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[Oleic acid-induced interstitial lung edema in the dog: comparison of PEEP with high-frequency jet superimposed ZEEP ventilation].

Oleic acid (0.12 ml/kg) was used to induce pulmonary edema in 10 mongrel dogs. To treat the consequent hypoxaemia we used either positive end expiratory pressure (PEEP) ventilation (n = 5) or zero end expiratory pressure ventilation (ZEEP) plus additional high frequency jet support (n = 5). Hypoxaemia, which paralleled the dramatic increase in lung water, was significantly improved (aADO2) by PEEP but not by ZEEP plus jet. Also venous admixture was significantly lowered by PEEP only. Cardiac output and pulmonary arterial pressure in the two groups were not significantly different. This demonstrates that ZEEP plus jet is not superior to PEEP in the case of oleic acid induced edema, though we obtained good clinical results with the former system in the treatment of atelectasis. In addition, histological evaluation of the dog lungs showed emphysematous lung injury by the jet system, which indicates that such a jet system should be used with caution.

Animals↗

Purification and chemical characterisation of the inhibitor of lipid peroxidation from intestinal mucosa.

The antioxidant previously isolated from intestinal mucosa has been subjected to further purification and identification. Although this inhibitor moved as a single spot on thin-layer chromatography in a number of different solvent systems, it proved to be a mixture of free carboxylic acids whose relative composition was similar in different batches. Detailed studies involving the use of high-pressure liquid chromatography, combined gas chromatography-mass spectrometry, high-field 360 MHz proton nuclear magnetic resonance spectroscopy, fast atom bombardment mass spectrometry and other techniques established that the inhibitor was a mixture of carboxylic acids of the following identity and relative composition (the major components comprising 92% of the total fatty acids): palmitic acid, 14.8%; palmitoleic acid, 3.6%; stearic acid, 7.0%; oleic acid, 21.0%; linoleic acid, 27.6% arachidonic acid, 18.0%. Mixtures of authentic fatty acids of the same relative concentration showed inhibition of peroxidation, comparable with the purified inhibitor from intestinal mucosa. A study of the inhibitory activity of the components of the mixture using malonaldehyde estimation, diene conjugation and arachidonic acid estimation showed that the inhibitory activity was due to palmitoleic and oleic acids only, the latter being the major component.

Animals↗

Purification and properties of aortic cholesteryl ester hydrolase.

The enzyme(s) present in acetonedried powder of rat and rabbit aortas, which catalyzes the synthesis and hydrolysis of cholesteryl ester, was purified partially by acid precipitation, acetone fractionation, O-(diethylaminoethyl) cellulose chromatography, and Sephadex G-100 filtration. The synthetic activity was purified by 120-fold (rat) and 140-fold (rabbit). Purification of hydrolytic activity was 90-fold (rat) and 103-fold (rabbit). Cholesteryl ester hydrolase activity was separated from nonspecific esterase by column chromatography. Both synthetic and the hydrolytic activities are apparently the functions of one enzyme. The mol wt of the enzyme was estimated to be 140,000 dalton as determined by Sephadex G-200 gel filtration. The extracts of the acetone-dried powders of aortas of both species contained an inhibitor of synthetic activity. The inhibitor was nondialyzable and was precipitated at pH 5.7. Both activities were found to be fairly nonspecifc with regard to sterol and fatty acids. With oleic acid, the relative rates of sterol ester synthesis were: cholesterol, 100; cholestanol, 94; desmosterol, 35; coprostanol, 24; ergosterol, 20; and beta-sitosterol, 19. Epicholesterol was not esterified. Oleic acid was most active in cholesteryl ester synthesis, the relative rates being: oleic greater than linoleic greater than arachidonic greater than palmitic greater than stearic greater than butyric. The rate of hydrolysis was maximum with cholesteryl linoleate followed by oleate, linolenate, palmitate, stearate, and laurate in decreasing order.

Acetone↗

Influence of eicosapentaenoic acid (20:5, n-3) on secretion of lipoproteins in CaCo-2 cells.

CaCo-2 cells, grown on filter membranes, were used to study the effects of fatty acids on cellular metabolism of triacylglycerol and phospholipids. The rate of triacylglycerol secretion was enhanced more than 2-fold, from 1 to 2 weeks after reaching confluency, in the presence of 0.6 mM fatty acids. Triacylglycerol secretion and oxidation of oleic acid increased 2- and 9-fold, respectively, with this culture system, as compared to cells grown on conventional plastic dishes. Eicosapentaenoic acid (20:5 n-3), when compared to oleic acid, did not reduce formation of triacylglycerol or enhance phospholipid synthesis in CaCo-2 cells during short term (less than 24 h) experiments, when the cells resided on membranes, regardless of what type of radioisotopes were used as precursors in the incubation media. However, the n-3 fatty acid was preferentially incorporated into phosphatidylinositol, lysophosphatidylcholine, and sphingomyelin, as compared to oleic acid. The disappearance from the apical medium and cellular uptake of labeled eicosapentaenoic and oleic acid were similar during incubations up to 24 h, and the metabolism of these fatty acids to acid-soluble materials and CO2 was equal. Light scattering analysis indicated that secreted lipoproteins of density less than 1.006 g/ml were in the same size-range as chylomicrons derived from human plasma. Assessment of secreted apolipoprotein B showed that by incubating CaCo-2 cells with oleic acid, apolipoprotein B levels increased approximately 1.4-fold when compared to cells incubated with eicosapentaenoic acid, whereas the amount of triacylglycerol and size-range of particles were similar for the two fatty acids. Our data indicate that CaCo-2 cells grown on filter membranes exhibit enterocyte-like characteristics with the ability to synthesize and secrete chylomicrons. Eicosapentaenoic acid and oleic acid are absorbed, metabolized, and influence secretion of lipoprotein particles in a similar way, except for some differences in incorporation of the fatty acids into certain phospholipid classes and a reduced secretion of apolipoprotein B. The culture conditions, including time after confluency and cellular support, are critical for the rate of secretion in the presence of eicosapentaenoic acid and oleic acid.

Apolipoproteins B↗

The binding affinity of fatty acid-binding proteins from human, pig and rat liver for different fluorescent fatty acids and other ligands.

1. Two forms of fatty acid-binding proteins (FABPs) were isolated from human, pig and rat liver cytosols by gelfiltration and anion-exchange chromatography. 2. Both forms did not show physicochemical or chemical differences. They had an Mr of about 14.5 kDa for all species. pI Values were 5.8 for both forms of human and pig liver FABP and 6.4 for both forms of rat liver FABP. In contrast to heart FABPs no tryptophan was present in liver FABPs. 3. Liver FABPs show a much higher enhancement of fluorescence at binding of 11-dansylaminoundecanoic acid, 16-anthroyloxy-palmitic acid and 1-pyrene-dodecanoic acid than heart FABPs and additionally a blue shift in excitation and emission wavelengths with the first fatty acid. 4. The bulky side-chain did not affect fatty acid binding since binding constants of liver FABPs were comparable for these fluorescent fatty acids and oleic acid (0.3-0.7 microM). 5. A 1:1 binding stoichiometry was obtained for oleic acid binding with heart and liver FABPs. 6. Liver FABPs have a high binding affinity for C16-C22 saturated and unsaturated fatty acids, palmitoyl-CoA, bromo-substituted fatty acids, POCA, tetradecylglycidic acid and flavaspidic acid. 7. Fatty acid binding could be reduced to less than 50% by arginine modification with 2,3-butadione or by enzymatic degradation of FABPs with trypsin or pronase.

Animals↗

Trypanosoma cruzi oleate desaturase: molecular characterization and comparative analysis in other trypanosomatids.

Trypanosoma cruzi lipids contain a high content of unsaturated fatty acids, primarily oleic acid (C18:1) and linoleic acid (C18:2). Previous data suggest that this parasite is able to convert oleic acid into linoleic acid; humans are not able to do this. Presently, we show that T. cruzi has a gene with high similarity to the delta12 (omega6)-oleate desaturase from plants. Northern blot analysis of the oleate desaturase gene from T. cruzi (OD(Tc)) indicated that this gene is transcribed in epimastigote, amastigote, and trypomastigote forms. Pulsed-field analysis showed that OD(Tc) is located at distinct chromosomal bands on distinct T. cruzi phylogenetic groups. In addition, the chromoblot analysis demonstrated the presence of homologous OD(Tc) genes in several trypanosomatids; namely, Crithidia fasciculata, Herpetomonas megaseliae, Leptomonas seymouri, Trypanosoma freitasi, Trypanosoma rangeli, Trypanosoma lewisi, Blastocrithidia sp., Leishmania amazonensis, Endotrypanum schaudinni, and Trypanosoma conorhini. The native OD(Tc) activity was detected by metabolic labeling and analysis of total fatty acids from epimastigotes and trypomastigotes of T. cruzi, coanomastigotes of C. fasciculata, and promastigotes of L. amazonensis, H. megaseliae, and L. seymouri. The fact that the enzyme oleate desaturase is not present in humans makes it an ideal molecular target for the development of new chemotherapeutic approaches against Chagas disease.

Amino Acid Sequence↗

Differential effects of saturated and monounsaturated fatty acids on postprandial lipemia and incretin responses in healthy subjects.

BACKGROUND: Elevations of postprandial triacylglycerol-rich plasma lipoproteins and suppressions of HDL-cholesterol concentrations are considered potentially atherogenic. Long-term studies have shown beneficial effects of monounsaturated fatty acids (eg, oleic acid) on fasting lipid and lipoprotein concentrations in humans. A direct stimulatory effect of oleic acid on the secretion of glucagon-like peptide 1 (GLP-1) was shown in animal studies. OBJECTIVE: We compared the postprandial responses of glucose, insulin, fatty acids, triacylglycerol, gastric inhibitory polypeptide (GIP), and GLP-1 to test meals rich in saturated and monounsaturated fatty acids. DESIGN: Ten young, lean, healthy persons ingested 3 meals: an energy-free soup consumed with 50 g carbohydrate (control meal), the control meal plus 100 g butter, and the control meal plus 80 g olive oil. Triacylglycerol and retinyl palmitate responses were measured in total plasma, in a chylomicron-rich fraction, and in a chylomicron-poor fraction. RESULTS: No significant differences in glucose, insulin, or fatty acid responses to the 2 fat-rich meals were seen. Plasma triacylglycerol responses were highest after the butter meal, with chylomicron triacylglycerol rising 2.5-5-fold. Retinyl palmitate responses were higher and more prolonged after the butter meal than after the control and olive oil meals, whereas both postprandial HDL-cholesterol concentrations and GLP-1 and GIP responses were higher after the olive oil meal than after the butter meal. CONCLUSIONS: Olive oil induced lower triacylglycerol concentrations and higher HDL-cholesterol concentrations than butter, without eliciting differences in concentrations of glucose, insulin, or fatty acids. Furthermore, olive oil induced higher concentrations of GLP-1 and GIP than did butter, which may point to a relation between fatty acid composition, incretin responses, and triacylglycerol metabolism in the postprandial phase.

Adult↗

The use of sesame oil and other vegetable oils in the inhibition of human colon cancer growth in vitro.

Sesame contains large quantities of the essential polyunsaturated fatty acid (PUFA), linoleic acid, in the form triglycerides. The antineoplastic properties of many PUFAs such as linoleic acid and their metabolites are known. We tested the hypothesis that natural vegetable oils, such as sesame oil and its component linoleic acid, when added to human colon adenocarcinoma cells growing in tissue culture would inhibit their growth and that normal colon cells would not be similarly affected. Three human colon cancer cell lines and one normal human colon cell line were exposed to the following: (1) pure linoleic acid; (2) lipase-digested sesame oil; (3) undigested sesame oil; (4) five additional common vegetable oils; (5) mineral oil. Linoleic acid inhibited the in vitro growth of all three malignant human colon adenocarcinoma cell lines. The normal colon cell line showed dramatically less inhibition of growth. Lipase-digested sesame oil (LDSO) and undigested sesame oil (UDSO) produced greater inhibition of growth of all three malignant colon cell lines than of the normal colon cells. Five other common vegetable oils containing various amounts of PUFAs such as corn, soybean, safflower, olive and coconut oils, all in their lipase-digested form, were found to dramatically inhibit the growth of the HT-29 malignant human colon cell line. Undigested olive and safflower oils also inhibited the HT-29 cells although not as markedly as the lipase-digested oils. Mineral oil did not inhibit the growth of HT-29 cells. Both lauric and palmitic acid, which are saturated fatty acids found in abundance in coconut oil inhibits the HT-29 cells more strongly than linoleic acid, while oleic acid did not inhibit. We conclude that many vegetable oils including sesame contain in vitro antineoplastic properties and that this finding warrants further investigation both in vitro and in vivo to assess their possible chemotherapeutic potential.

Adenocarcinoma↗

Effect of vehicles and enhancers on the in vitro permeation of melatonin through hairless mouse skin.

The effects of vehicles and penetration enhancers on the in vitro permeation of melatonin through dorsal hairless mouse skin were investigated. Propylene glycol laurate (PGL), isopropyl myristate (IPM), propylene glycol monolaurate (PGML) and propylene glycol monocaprylate (PGMC) showed high permeation fluxes and PGL, PGML and PGMC decreased lag time significantly. In both of the binary co-solvents of diethylene glycol monoethyl ether (DGME)-PGL and DGME-IPM, the highest fluxes were achieved at 20% of DGME, which were 10.5 +/- 1.5 and 9.1 +/- 2.4 microg/cm2/h, respectively. Among fatty acids used as a permeation enhancer, capric acid and oleic acid in DGME-PGL (80:20 v/v) showed relatively high enhancing effects. Capric acid also shortened the lag time of melatonin from 2.4 +/- 0.7 to 1.3 +/- 0.2 h. Oleic acid, however, failed to shorten the lag time. Therefore, for effective solution formulations in terms of permeation flux and lag time, capric acid-containing DGME-PGL (80:20 v/v) could be used to enhance the skin permeation of melatonin.

Administration, Cutaneous↗

[Oleic acid-induced PaO2 decrease model for primary screening of drugs for hypoxemia: effects of tranexamic acid and procaterol hydrochloride on the decrease in PaO2].

We constructed an oleic acid (OA)-induced PaO2 decrease model in guinea pigs. We then examined several basic conditions to establish the primary screening model to determine useful drugs for hypoxemia. Hartley strain guinea pigs were anesthetized with pentobarbital (25 mg/kg) and catheterized into the subclavian artery for blood sampling and for measuring blood pressure; they were also catheterized into the subclavian vein for drug administration. Then the animal was immobilized with pancuronium (0.1 mg/kg) and ventilated by a ventilator with room air. The following results were obtained: 1) there were no significant fluctuations of PaO2, PaCO2 and pH throughout the 11 sampling over a 2-hr period. Airway pressure and blood pressure also remained relatively constant. 2) Percentage of decrease in PaO2 by OA (15 microliters/kg) in the hyperventilated group was greater than that in the normally-ventilated group. 3) Increasing doses of 10, 15, 30 and 60 microliters/kg of OA resulted in dose-dependently lower values of PaO2. 4) Tranexamic acid (2 g/kg, i.p.) significantly prevented the decrease in PaO2 at 10 and 15 min after OA (15 microliters/kg) injection. 5) Procaterol hydrochloride (0.1 microgram/kg, i.v.) failed to inhibit the decrease in PaO2 by OA (15 microliters/kg). These results suggest that by using a suitable ventilation and OA dose, this model could be used as a primary screening model of drugs for hypoxemia and that tranexamic acid might be an effective drug for hypoxemia caused by a mechanism by which OA decreases PaO2.

Animals↗

Visualization of oleic acid-induced transdermal diffusion pathways using two-photon fluorescence microscopy.

In a novel application of dual-channel high-speed two-photon fluorescence microscopy, the skin autofluores-cence and the transdermal fluorescent model drug spatial distributions were imaged simultaneously over precisely the same spatial coordinates. The dual channels enable the detection of the fluorescence emission wavelengths characteristic of the endogenous (intrinsic) skin fluorophores, as well as of the rhodamine-based model drug intensity emission at a different wavelength range of the fluorescence emission spectrum. These fluorescent model drugs delineate the oleic acid induced changes in permeant diffusion with respect to the skin structural features over the 0.3 mm by 0.3 mm skin area imaged per skin sample. The dual-channel high-speed two-photon fluorescence microscopy studies presented here provide evidence for the existence of intracorneocyte diffusion in addition to the commonly cited lipid multilamellar transdermal pathway. The image quantification analysis methodology introduced in this paper reveals that intracorneocyte diffusion exists for the hydrophobic (rhodamine B hexyl ester) and for the hydrophilic (sulforhodamine B) model drugs, in the absence of oleic acid chemical enhancer action. The mechanism of oleic acid chemical enhancer action, however, depends on the model drug physicochemical properties, where the oleic acid induces hydrophobic model drug localization to the lipid multilamellar region, while increasing the hydrophilic model drug lipid to corneocyte partitioning.

Biological Transport↗

Mechanical ventilation increases microvascular permeability in oleic acid-injured lungs.

The pulmonary pathology for which a patient receives ventilatory support may increase the risk of developing barotrauma, because an underlying disease process may weaken the vasculature and render the lung more susceptible to damage by mechanical ventilation. We determined the response of isolated young rabbit lungs to mechanical ventilation after oleic acid (OA) injury. New Zealand White rabbits (0.7-1.3 kg) were anesthetized with pentobarbital sodium (30 mg/kg), tracheotomized, and exsanguinated. The heart and lungs were isolated and perfused with autologous blood at a constant flow. The capillary filtration coefficient (Kf,c, in ml.min-1.cmH2O-1.100 g wet wt-1) and pulmonary arterial (Ppa) and venous pressures were determined before and 30 and 60 min after oleic acid administration (OA group; 0.2 ml into the venous reservoir), ventilation alone (Vent group; peak inspiratory pressure = 25 cmH2O), or oleic acid combined with ventilation (OA + Vent group). Ppa transiently increased by 4.21 +/- 0.822 cmH2O after OA administration but then returned to approximately control values. Baseline Kf,c values for OA (0.288 +/- 0.042), Vent (0.296 +/- 0.035), or OA + Vent (0.276 +/- 0.028) groups were not significantly different from each other. Kf,c after either OA administration (0.45 +/- 0.066) or Vent (0.35 +/- 0.75) were not significantly different from each other or from baseline measurements. In the group ventilated after OA administration (OA + Vent), Kf,c (0.883 +/- 0.148) increased significantly from baseline (P less than 0.001) and was significantly different from all other treatment groups. We conclude that the combination of minimal OA injury and ventilation was more deleterious to the lung than either one alone.

Animals↗

Cardiopulmonary effects of oleic acid-induced pulmonary edema and mechanical ventilation.

In order to define the mechanisms whereby cardiac output and arterial oxygen transport are reduced by acute permeability pulmonary edema and by positive end-expiratory pressure (PEEP), hemodynamic, respiratory, and lung water changes were measured in 12 mechanically ventilated dogs prior to the injection of oleic acid and at 1, 2.5, and 4 hr after the injection. Measurements were performed at each interval before and after the addition of 20 cm H2O PEEP. Positive end-expiratory pressure was not continued between measurements. One hour after the oleic acid injection, the lung water content and the pulmonary vascular resistance had increased more than 100% while the right ventricular (RV) volume, RV stroke volume, and PaO2 had decreased more than 35%. Each application of PEEP increased the PaO2 to control levels. However, PEEP also significantly increased the lung water content and pulmonary vascular resistance, and decreased the RV volume and stroke volume by 33%. The extravasation of fluid from the intravascular to the interstitial and alveolar spaces of the lung with oleic acid pulmonary edema is associated with substantial decreases in right ventricular volume and stroke volume and significant increases in the pulmonary vascular resistance. Treatment with 20 cm H2O PEEP further increases the lung water content and pulmonary vascular resistance and substantially reduces the right ventricular volume and stroke volume.

Animals↗

Autoxidation of fatty acid monolayers adsorbed on silica gel: II. Rates and products.

Unsaturated fatty acid monolayers on silica gel have been autoxidized, and the rate of fatty acid disappearance and products obtained from those membrane-like assemblies have been studied. Fatty acid monolayers consisting of pure linoleic acid, linolelaidic acid, and oleic acid were autoxidized at 60 C. The rates of autoxidation of linoleic acid and linolelaidic acid monolayers followed by the disappearance of substrates are considerably faster than that in bulk phase, and the rates conform to apparent first order kinetics. Autoxidation of linoleic and linolelaidic acid monolayers, unlike bulk phase, produced only a small amount of diene conjugation, and the major products formed were identified as 9,10-epoxy and 12,13-epoxyoctadecenoic acid in roughly equal quantities. The epoxidation is stereospecific, with cis and trans olefins giving cis and trans epoxides, respectively. Oleic acid was autoxidized to only a small extent during 27 hr and produced no detectable amount of epoxide.

Adsorption↗

[Enzymatic synthesis of saccharide and saccharide alcohol fatty acid esters].

Conditions for esterification in tert-butanol using fatty acid as acy1 donor and saccharides or saccharide alcohols as acy1 acceptors, immobilized lipase from Candida sp. 1619 as biocatalyst were investigated. Optimal temperature and pH for esterication were 40 degrees C-45 degrees C and 5.5-7.5, respectively. Among the 13 acy1 donors compared, the best ones are the linoleic acid and oleic acid. The similar conversion degree was obtained when using saturated fatty acids with carbon chain length from C8 to C22. Among the 23 saccharides and saccharide alcohols compared, D-fructose, D-Xylose, trehalose, D-sorbitol, xylitol, mannitol isopropyidoneglucofruranose and alpha-methylglucopyranoside showed much higher esterification degree than other acy1 acceptors. In addition, the reaction degree of saccharide alcohols were substantially higher than that of the corresponding saccharides. The conversion was enhanced greatly when the molar ratio of acy1 donor to acy1 acceptor was higher than 2 to 1. In the case of using sorbitol and loeic acid as substrates, the reaction was carried out in 100 ml conical flask and the reaction system consisted of 3.0 mmol oleic acid(0.85 g), 0.2 mmol sorbitol(0.036 g), 3 mL tert-butanol, 30 mg immobilized lipase(600 u), shaken at 40 degrees C. After reaction for 48 h, more than 90% of sorbitol was esterified based on equal molar of substrates. The products were identified TLC as monoester and diester.

Candida↗

[Fatty acid composition of the cervical mucus obtained during ovulation and at the term of pregnancy].

BACKGROUND: Aim of this work is to evaluate the different fatty acid composition of cervical mucus obtained during ovulation and at the term of pregnancy. METHODS: The fatty acid composition in cervical mucus was determined in 14 non pregnant women during expected ovulation (cervical score > 10) and in 12 at term pregnant women. Following extraction, (acidification and transesterification), the identification and quantification of fatty acids was performed by gas-chromatographic analysis, with the aid of a specific software. RESULTS: In both groups of samples, palmitic acid, stearic acid and oleic acid were the prevalent acids comprising more than half of the total amounts. Compared to non pregnant samples, in pregnant cervical mucus, elevated levels of oleic acid were pointed out, while mean levels of miristic acid and stearic acid were lower. In the samples of cervical mucus drew at the term of pregnancy, arachidonic acid levels mean values were higher when the first period of labour was started. CONCLUSIONS: The pregnancy-induced biochemical changes in fatty acid pattern could likely be correlate to the variations of the physiochemical properties and to the physical appearance that cervical mucus undergoes during pregnancy. The elevated levels of arachidonic acid, during the first period of labour, may be correlated with prostaglandin production by intrauterine tissues (amniotic fluid, amnion, chorion, decidua, myometrium) and probably by cervical mucus.

Adult↗

Effects of furosemide versus isolated ultrafiltration on extravascular lung water in oleic acid-induced pulmonary edema.

We studied the effects of no treatment, furosemide treatment, and isolated ultrafiltration on extravascular lung water (ETVL) in mongrel dogs in whom pulmonary edema was induced with oleic acid. In all treatment groups, ETVL was significantly elevated 90 min after oleic acid infusion. At 270 min, we found no difference between nontreatment and furosemide. There was, however, a significant difference between no treatment and ultrafiltration but not between furosemide and ultrafiltration. In spite of observations which suggest that ultrafiltration is of benefit in reducing ETVL, we could not demonstrate superiority of one therapy over another.

Animals↗

Olive oil and the Mediterranean diet.

The high intake of olive oil in the Mediterranean diet contributes to the low intake of saturated fatty acids among populations in Southern Europe and is associated with a low incidence of coronary heart disease. Replacement of saturated fatty acids with oleic acid leads to a reduction in low-density lipoprotein (LDL) cholesterol without decreasing the concentration of high density lipoprotein (HDL) cholesterol. Oleic acid, however, may not be neutral with regards to its effects on risk of thrombosis which may have adverse consequences in populations with established atherosclerosis.

Cholesterol, HDL↗