Transfer Of Esterified Cholesterol Research Articles

The Role of Exercise-Based Cardiac Rehabilitation After Myocardial Infarction on Cholesterol Transfer to HDL.

High-density lipoprotein (HDL) is associated with decreased incidence of cardiovascular events, and its functionality also influences prognosis. Exercise is an important tool to improve prognosis in the post-infarction (MI) population, but the role of exercise on HDL functionality is poorly understood. Sixty-two patients with acute MI were randomized in a supervised exercise program for 12-14 weeks (exercise group-EG) or a control group (CG). The main objective of the study was to analyze the role of exercise on esterified cholesterol (EC) and unesterified cholesterol (UC) transfer to HDL. For the total population, the baseline mean rate of EC transfer to HDL was 2.53 ± 0.83 and at the end of follow-up, it was 2.74 ± 0.64 (p = 0.03). The figures for UC were, respectively, 4.08 ± 1.2 and 4.4 ± 1.06 (p = 0.02). The difference (follow-up minus baseline) for EC was 0.15 ± 0.84 for the control group and 0.27 ± 0.69 for the exercise group (p = 0.53); for UC, the figures were 0.28 ± 1.14 and 0.35 ± 0.96 (p = 0.80), respectively, for the control and exercise groups. In post-MI patients, 12-14 weeks of supervised exercise did not improve HDL functionality.

Regular Practice of Physical Activity Improves Cholesterol Transfers to High-Density Lipoprotein (HDL) and Other HDL Metabolic Parameters in Older Adults

The effects of regular physical activity on two important anti-atherosclerosis functions of high-density lipoprotein (HDL), namely its capacity to receive both forms of cholesterol and its anti-oxidant function, were investigated in this study comparing older adults with young individuals. One-hundred and eight healthy adult individuals were enrolled and separated into the following groups: active older (60–80 yrs, n = 24); inactive older (60–79 yrs, n = 21); active young (20–34 yrs, n = 39); and inactive young (20–35 yrs, n = 24). All performed cardiopulmonary tests. Blood samples were collected in order to assess the following measures: lipid profile, HDL anti-oxidant capacity, paraoxonase-1 activity, HDL subfractions, and lipid transfer to HDL. Comparing active older and active young groups with inactive older and inactive young groups, respectively, the active groups presented higher HDL-C levels (p < 0.01 for both comparisons), unesterified cholesterol transfer (p < 0.01, p < 0.05), and intermediate and larger HDL subfractions (p < 0.001, p < 0.01) than the respective inactive groups. In addition, the active young group showed higher esterified cholesterol transfer than the inactive young group (p < 0.05). As expected, the two active groups had higher VO2peak than the inactive groups; VO2peak was higher in the two younger than in the two older groups (p < 0.05). No differences in unesterified and esterified cholesterol transfers and HDL subfractions were found between active young and active older groups. HDL anti-oxidant capacity and paraoxonase-1 activity were equal in all four study groups. Our data highlight and strengthen the benefits of regular practice of physical activity on an important HDL function, the capacity of HDL to receive cholesterol, despite the age-dependent decrease in VO2peak.

Hydroxychloroquine increased cholesterol transfer to high-density lipoprotein in systemic lupus erythematosus: A possible mechanism for the reversal of atherosclerosis in the disease.

The beneficial effect of hydroxychloroquine (HCQ) in decreasing LDL levels on Systemic Lupus Erythematosus (SLE) is well defined. The influence of this drug on HDL levels is still under debate and information about its effect on cholesterol reverse transport is lacking. To evaluate the effects of HCQ on HDL levels and the transfer of lipids to this lipoprotein in SLE. Nineteen SLE patients using only HCQ (SLE WITH HCQ), 19 SLE patients without any therapy (SLE WITHOUT THERAPY), and 19 healthy controls (CONTROL) were included. All three groups were premenopausal women age- and gender-matched. Serum lipids and apolipoproteins were determined by commercial kits. An in vitro transfer of four lipids (14C-Phospolipid, 3H-Cholesteryl ester, 3H-Triglyceride, and 14C-Unesterified cholesterol) from a radioactively labeled nanoemulsion donor to HDL was performed in all participants. Groups had comparable mean age, weight, height, BMI(body mass index), and waist circumference (p > .05). Mean HDL levels were higher in SLE WITH HCQ group compared to SLE WITHOUT THERAPY(58.37 ± 14.04 vs 49.79 ± 8.0mg/dL; p < .05) but lower than CONTROL (58.37 ± 14.04 vs 68.58 ± 9.99mg/dL; p < .05). Total cholesterol (TC) and LDL levels were also significantly lower in SLE WITH HCQ compared SLE WITHOUT THERAPY(148.16 ± 16.43 vs 167.11 ± 30.18mg/dL; p < .05, 75.05 ± 22.52 vs 96.05 ± 25.63mg/dL; p < .05) and CONTROL (148.16 ± 16.43 vs 174.11 ± 23.70mg/dL; p < .05, 75.05 ± 22.52 vs 88.53 ± 20.24mg/dL; p < .05). The in vitro lipid transfer to HDL study revealed a significant difference among the three groups (p = .002) with a higher transfer of unesterified cholesterol(UC) in SLE WITH HCQ compared to SLE WITHOUT THERAPY(5.40 ± 1.05% vs. 4.44 ± 1.05%; p < .05). The latter was significantly decreased compared to CONTROL (5.40 ± 1.05% vs. 5.99 ± 1.71%; p < .05).The percentages of transfer of triacylglycerol (4.93 ± 0.69% vs. 4.50 ± 0.69% vs. 5.14 ± 1.01%; p = .054), esterified cholesterol (5.24 ± 0.70% vs. 4.96 ± 0.89% vs. 5.69 ± 1.27%; p = .079), and phospholipid (15.67 ± 1.03% vs. 15.34 ± 1.44% vs. 16.47 ± 1.89%; p = .066) were similar among groups. The present study is the first to demonstrate that HCQ promoted a higher transfer of unesterified cholesterol which may account for the increased HDL levels in lupus patients under HCQ. This desirable effect may underlie the reported reduced atherosclerosis in SLE.

Abstract P147: Association Between Lipid Transfer To HDL-c And Arterial Stiffness In Patients With Ischemic Stroke Due To Hypertensive Emergency

Objective: To evaluate arterial stiffness (AS) and lipids transfer to high density lipoprotein cholesterol (HDL-c) in ischemic stroke due to hypertensive emergency (IS-HE). Methods: Thirty and one patients with IS-HE, 33 individuals with ischemic stroke without hypertensive emergency (IS), 31 controlled hypertensive (CHT) and 33 normotensive (NT) individuals were studied. AS was assessed by analyzing the pulse wave velocity (PWV), augmentation index and central blood pressure. The lipids transfer to HDL-c was evaluated after incubation of the plasma with an artificial radiolabeled nanoparticle, used as a donor of esterified and non-esterified cholesterol. Cholesterol transfer was measured in the HDL-c fraction, after chemical precipitation of lipoproteins containing apolipoprotein B. Results: Systolic (SBP) and diastolic (DBP) blood pressure were significantly higher in the IS-HE compared to IS, CHT and NT groups (190/110 mmHg vs 140/87, 128/69 and 129/80 mmHg, respectively; p&lt;0.05). Similarly, central SBP and DBP were higher in patients with IS-HE compared to IS, CHT and NT (147/101 mmHg vs 128/90, 118/71 and 120/83 mmHg, respectively; p&lt;0.05). PWV was significantly higher in the groups IS-HE and IS, compared to NT group (9.7 and 10.6 vs 7.8 m/s, respectively; p&lt;0.05). The esterified cholesterol transfer was reduced in the IS-HE and IS groups in relation to the CHT and NT groups (4.19 and 3.76 vs 4.5 and 4.75, respectively; p&lt;0.05). The non-esterified cholesterol transfer was also markedly decreased in IS-HE e IS groups compared to CHT and NT groups (4.57 and 4.06 vs 5.47 and 5.71, respectively; p&lt;0.05). A negative correlation was observed between non-esterified cholesterol transfer and PWV in the IS-HE group. Conclusion: This study provides evidence that high blood pressure levels are associated to arterial stiffness and a marked decrease in the lipids transfer to HDL-c in patients with ischemic stroke due to hypertensive emergency, which indicates that changes in the HDL-c fraction can contribute to atherogenesis in these patients. These considerations contribute to the concept that determining HDL-c functionality with dynamic assays can be relevant for predicting the cardiovascular disease risk.

Effect of caloric restriction and statins on the process of cholesterol transfer to HDL in women with premature CAD

Abstract Introduction Transfer of cholesterol to HDL from the other lipoprotein classes has an important role in HDL metabolism and function. Patients with premature CAD showed reduced rates of cholesterol transfer, which was not dependent on HDL-cholesterol levels. The effects of statin treatment and caloric restriction on anti-atherogenic properties of HDL, which are critical issues in CAD prevention, have been scarcely described. Purpose To evaluate the effect of caloric restriction associated or not with statin use on the transfer of cholesterol to HDL. Methods This randomized study analyzed the functionality of HDL in 26 women, aged ≤55 years, with CAD diagnosed angiographically. Patients were allocated in two groups: caloric restriction (CR) group (n=13) characterized by a diet that reduced 30% of their usual daily caloric intake, and CR plus atorvastatin (CR+A) group (n=13) characterized by the addition of 80 mg of atorvastatin daily to the CR diet. Blood samples were collected before and 60 days after starting interventions for analysis of lipid profile that included apoA-I and B, and to evaluate the anti-atherogenic functionality of HDL by the cholesterol transfer to HDL assay performed in vitro, using artificial donor lipid nanoparticles resembling lipoproteins labeled with radioactive lipids and incubated with total plasma. Results Body mass index reduced in both groups (p&amp;lt;0.01). In the CR group, we observed a tendency of reduction of total cholesterol from 229±55 to 207±59 mg/dL (p=0.07), LDL-C from 143±40 to 129±49 mg/dL (p=0.07) and HDL-C 56±13 to 53±14 mg/dL (p=0.07). Apo B and apo A-I reduced, respectively, from 1.20±0.35 to 1.05±0.36 g/L (p=0.01) and 1.59±0.32 to 1.43±0.28 g/L (p=0.01). In the CR+A group, we observed reduction of total cholesterol from 253±97 to 169±47 mg/dL (p&amp;lt;0.01), LDL-C from 147±57 to 97±39 mg/dL (p&amp;lt;0.01), and apo B from 1.26±0.39 to 0.85±0.22 g/L (p&amp;lt;0.01). HDL-C and apo A-I did not change. In CR group, the transfers of unesterified and esterified cholesterol to HDL did not change. In CR+A group, the percentage of transfer of unesterified cholesterol to HDL increased by almost 10%, from 3.4±0.6% to 3.7±0.7% (p=0.03), but no change in esterified cholesterol transfer. Conclusion CR and atorvastatin treatment was not only beneficial because of LDL-C lowering but also by increasing the transfer of unesterified cholesterol to the HDL fraction, an independent anti-atherogenic mechanism, that may be important in the treatment of women with premature CAD. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001

Abstract P081: Expression Of Micro-rnas And Transfer Of Lipids To HDL In Vitro In Stroke Due To Hypertensive Emergency

Objective: This study evaluates the association of expression of microRNAs (miRNAs) 221/222 and lipid transfer in ischemic stroke (IS) patients due to hypertensive emergency (HE). Methods: Thirty and one patients with IS due to hypertensive emergency (IS-HE), 33 individuals with IS without HE (IS), 31 controlled hypertensive (CHT) and 33 normotensive (NT) individuals were studied. The expression of miRNAs was performed by RT-q PCR (real-time quantitative polymerase chain reaction). The lipid transfer to high density lipoprotein cholesterol (HDLc) was evaluated after incubation of the plasma with an artificial nanoparticle used as a donor of esterified and non-esterified cholesterol, radiolabelled. Cholesterol transfer was measured in the HDLc fraction, after chemical precipitation of lipoproteins containing apolipoprotein B. Results: Systolic and diastolic blood pressure were significantly higher in the IS-HE compared to IS, CT and NT groups (162/99 mmHg vs 140/87, 128/69 and 129/82 mmHg, respectively; p&lt;0.05). The miRNA-221 expression was higher in the IS-HE group compared to the IS, CHT and NT groups (4.23 vs 2.44, 1.35 and 1.05, respectively; p&lt;0.003). MiRNA-222 showed overexpression in the IS-HE and IS groups compared to the CHT group (1.26 and 1.27 vs 0.24, respectively; p&lt;0.0001). The esterified cholesterol transfer was reduced in the IS-HE and IS groups in relation to the CHT and NT groups (4.19 and 3.76 vs 4.5 and 4.75, respectively; p&lt;0.05). Non-esterified cholesterol transfer was decreased in the IS-HE and IS groups compared to CHT and NT groups (4.57 and 4.06 vs 5.47 and 5.71, respectively; p&lt;0.05). There was a negative correlation between miRNA-221 and esterified cholesterol transfer and also with free cholesterol. Conclusions: This study provides evidence of the miRNAs participation in IS-HE, suggesting that the increased expression of miRNAs-221/222 can be a biomarker in cases of IS, mainly associated to HE. In addition, lipid transfer to HDLc is decreased in patients with stroke and hypertensive emergency. This reduction was previously associated with coronary heart disease, but no with stroke. Therefore, HDLc functions can be reduced in ischemic stroke by hypertensive emergency, which can also contribute to atherogenic process.

Acute thermal stress promotes morphological and molecular changes in the heart of broiler chickens

This study aimed to understand the possible effects of acute thermal stress (32ºC, 12 hours) on body temperature using two measurement methods (via probe and rectal), on the morphometric aspects of the heart and aortic artery, on gene expression (superoxide dismutase, glutathione peroxidase-3, nitric oxide synthase, angiotensin-converting enzyme and esterified cholesterol transfer protein), inflammatory parameters (myeloperoxidase and N-acetylglycosaminidase), oxidative stress parameters and nitrite levels in broilers (Cobb 500) at 42 days of age. 36 broilers with 42 days of age were used, distributed in a 2x2 factorial scheme: two thermal environments (comfort at 18ºC and stress at 32ºC) and two methods of measuring body temperature (via probe and rectal). Thermal stress triggered an increase in body temperature regardless of the measurement method. There was a significant effect on the thickness of the aortic artery wall and on the lateral lateral and posterior antero diameters (P &lt;0.05). Likewise, there was a difference in the dosages of lipid hydroperoxides, in the quantification of reactive oxygen species and in the dosage of nitrite (P &lt;0.05). The quantification of the mRNA of the induced nitric oxide synthase, angiotensin-converting enzyme and esterified cholesterol transfer protein genes were significantly higher in animals subjected to heat stress. Thus, it can be concluded that acute thermal stress was able to promote several morphological and molecular changes in the heart and aorta artery of broilers.

Androgen deprivation therapy improves the in vitro capacity of high-density lipoprotein (HDL) to receive cholesterol and other lipids in patients with prostate carcinoma

BackgroundAndrogen deprivation therapy (ADT) is widely used in the treatment of testosterone-dependent prostate carcinomas. ADT often increases plasma LDL and HDL cholesterol and triglycerides. The aim was to test whether ADT changes the transfer of lipids to HDL, an important aspect of this metabolism and HDL protective functions, and related parameters.MethodsSixteen volunteers with advanced prostate carcinoma submitted to pharmacological ADT or orchiectomy had plasma collected shortly before and after 6 months of ADT. In vitro transfer of lipids to HDL was performed by incubating plasma with donor emulsion containing radioactive lipids by 1 h at 37 °C. After chemical precipitation of apolipoprotein B-containing lipoprotein, the radioactivity of HDL fraction was counted.ResultsADT reduced testosterone to nearly undetectable levels and markedly diminished PSA. ADT increased the body weight but glycemia, triglycerides, LDL and HDL cholesterol, HDL lipid composition and CETP concentration were unchanged. However, ADT increased the plasma unesterified cholesterol concentration (48 ± 12 vs 56 ± 12 mg/dL, p = 0.019) and LCAT concentration (7.15 ± 1.81 vs 8.01 ± 1.55μg/mL, p = 0.020). Transfer of unesterified (7.32 ± 1.09 vs 8.18 ± 1.52%, p < 0.05) and esterified cholesterol (6.15 ± 0.69 vs 6.94 ± 1.29%, p < 0.01) and of triglycerides (6.37 ± 0.43 vs 7.18 ± 0.91%, p < 0.001) to HDL were increased after ADT. Phospholipid transfer was unchanged.ConclusionIncrease in transfer of unesterified and esterified cholesterol protects against cardiovascular disease, as shown previously, and increased LCAT favors cholesterol esterification and facilitates the reverse cholesterol transport. Thus, our results suggest that ADT may offer anti-atherosclerosis protection by improving HDL functional properties. This could counteract, at least partially, the eventual worse effects on plasma lipids.

Subclinical Hyperthyroidism: Status of the Cholesterol Transfers to HDL and Other Parameters Related to Lipoprotein Metabolism in Patients Submitted to Thyroidectomy for Thyroid Cancer.

Purpose: Lipid metabolism has been poorly explored in subclinical hyperthyroidism. The aim was to examine the effects of exogenous subclinical hyperthyroidism in women under levothyroxine treatment upon plasma lipids and aspects of HDL metabolism.Methodology: Ten women were studied in euthyroidism and again in exogenous subclinical hyperthyroidism. Thyroid function tests and plasma lipids were studied.Results: HDL-cholesterol (increased 21.6%, p = 0.0004), unesterified cholesterol (increased 12.3%, p = 0.04) and Lp(a) (increased 33,3%, P = 0.02) plasma concentrations were higher in subclinical hyperthyroidism compared to euthyroidism, but total cholesterol, LDL, non-HDL cholesterol, triglycerides, apo A-I, apo B were unchanged. PON1 activity (decreased 75%, p = 0.0006) was lower in subclinical hyperthyroidism. There were no changes in HDL particle size, CETP and LCAT concentrations. The in vitro assay that estimates the lipid transfers to HDL showed that esterified cholesterol (increased 7.1%, p = 0.03), unesterified cholesterol (increased 7.8%, p = 0.02) and triglycerides (increased 6.8%, p = 0.006) transfers were higher in subclinical hyperthyroidism. There were no changes in phospholipid transfers to HDL in subclinical hyperthyroidism.Conclusions: Several alterations in the plasma lipid metabolism were observed in the subclinical hyperthyroidism state that highlight the importance of this aspect in the follow-up of those patients. The increase in HDL-C and in the transfer of unesterified and esterified cholesterol to HDL, an important anti-atherogenic HDL function are consistently protective for cardiovascular health. The increase in Lp(a) and the decrease in PON-1 activity that are important risk factors were documented here in subclinical hyperthyroidism and these results should be confirmed in larger studies due to great data variation but should not be neglected in the follow-up of those patients.

Aerobic Training in Young Men Increases the Transfer of Cholesterol to High Density Lipoprotein In Vitro: Impact of High Density Lipoprotein Size.

Exercise training not only improves the plasma lipid profile but also reduces risk of developing coronary heart disease. We investigate whether plasma lipids and high density lipoprotein (HDL) metabolism are affected by aerobic training and whether the high-density lipoprotein cholesterol (HDL-C) levels at baseline influence exercise-induced changes in HDL. Seventy-one male sedentary volunteers were evaluated and allocated in two subgroups, according to the HLD-C levels (< or >40 mg/dL). Participants underwent an 18-week aerobic training period. Blood was sampled before and after training for biochemical analysis. Plasma lipids, apolipoproteins, HDL diameter, and VO2 peak were determined. Lipid transfers to HDL were determined in vitro by incubating plasma samples with a donor lipid artificial nanoemulsion. After the 18-week period of aerobic training, the VO2 peak increased, while the mean body mass index (BMI) decreased. HDL-C concentration was higher after the training period, but low-density lipoprotein cholesterol (LDL-C) and non-HDL-C did not change. The transfer of esterified cholesterol and phospholipids was greater after exercise training, but the triacylglycerol and unesterified cholesterol transfers were unchanged. The HDL particle diameter increased after aerobic training in all participants. When the participants were separated in low-HDL and normal-HDL groups, the postaerobic exercise increment in HDL-C was higher in the low-HDL group, while the transfer of esterified cholesterol was lower. In conclusion, aerobic exercise training increases the lipid transfers to HDL, as measured by an in vitro method, which possibly contributes to the classical elevation of the HDL-C associated with training.

HDL acceptor capacities for cholesterol efflux from macrophages and lipid transfer are both acutely reduced after myocardial infarction

BackgroundThe transport of lipids from the artery wall is one of the most essential anti-atherogenic functions of high-density lipoprotein (HDL). Recent reports of changes in the HDL composition, during myocardial infarction (MI), suggest that this function may be altered. MethodsForty-one consecutive patients with ST-segment elevation MI enrolled at the Brasilia Heart Study were selected. The following HDL-related measures were determined upon admission (D1) and on the fifth day (D5) after MI: C-reactive protein, CETP and PLTP activity, HDL composition, efflux of cholesterol from J774 macrophages to HDL, and transfer of unesterified and esterified cholesterol, triglycerides and phospholipids from a donor nanoemulsion to HDL. ResultsFrom D1 to D5, the activity of CETP decreased by 25%, but PLTP activity remained unchanged. Esterified cholesterol (−23%) and phospholipid (−9.5%) contents of HDL decreased. Transfer of triglycerides (−36.5%) and esterified cholesterol (−14.7%) to HDL from nanoemulsions was reduced, but other lipids transfers were unchanged. Cholesterol efflux to HDL was also diminished by 8.5% (p=0.04) on D5 compared to D1. It was more pronounced in patients above the 75th percentile of C-reactive protein. ConclusionsAfter an MI, a simultaneous decrease in lipid transfer to HDL and in the capacity of HDL to efflux cholesterol from cells occurs. Thus, HDL with inferior atheroprotective properties may be generated in the acute post-MI period.

Cooperation between hepatic cholesteryl ester hydrolase and scavenger receptor BI for hydrolysis of HDL-CE

Liver is the sole organ responsible for the final elimination of cholesterol from the body either as biliary cholesterol or bile acids. High density lipoprotein (HDL)-derived cholesterol is the major source of biliary sterols and represents a mechanism for the removal of cholesterol from peripheral tissues including artery wall-associated macrophage foam cells. Via selective uptake through scavenger receptor BI (SR-BI), HDL-cholesterol is thought to be directly secreted into bile, and HDL cholesteryl esters (HDL-CEs) enter the hepatic metabolic pool and need to be hydrolyzed prior to conversion to bile acids. However, the identity of hepatic CE hydrolase (CEH) as well as the role of SR-BI in bile acid synthesis remains elusive. In this study we examined the role of human hepatic CEH (CES1) in facilitating hydrolysis of SR-BI-delivered HDL-CEs. Over-expression of CEH led to increased hydrolysis of HDL-[³H]CE in primary hepatocytes and SR-BI expression was required for this process. Intracellular CEH associated with BODIPY-CE delivered by selective uptake via SR-BI. CEH and SR-BI expression enhanced the movement of [³H]label from HDL-[³H]CE to bile acids in vitro and in vivo. Taken together, these studies demonstrate that SR-BI-delivered HDL-CEs are hydrolyzed by hepatic CEH and utilized for bile acid synthesis.

Lipoprotein metabolism in patients with type 1 diabetes under intensive insulin treatment

BackgroundType 1 diabetes (T1DM) is frequently accompanied by dyslipidemia related with insulin-dependent steps of the intravascular lipoprotein metabolism. T1DM dyslipidemia may predispose to precocious cardiovascular disease and the lipid status in T1DM under intensive insulin treatment has not been sufficiently explored. The aim was to investigate the plasma lipids and the metabolism of LDL and HDL in insulin-treated T1DM patients with high glycemic levels.MethodsSixteen male patients with T1DM (26 ± 7 yrs) with glycated hemoglobin >7%, and 15 control subjects (28 ± 6 yrs) were injected with a lipid nanoemulsion (LDE) resembling LDL and labeled with 14C-cholesteryl ester and 3H-free-cholesterol for determination of fractional clearance rates (FCR, in h-1) and cholesterol esterification kinetics. Transfer of labeled lipids from LDE to HDL was assayed in vitro.ResultsLDL-cholesterol (83 ± 15 vs 100 ± 29 mg/dl, p=0.08) tended to be lower in T1DM than in controls; HDL-cholesterol and triglycerides were equal. LDE marker 14C-cholesteryl ester was removed faster from plasma in T1DM patients than in controls (FCR=0.059 ± 0.022 vs 0.039 ± 0.022h-1, p=0.019), which may account for their lower LDL-cholesterol levels. Cholesterol esterification kinetics and transfer of non-esterified and esterified cholesterol, phospholipids and triglycerides from LDE to HDL were also equal.ConclusionT1DM patients under intensive insulin treatment but with poor glycemic control had lower LDL-cholesterol with higher LDE plasma clearance, indicating that LDL plasma removal was even more efficient than in controls. Furthermore, HDL-cholesterol and triglycerides, cholesterol esterification and transfer of lipids to HDL, an important step in reverse cholesterol transport, were all normal. Coexistence of high glycemia levels with normal intravascular lipid metabolism may be related to differences in exogenous insulin bioavailabity and different insulin mechanisms of action on glucose and lipids. Those findings may have important implications for prevention of macrovascular disease by intensive insulin treatment.

Lipid Transfer to HDL is Higher in Marathon Runners than in Sedentary Subjects, but is Acutely Inhibited During the Run

Although exercise increases HDL-cholesterol, exercise-induced changes in HDL metabolism have been little explored. Lipid transfer to HDL is essential for HDL's role in reverse cholesterol transport. We investigated the effects of acute exhaustive exercise on lipid transfer to HDL. We compared plasma lipid, apolipoprotein and cytokine levels and in vitro transfer of four lipids from a radioactively labeled lipid donor nanoemulsion to HDL in sedentary individuals (n=28) and in marathon runners (n=14) at baseline, immediately after and 72h after a marathon. While HDL-cholesterol concentrations and apo A1 levels were higher in marathon runners, LDL-cholesterol, apo B and triacylglycerol levels were similar in both groups. Transfers of non-esterified cholesterol [6.8 (5.7-7.2) vs. 5.2 (4.5-6), p=0.001], phospholipids [21.7 (20.4-22.2) vs. 8.2 (7.7-8.9), p=0.0001] and triacylglycerol [3.7 (3.1-4) vs. 1.3 (0.8-1.7), p=0.0001] were higher in marathon runners, but esterified-cholesterol transfer was similar. Immediately after the marathon, LDL- and HDL-cholesterol concentrations and apo A1 levels were unchanged, but apo B and triacylglycerol levels increased. Lipid transfer of non-esterified cholesterol [6.8 (5.7-7.2) vs. 5.8 (4.9-6.6), p=0.0001], phospholipids [21.7 (20.4-22.2) vs. 19.1 (18.6-19.3), p=0.0001], esterified-cholesterol [3.2 (2.2-3.8) vs. 2.3 (2-2.9), p=0.02] and triacylglycerol [3.7 (3.1-4) vs. 2.6 (2.1-2.8), p=0.0001] to HDL were all reduced immediately after the marathon but returned to baseline 72h later. Running a marathon increased IL-6 and TNF-α levels, but after 72h these values returned to baseline. Lipid transfer, except esterified-cholesterol transfer, was higher in marathon runners than in sedentary individuals, but the marathon itself acutely inhibited lipid transfer. In light of these novel observations, further study is required to clarify how these metabolic changes can influence HDL composition and anti-atherogenic function.

Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance

OBJECTIVE:Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids.METHODS:Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE) labeled with 14C-cholesteryl ester and 3H-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions.RESULTS:The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The 14C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the 3H-free- cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups.CONCLUSION:In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in atherogenic signaling.

Lipid Metabolism in Subclinical Hypothyroidism: Plasma Kinetics of Triglyceride-Rich Lipoproteins and Lipid Transfers to High-Density Lipoprotein Before and After Levothyroxine Treatment

Subclinical hypothyroidism (SCH) has been associated with atherosclerosis, but the abnormalities in plasma lipids that can contribute to atherogenesis are not prominent. The aim of this study was to test the hypothesis that patients with normocholesterolemic, normotriglyceridemic SCH display abnormalities in plasma lipid metabolism not detected in routine laboratory tests including abnormalities in the intravascular metabolism of triglyceride-rich lipoproteins, lipid transfers to high-density lipoprotein (HDL), and paraoxonase 1 activity. The impact of levothyroxine (LT4) treatment and euthyroidism in these parameters was also tested. The study included 12 SCH women and 10 matched controls. Plasma kinetics of an artificial triglyceride-rich emulsion labeled with radioactive triglycerides and cholesteryl esters as well as in vitro transfer of four lipids from an artificial donor nanoemulsion to HDL were determined at baseline in both groups and after 4 months of euthyroidism in the SCH group. Fractional clearance rates of triglycerides (SCH 0.035 ± 0.016 min⁻¹, controls 0.029 ± 0.013 min⁻¹, p = 0.336) and cholesteryl esters (SCH 0.009 ± 0.007 min⁻¹, controls 0.009 ± 0.009 min⁻¹, p = 0.906) were equal in SCH and controls and were unchanged by LT4 treatment and euthyroidism in patients with SCH, suggesting that lipolysis and remnant removal of triglyceride-rich lipoproteins were normal. Transfer of triglycerides to HDL (SCH 3.6 ± 0.48%, controls 4.7 ± 0.63%, p = 0.001) and phospholipids (SCH 16.2 ± 3.58%, controls 21.2 ± 3.32%, p = 0.004) was reduced when compared with controls. After LT4 treatment, transfers increased and achieved normal values. Transfer of free and esterified cholesterol to HDL, HDL particle size, and paraoxonase 1 activity were similar to controls and were unchanged by treatment. Although intravascular metabolism of triglyceride-rich lipoproteins was normal, patients with SCH showed abnormalities in HDL metabolism that were reversed by LT4 treatment and achievement of euthyroidism

Impact of high cholesterol intake on tissue cholesterol content and lipid transfers to high-density lipoprotein

Objective Esterified cholesterol is the storage form of cholesterol in the organism. High-density lipoprotein (HDL), where free cholesterol is transferred from other lipoproteins and tissues, is the main esterification site in plasma. The aim of this study was to investigate how high cholesterol intake changes free/esterified ratios of cholesterol in the plasma, aorta, liver and lipid transfers to HDL. Methods Twenty male Golden Syrian hamsters fed 0.5% cholesterol for 15 wk and 19 controls without cholesterol feeding were sacrificed to determine serum lipids, transfer proteins (cholesteryl ester transfer protein and phospholipid transfer protein), and amount of free and esterified cholesterol in the aorta and liver. In vitro transfer of radioactive free and esterified cholesterol, phospholipids, and triacylglycerols to HDL was performed by incubating whole plasma with an artificial nanoemulsion used as a lipid donor and measuring radioactivity in the HDL fraction after chemical precipitation of non-HDL fractions and of the nanoemulsion. Results Compared with controls, cholesterol-fed animals showed a 137% increase in non-HDL plasma fraction and a 61% increase in HDL ( P < 0.001). The esterified/free cholesterol ratio in non-HDL and HDL fractions did not change. In the aorta, free cholesterol increased 55% and the esterified/free ratio (0.2) decreased. Cholesterol accumulation in the liver was several-fold greater and esterified/free increased (1.3). Cholesterol feeding pronouncedly increased the transfer of free and esterified cholesterol, phospholipids, and triacylglycerols to HDL and cholesteryl ester transfer protein and phospholipid transfer protein activities. Conclusions Free cholesterol is cytotoxic and less stable than esterified cholesterol, and the present data on how the organism responds to high cholesterol intake with respect to esterified/free ratios in the plasma, aorta, liver, and lipid transfers to HDL may have physiopathologic implications.

Alterations in lipid transfer to High-Density Lipoprotein (HDL) and activity of paraoxonase-1 in HIV+ patients

HIV+ patients often develop alterations of the plasma lipids that may implicate in development of premature coronary artery disease. High-density lipoprotein (HDL) has an important role in preventing atherogenesis and the aim of this study was to investigate aspects of HDL function in HIV+ patients. HIV+ patients (n = 48) and healthy control subjects (n = 45) of both sexes with similar age were studied. Twenty-five were not being treated with antiretroviral agents, 13 were under reverse transcriptase inhibitor nucleosidic and non-nucleosidic (NRTI+NNRTI) and 10 were under NRTI + protease inhibitors (NRTI+PI) treatment. Paraoxonase 1 (PON1) activity and the transfer of free and esterified cholesterol, tryglicerides and phospholipids from a lipidic nanoemulsion to HDL were analyzed. In comparison with healthy controls, HIV+ patients presented low PON-1 activity and diminished transfer of free cholesterol and tryglicerides. In contrast, phospholipid transfer was increased in those patients, whereas the transfer of cholesteryl esters was unchanged. NRTI+NNRTI increases the transfer of cholesteryl esters and triglycerides but in NRTI+PI there was no difference in respect to non-treated HIV+ patients. HDL from HIV+ patients has smaller antioxidant properties, as shown by lower PON-1 activity, and the transfer of lipids to this lipoprotein fraction is also altered, suggesting that HDL function is defective in those patients.

Effects of peroxynitrite on plasma components of the reverse cholesterol transport pathway

Elimination of cholesterol from arterial tissue, crucial in limiting atherogenesis, may be achieved via high-density lipoprotein (HDL)-mediated reverse cholesterol transport (RCT); components of this pathway can be modulated by oxidative stress. Here we have examined the relations between cholesterol efflux, esterification and transfer in human plasma treated with the powerfully reactive nitrogen species, peroxynitrite. Cellular cholesterol efflux to whole plasma, or to peroxynitrite-modified HDL 3, was relatively insensitive to peroxynitrite, as was the transfer of esterified cholesterol. However, plasma cholesterol esterification, via lecithin:cholesterol acyltransferase (LCAT), was markedly inhibited, both directly and indirectly, by peroxynitrite treatment, implying inefficient RCT follows HDL sequestration of cellular cholesterol.

Plasma lipoproteins from patients with poorly controlled diabetes mellitus and "in vitro" glycation of lipoproteins enhance the transfer rate of cholesteryl ester from HDL to apo-B-containing lipoproteins.

Alterations in the reverse cholesterol transport system have been described in diabetic mellitus patients in several but not all studies. Furthermore, recently published investigations suggest that a faster "in vitro" transfer rate of cholesteryl ester from high density lipoproteins to apoB-containing lipoproteins could be solely ascribed to variation of the plasma lipoprotein composition and concentration in the diabetic state. The present study analysed the influence of lipoprotein glycation on the cholesteryl ester transfer protein-mediated transfer of esterified cholesterol from high density lipoprotein and its subfractions to lighter density lipoproteins. For this purpose two sets of "in vitro" experiments were carried out utilizing:1) plasma lipoproteins drawn from diabetic and from normal subjects and; 2) normal lipoproteins or partially purified cholesteryl ester transfer protein submitted to "in vitro" glycation. The transfer rate of 14C-cholesteryl ester labelled HDL subfractions to low or very low density lipoproteins was measured in all experiments. After incubations with plasma d > 1.21 g/ml or with purified cholesteryl ester transfer protein, apoB-containing lipoproteins were precipitated with a dextran sulfate/MgCl2 solution. The "in vitro" glycation of the partially purified cholesteryl ester transfer protein, markedly impaired its activity. However, greater transfer rates were observed when lipoproteins from diabetic individuals or the "in vitro" glycated lipoproteins were utilized. This effect was attributed to glycation of the protein component of HDL. In conclusion, lipoprotein glycation elicits an enrichment of the apoB-containing lipoproteins with cholesteryl ester that is likely related to the premature atherosclerosis in patients with poorly controlled diabetes.