control HDL particles; remodeled HDL caused faster efflux (t1/2 approximately 4 hours) and exhibited a greater capacity to sequester cellular cholesterol over 24 hours (approximately 38% versus approximately 15% for control HDL), consistent with their enrichment in PL. Remodeled LUVs still extracted approximately 20% of cellular UC. Thus, remodeling accounted for some but not all of the synergy between LUVs and HDL. To examine shuttling, several approaches were used. First, reisolation of particles after an 8-hour exposure to cells revealed that HDL contained very little of the cellular UC label. The label was found almost entirely with the LUVs, suggesting that LUVs continuously stripped the HDL of cellular UC. Second, bidirectional flux studies demonstrated that LUVs blocked the influx of HDL UC label into cells, while the rate of efflux of cellular UC was maintained. These kinetic effects explained the massive net loss of cellular UC to LUVs with HDL. Third, cyclodextrin, an artificial small acceptor that does not acquire PL and hence does not become remodeled, exhibited substantial synergy with LUVs, supporting shuttling. Thus, the presence of large and small acceptors together can overcome intrinsic deficiencies in each. Small acceptors are efficient at extracting cellular cholesterol because they approach cell surfaces easily but have a low capacity, whereas large acceptors are inefficient but have a high capacity. When present simultaneously, where the small acceptor can transfer cholesterol quickly to the large acceptor, high efficiency and high capacity are achieved. The processes responsible for this synergy, namely, remodeling and shuttling, may be general phenomena allowing cooperation both during normal physiology and after therapeutic administration of acceptors to accelerate tissue cholesterol efflux in vivo. |
| Remodeling of HDL containing apoA-I but not apoA-II (LpA-I) by lipoprotein-deficient plasma and hepatic lipase: its effect on the structure and cellular cholesterol-reducing capacity of LpA-I Ohta, T., Y. Ikeda, et al. (1996), Biochim Biophys Acta 1303(2): 137-44. Abstract: We investigated the effects of lipoprotein-deficient plasma (LDP) and hepatic lipase (HL) on the structure and cellular cholesterol-reducing capacity of subclasses of LpA-I (HDL containing apoA-I but not apoA-II). LpA-I is composed of large (11.1 nm; L-LpA-I), medium (8.8 nm: M-LpA-I) and small (7.7 nm: S-LpA-I) particles. L-LpA-I and M- and S-LpA-I combined (MS-LpA-I) were incubated with lipoprotein-deficient plasma and HL in the presence of very low density lipoprotein (VLDL). After incubation of L-LpA-I, the proportions of cholesteryl esters and phospholipids decreased and as a result, the proportion of protein increased. The remodeled L-LpA-I particles were generally smaller (spherical: 7.8-8.8 nm) in diameter. A small number of disc-shaped particles were also found in electron photomicrographs. These changes coincided with a slower electrophoretic mobility of remodeled L-LpA-I. In the case of MS-LpA-I, only the proportion of free cholesterol increased after incubation, and MS-LpA-I particles did not change in size. The cholesterol-reducing capacities of remodeled L-LpA-I and MS-LpA-I from macrophage foam cell were slightly higher and lower than their respective original counterparts, although neither of these differences was statistically significant. These results suggest that LDP and HL mainly contribute to the remodeling of L-LpA-I particles, and may not affect the cellular cholesterol-reducing capacity of these particles. |
| Removal of cellular cholesterol by pre-beta-HDL involves plasma membrane microsolubilization Gillotte, K. L., W. S. Davidson, et al. (1998), J Lipid Res 39(10): 1918-28. Abstract: High density lipoprotein (HDL) is able to remove unesterified cholesterol from peripheral cells in the process of reverse cholesterol transport by an aqueous diffusion mechanism as well as by an apolipoprotein (apo)-mediated process. The aqueous diffusion mechanism is understood but the molecular mechanism of lipid-poor pre-beta-HDL-(apo-) mediated cholesterol removal is not known. Measurements of the initial rates of efflux of unesterified cholesterol and phospholipid from human fibroblasts to lipid-free, human apoA-I showed that both lipids are released from the cells during a 10-min incubation with apoA-I. The concentration-dependence of efflux of the lipids is the same (Km = 0.4 and 0.6 microg apoA-I/ml for cholesterol and phospholipid flux, respectively), suggesting a membrane microsolubilization process. A finite pool of about 1% of the plasma membrane cholesterol is accessible for release by solubilization; the limited size of this cholesterol pool is not due to a lack of availability of apoA-I, but rather to the restricted amount of phospholipid that is removed from the plasma membrane. Plasma membrane domains may be involved in membrane microsolubilization, but caveolar cholesterol seems not to be specifically accessed in this process. Membrane microsolubilization is the process by which pre-beta1-HDL removes cell cholesterol in the first step of reverse cholesterol transport. When apoA-I is present in the extracellular space, the relative contributions of cholesterol efflux by membrane microsolubilization and by aqueous diffusion are determined by the degree of lipidation of the apoA-I molecules. |
| Removal of cholesterol from Cheddar cheese by beta-cyclodextrin Kwak, H. S., C. S. Jung, et al. (2002), J Agric Food Chem 50(25): 7293-8. Abstract: This study was carried out to determine the cholesterol removal rate and resulting changes in flavor, fatty acid and bitter amino acid production in reduced-cholesterol Cheddar cheese, made by cream separation followed by 10% beta-cyclodextrin (beta-CD) treatment. The cholesterol removal from the cheese was 92.1%. The production of short-chain free fatty acids (FFAs) increased the ripening time in control and cream-treated cheeses. The quantity of short-chain FFAs released between treatments during ripening was different, while not much difference was found in the production of neutral volatile compounds in the samples. Reduced-cholesterol cheese produced much higher levels of bitter amino acids than the control. In sensory analysis, the texture score of control Cheddar cheese increased significantly with ripening time; however, that of the cream treatment group decreased dramatically with ripening time. On the basis of our results, we conclude that the cheese made from beta-CD-treated cream had a higher rate of cholesterol removal and ripened rapidly. |
| Removal of cholesterol from extrahepatic sources by oxidative mechanisms Bjorkhem, I., U. Diczfalusy, et al. (1999), Curr Opin Lipidol 10(2): 161-5. Abstract: Sterol 27-hydroxylase is an evolutionarily old cytochrome P450 species that is critical for oxidation of the side chain of cholesterol in connection with bile acid biosynthesis in the liver. The wide tissue and organ distribution of the enzyme suggests that it may also have other functions. It was recently shown that some cells (e.g. macrophages) have a high capacity to convert cholesterol into both 27-hydroxycholesterol and cholestenoic acid and that there is a significant flux of these steroids from extrahepatic sources to the liver where they are further oxidized into bile acids. The magnitude of this flux is such that it may be of importance for overall homeostasis of cholesterol. Very recently it was shown that the brain utilizes a similar mechanism for removal of cholesterol. A unique brain-specific 24S-hydroxylase converts cholesterol into 24S-hydroxycholesterol that is transported over the blood-brain barrier much more rapidly than unmetabolized cholestero. When 24S-hydroxycholesterol has reached the circulation it is taken up by the liver and further metabolized, most probably into bile acids. This flux is likely to be of importance for cholesterol homeostasis in the brain. This review summarizes our current knowledge regarding oxidative mechanisms for removal of extrahepatic cholesterol. It is evident that some cells utilize these mechanisms as alternatives or complements to the classical HDL-dependent reverse cholesterol transport. |
| Removal of cholesterol from the cells--a new solution to fat diseases? Ikonen, E. (2000), Duodecim 116(5): 465-6. |