Chol Groups Research Articles

Robust aortic media adhesion using hydrophobically modified Alaska pollock gelatin-based adhesive for aortic dissections.

Type-A aortic dissection is an acute injury involving the delamination of the aorta at the parts of the aortic media. Aldehyde crosslinker-containing glues have been used to adhere to the media of the dissected aorta before joining an artificial graft. These glues effectively adhere to the aortic media; however, they show low biocompatibility due to the release of aldehyde compounds. In this study, we report innovative adhesives based on hydrophobically modified Alaska pollock gelatin (hm-ApGltn) with different alkyl or cholesteryl (Chol) groups that adhere to the media of the dissected aorta by combining hm-ApGltns with a biocompatible crosslinker, pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate. The modification of alkyl or Chol groups contributed to enhanced adhesion strength between porcine aortic media. The adhesion strength increased with increasing modification ratios of alkyl groups from propanoyl to dodecanoyl groups and then decreased at a modification ratio of ~20 mol %. Porcine aortic media adhered using 7.5Chol-ApGltn adhesive showed stretchability even when expanded and shrunk vertically by 25% at least five times. Hm-ApGltn adhesives subcutaneously injected into the backs of mice showed no severe inflammation and were degraded during the implantation period. These results indicated that hm-ApGltn adhesives have potential applications in type-A aortic dissection.

Identification of Novel m6A-Related Long Non-Coding RNA Signatures for Cholangiocarcinoma Using Integrated Bioinformatics Analyses

Traditional methods used to treat cholangiocarcinoma are less effective, and the identification of new CHOL signature genes can help in the early clinical diagnosis and intervention of cholangiocarcinoma. In this work, we used integrated bioinformatics analysis to find new m6a-associated lncRNA signatures in cholangiocarcinoma. Pearson correlation test was used to identify m6A-lncRNAs by co-expression analysis of m6A-mrna and lncRNAs. we then selected m6A-lncRNAs co-expressed with METTL3 and METTL14 genes and screened for DEm6A-lncRNAs by comparing expression differences. we then used R package of Spearman coefficient correlation analysis to investigate the relevance of m6A-lncrna expression in CHOL. To determine the relative levels of immune cell infiltration, we performed ssGSEA analysis on all samples using the R package, and then we used graphs to illustrate the differences in immune cell infiltration between the CHOL and NC groups. The results of this study will help to identify new CHOL-causing biosignatures, which are important for the early clinical detection and management of CHOL.

Discrepancies in Electrolyte Measurements by Direct and Indirect Ion Selective Electrodes due to Interferences by Proteins and Lipids.

Objectives We aim to report the simultaneous effect of different protein and lipid concentrations on sodium (Na + ) and potassium (K + ) measurement by direct and indirect ion selective electrodes (dISE and iISE) in patient samples. Materials and Methods Na + and K + were measured in 195 serum samples received in the laboratory using iISE by Roche Modular P800 autoanalyzer and using dISE by XI-921 ver. 6.0 Caretium electrolyte analyzer. Serum total protein (TP), cholesterol (Chol), and triglycerides (TG) were measured using conventional photometric methods on Roche Modular P800 autoanalyzer. Differences for each pair of results for Na + (Diff_Na + = [Na + dISE– Na + iISE ]) and K + (Diff_K + = [K + dISE– K + iISE ]) were calculated. Patient subgroups with high, normal, or low TP (< 5, 5–7.9, or ≥ 8 g/dL), Chol (< 150, 150–299, or ≥300 mg/dL), or TG (< 150, 150–299, or ≥300 mg/dL) were compared using analysis of variance. Note that 95% confidence interval of Diff_Na + and Diff_K + were calculated to see the number of samples showing clinically significant differences. Results Diff_Na + ( p = 0.007) and Diff_K + ( p = 0.002) were found significant between samples with normal and high TP. However, effect of TG was not significant. Chol concentration affected Diff_Na + significantly between low versus normal ( p = 0.002), and high versus normal ( p = 0.031) Chol groups. Diff_K + was significant ( p = 0.009) between low versus normal Chol. Clinically relevant disagreement of ≥|5| mmol/L for Na + was observed in high percentage of samples including all subcategories; however, for K + only 3.6% of the total samples showed disagreement of ≥ |0.5| mmol/L. A multivariate regression equation based on fit regression model was also derived. Conclusion Summarily, interchangeable use of electrolyte results from dISE and iISE is not advisable, especially in a setting of hyperproteinemia (≥8 g/dL) or hypercholesterolemia (≥300 mg/dL); more so for Na + .

Fabrication of robust biomimetic coating by integrated physisorption/chemical crosslinking technique

Intrinsic hydrophobicity of polymeric biomedical devices generally causes adverse complications (i.e. thrombosis formation). In this study, biomimetic surface modification is conducted on different hydrophobic substrates (PP, PET and PTFE) by physisorption and subsequent UV induced chemical crosslinking of a ternary methacrylate copolymer bearing phosphorylcholine (PC), cholesteryl (Chol) and azidophenyl (Az) side groups, poly(MPC-co-CMA-co-AzMA) (PMCA). X-ray photoelectron spectrophotometer (XPS), atomic force microscopy (AFM) and water contact angle (WCA) measurements are used to monitor the changes in chemical composition, morphology and wetting behavior of the polymeric substrate surfaces before and after surface modification. The protein adsorption and platelet adhesion experiments are also performed to assess its antifouling properties. The results show that the synergistic contribution of physical anchor of Chol groups and chemical crosslinking of Az moieties leads to the formation of a highly crosslinked cell outer membrane mimetic coating with relatively uniform and dense nano-granular surface textures. The resultant PMCA modified surface exhibits greatly enhanced hydrophilicity due to the enrichment of hydrophilic phosphorylcholine moieties on the outer layer of PMCA coating. Particularly, compared with poly(MPC-co-CMA) (PMC) and poly(MPC-co-AzMA) (PMA) coatings, PMCA coating possesses good surface stability and interfacial adhesion performance. It provides the polymeric substrates with significantly improved antifouling property. The amounts of proteins and platelets adsorbed or adhered on PMCA modified surfaces could be reduced by at least 85% and 97% after incubation for 48 h, respectively. It offers a facile way to fabricate robust antifouling surface for the improvement of the biocompatibility of polymeric biomedical devices.

Lo etnojuvenil. Un análisis sobre el cambio sociocultural entre tsotsiles, tseltales y choles

I study how indigenous youth reconfigure themselves in relation to a new generational understanding of their ethnicity, which is distant from traditional norms represented by “the custom” as practiced in the community. My reflections are based on testimonies which show the ethnic conditions of a new generation of youths, with a different worldview from that of their grandparents and parents, having other values, emotions and life expectations. I used an ethnographic method in which I conducted interviews and informal conversations, made participant observation, and did bibliographic research during seven years. My research brought to light many parallels in youth experience, leading to my coining of the term “Ethnoyouth” to describe commonalities among Tsotsil, Tseltal and Chol groups with whom I worked.

Lo etnojuvenil. Un análisis sobre el cambio sociocultural entre tsotsiles, tseltales y choles

Estudio cómo lo juvenil indígena se reconfigura en tanto nueva etnicidad generacional, de una forma alejada de "la costumbre" comunitaria. Mis reflexiones se basan en relatos que ilustran las condiciones étnicas de los jóvenes en un tiempo nuevo, con una visión diferente a la de sus padres y abuelos, con búsquedas, valores, emociones y expectativas que indican nuevos rumbos. Usé el método etnográfico y realicé entrevistas, conversaciones informales, observación participante y revisión bibliográfica y hemerográfica durante siete años en comunidades tsotsiles, tseltales y choles. Este material develó contenidos transversales de lo etnojuvenil, la nueva categoría analítica que propongo.

The natural olive constituent oleuropein induces nutritional cardioprotection in normal and cholesterol-fed rabbits: comparison with preconditioning.

Ischemic preconditioning, which is mediated by cell signaling molecules, protects the heart from ischemia-reperfusion injury by limiting the infarct size. Oleuropein, the main polyphenolic constituent of olives, reduced the infarct size in normal and cholesterol-fed rabbits when it was administered at a nutritional dose. The aim of the present study was to compare the effects of oleuropein and preconditioning in terms of the cell signaling and metabolism pathways underlying myocardial protection. Rabbits were randomly divided into six groups: the control group received 5 % dextrose for six weeks, the preconditioning group was subjected to two cycles of preconditioning with 5 min ischemia/10 min reperfusion, the O6 group was treated with oleuropein for six weeks, the Chol group was fed a cholesterol-enriched diet and 5 % dextrose for six weeks, and the CholO6 and CholO3 groups were treated with cholesterol and oleuropein for six and three weeks, respectively; oleuropein was dissolved in 5 % dextrose solution and was administered orally at a dose of 20 mg × kg(-1) × day(-1). All animals were subsequently subjected to 30 min myocardial ischemia followed by 10 min of reperfusion. At that time, myocardial biopsies were taken from the ischemic areas for the assessment of oxidative and nitrosative stress biomarkers (malondialdehyde and nitrotyrosine), and determination of phosphorylation of signaling molecules involved in the mechanism of preconditioning (PI3K, Akt, eNOS, AMPK, STAT3). The tissue extracts NMR metabolic profile was recorded and further analyzed by multivariate statistics. Oxidative biomarkers were significantly reduced in the O6, CholO6, and CholO3 groups compared to the control, preconditioning, and Chol groups. Considering the underlying signaling cascade, the phosphorylation of PI3K, Akt, eNOS, AMPK, and STAT-3 was significantly higher in the preconditioning and all oleuropein-treated groups compared to the control and Chol groups. The NMR-based metabonomic study, performed through the analysis of spectroscopic data, depicted differences in the metabolome of the various groups with significant alterations in purine metabolism. In conclusion, the addition of oleuropein to a normal or hypercholesterolemic diet results in a preconditioning-like intracellular effect, eliminating the deleterious consequences of ischemia and hypercholesterolemia, followed by a decrease of oxidative stress biomarkers. This effect is exerted through inducing preconditioning-involved signaling transduction. Nutritional preconditioning may support the low cardiovascular morbidity and mortality associated with the consumption of olive products.

Aggregation behavior in water of amphiphilic diblock copolymers bearing biocompatible phosphorylcholine and cholesteryl groups

Poly(2-(methacryloyloxy)ethyl phosphorylcholine)-block-poly(cholesteryl 6-methacryloyloxyhexanoate) (PMPC82-b-PChMn) copolymers with different PChM block lengths were prepared via reversible addition–fragmentation chain transfer controlled/living radical polymerization using a PMPC-based macro-chain transfer agent. The subscript number and n (=3 and 6) refer to the degree of polymerization of the PMPC and PChM blocks, respectively. PMPC82-b-PChMn cannot dissolve in water directly due to the strong hydrophobic nature of the PChM block. To prepare the aqueous solution, the diblock copolymer was dissolved in an organic solvent and then dialyzed against pure water. These diblock copolymers formed spherical and rod-like micelles in water, depending on the composition of cholesteryl (Chol) group in the polymer. The prepared aggregates were characterized using static light scattering, dynamic light scattering, transmission electron microscopy and fluorescence probe techniques. The characterization results suggest that the morphology of the polymer aggregates can be controlled from spherical to rod-like micelles by increasing the number of Chol groups in the polymer.

Crosslinking liposomes/cells using cholesteryl group-modified tilapia gelatin.

Cholesteryl group-modified tilapia gelatins (Chol-T-Gltns) with various Chol contents from 3 to 69 mol % per amino group of Gltn were prepared for the assembly of liposomes and cells. Liposomes were physically crosslinked by anchoring Chol groups of Chol-T-Gltns into lipid membranes. The resulting liposome gels were enzymatically degraded by addition of collagenase. Liposome gels prepared using Chol-T-Gltn with high Chol content (69Chol-T-Gltn) showed slower enzymatic degradation when compared with gels prepared using Chol-T-Gltn with low Chol content (3Chol-T-Gltn). The hepatocyte cell line HepG2 showed good assembly properties and no cytotoxic effects after addition of 69Chol-T-Gltns. In addition, the number of HepG2 cells increased with concentration of 69Chol-T-Gltns. Therefore, Chol-T-Gltn, particularly, 69Chol-T-Gltn, can be used as an assembling material for liposomes and various cell types. The resulting organization can be applied to various biomedical fields, such as drug delivery systems, tissue engineering and regenerative medicine.

Health-Promoting Effects of Ethylene-Treated Kiwifruit ‘Hayward’ from Conventional and Organic Crops in Rats Fed an Atherogenic Diet

Kiwifruit is a subtropical fruit that is very popular among consumers. Kiwifruit 'Hayward' ( Actinidia deliciosa C.F. Liang et A.R. Ferguson) is an important source of bioactive compounds and possesses high antioxidant capacity, but its value can be changed during ripening. The aim of this study was to compare the levels of total polyphenols (TP), ascorbic acid (AA), and total antioxidant capacities (TACs) of ethylene-treated and nontreated kiwifruits 'Hayward' from conventional and organic farming. The influence of these fruits on lipid profile, TAC, and liver enzymes in plasma of rats fed diets with cholesterol was studied. Ethylene treatment shortened the ripening of kiwifruits. Ethylene-treated kiwifruits from organic farming (OHE) have the highest contents of TP and TAC. The experiment in vivo was performed during 33 days on male Wistar rats (111 ± 5 g), divided into six groups: one without cholesterol, control (C), and five groups with 1% of cholesterol (Chol). Four groups with cholesterol were supplemented with 5% of lyophilized kiwifruits: ethylene treated, organic (Chol/OHE) or conventional (Chol/CHE); and untreated, organic (Chol/OHC) or conventional (Chol/CHC). Cholesterol diets supplemented with kiwifruit influenced the palatability and feed intake, body gain, and FER. Diets containing kiwifruits significantly influenced the decrease of TG (61%), TC (29%), LDL-C (38%), atherogenic index TC/HDL-C (25%), and atherogenic index (AI, 32%), without differences between treatments. A significant increase of TAC in plasma of rats fed kiwifruit was obtained by DPPH (18%), FRAP (55%), and ABTS (55%). Aspartate aminotransferase (AST) activity in serum was significantly lower for all groups with kiwifruit supplementation. Alanine aminotransferase (ALT) was lower only in diet groups supplemented with conventional fruits in comparison with the cholesterol group. Glucose levels were higher in groups with kiwifruit supplementation than in C and Chol groups. Supplementation of Chol groups with organic kiwifruits influenced the prothrombin index and significantly decreased the amount of platelets (PLT) in blood. In conclusion, studied kiwifruit 'Hayward' can be a very good ingredient of the diet, especially for patients suffering from hypercholesterolemia and with other cardiovascular diseases, but not for diabetic patients.

Influence of two cultivars of persimmon on atherosclerosis indices in rats fed cholesterol-containing diets: Investigation in vitro and in vivo

Objective To assess the influence of two persimmon cultivars on some atherosclerosis indices in rats fed cholesterol (Chol)-containing diets. Methods Persimmon cultivars “Fuyu” and “Jiro” as supplementation to rats’ diets were investigated in vitro to compare the contents of their bioactive compounds (polyphenols, flavonoids, flavanols, tannins, carotenoids, and ascorbic acid) and antioxidant potentials. In the in vivo investigation, 36 male Wistar rats were randomly divided into six diet groups, each with six rats: control, control/Fuyu, control/Jiro, Chol, Chol/Fuyu, and Chol/Jiro. During a period of 47 d (42 d of feeding and 5-d adaptation before the experiment) of the trial, rats in the control group were fed a basal diet and two additional control groups (control/Fuyu and control/Jiro) a basal diet plus 5% of lyophilized Fuyu and Jiro, respectively. The Chol, Chol/Fuyu, and Chol/Jiro rat groups were fed a basal diet supplemented with 1% Chol (Chol group) and 1% Chol plus 5% lyophilized Fuyu (Chol/Fuyu group) and plus 5% lyophilized Jiro (Chol/Jiro group), respectively. After completion of the experiment, the rats were anesthetized using Narcotan (halothane) and sacrificed and the atherosclerotic lesions in the aorta were assessed. The obtained results of the investigation of all six groups were compared. Testing of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerols, total cholesterol in the liver, electrophoretic patterns of liver tissue, and three-dimensional fluorescence of serum protein fractions was performed. Results The polyphenols and tannins were significantly higher in the Fuyu cultivar ( P < 0.05). The antioxidant potential of persimmon Fuyu was higher than in the Jiro cultivar, but the difference was significant only according to the 2,2-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assay ( P < 0.05). Supplementation of diets with 5% of the lyophilized Fuyu and Jiro hindered the increase in plasma lipids versus the Chol group (total cholesterol 19.4% and 9.5%, low-density lipoprotein cholesterol 25.6% and 13.1%, respectively, P < 0.05) and hindered the decrease in plasma antioxidant activity versus the Chol group by 40.0% and 16.8% and by 39.6% and 11.3% for the ABTS and 1,1-diphenyl-2-picrylhydrazyl assays, respectively. The atherosclerotic lesions in the aortas of the Chol/Fuyu and Chol/Jiro groups were significantly less than in the Chol group ( P < 0.05). Electrophoresis of the proteins from rats’ liver tissue showed changes in 14-kDa bands after persimmon supplementation. A shift in maximum wavelengths in three-dimensional fluorescence of serum protein fractions after persimmon supplementation was found in comparison with the control group and an increase in fluorescence intensity compared with the Chol groups. Conclusion The contents of polyphenols and tannins were significantly higher in the Fuyu cultivar ( P < 0.05). The antioxidant potentials of Fuyu were higher than those of the Jiro cultivar, but the difference was significant only according to the ABTS assay ( P < 0.05). Supplementation of 5% lyophilized Fuyu and Jiro to diets of rats fed Chol-containing diets 1) hindered the increase in plasma lipids levels and the decrease in plasma antioxidant activity and 2) significantly decreased the atherosclerotic lesions in the aorta ( P < 0.05). Electrophoretic patterns of liver tissue and fluorescence spectra can be used as additional biomarkers for determination of atherosclerosis indices.

Effects of caponization and testosterone implantation on immunity in male chickens

This study examined the effects of caponization using different doses of testosterone (TES) on sexuality, hematology, and immune responses in male chickens. Healthy male chickens were caponized at 12 wk of age and selected at 16 wk of age for a 10-wk experiment. Fifteen intact male and 15 caponized male chickens were assigned to trial 1. In trial 2, ten sham-operated male chickens (sham) and 40 capons (randomly divided into 4 treatments) were implanted with cholesterol (CHOL, 9.24 ± 0.36 mg), low TES (5.88 ± 0.23 mg), medium TES (9.81 ± 0.17 mg), or high TES (16.7 ± 0.24 mg) administered at 16, 20, and 24 wk of age. Results from trial 1 showed caponization decreased the comb length, height and weight, and hematocrit (P < 0.05) and increased the hemagglutination inhibition (HI; 1 wk postchallenge) and hemagglutination titer after Newcastle disease virus (NDV) and SRBC injections (P < 0.05). In trial 2, the medium TES increased the comb length and height as compared with the CHOL group. Only the high TES increased the comb weight (P < 0.05). The HI titer (1 wk postchallenge) in the CHOL group was higher than the sham (P < 0.05). The medium TES decreased the HI titer (P < 0.05) to the level of the sham (P > 0.05). The phytohemagglutinin response was higher in the high TES group 24 h postinjection (P < 0.05) and in the medium TES 48 h postinjection (P < 0.05) as compared with the CHOL group. High dose TES implantation decreased the white blood cell counts as compared with the CHOL and sham groups (P < 0.05). It appears that caponization decreased the blood androgen concentration and enhanced the humoral (anti-NDV and anti-SRBC) immune response. Testosterone implantation up to a threshold concentration could inhibit the humoral (anti-NDV) immune response and increase the cell-mediated (phytohemagglutinin) immune response.

Carbohydrate restriction decreases small LDL particles, attenuates inflammation and alters mechanical properties of aortas in the cholesterol fed guinea pig

Both dietary cholesterol (chol) and carbohydrate restriction (CR) significantly impact plasma lipids, atherogenicity of lipoproteins and inflammatory cytokines. We evaluated the effects of chol and CR on aortic cholesterol and triglycerides accumulation, plasma secretory phospholipase A2 (sPLA2) activity, aorta stiffness as well as aortic cytokine concentration in guinea pigs. Forty adult male guinea pigs (10/group) were fed either low (L) (0.04 g/100g) or high (H) (0.25g/100g) amounts of chol in combination with CR (10% total energy) or high carbohydrates (54% total energy) for 12 wks. Groups fed the high chol (control‐H and CR‐H) had higher cholesterol and triglycerides accumulated in aortas (P&lt; 0.05) and higher sPLA2 activity than those guinea pigs in the L chol groups. CR resulted in lower concentrations of plasma small LDL subfractions (P &lt; 0.01) and aortic cytokines and chemokynes including TNF‐α, IL6 and MPC‐1 (P &lt; 0.01) than the high carbohydrate groups. Regarding the aorta stiffness, the control‐H and the CR‐L were stiffer than the control‐L and the CR‐H groups. These results can be interpreted as different stages of atherosclerosis development. The control‐H diet is postulated to be in the last stage of atherosclerosis, the CR‐H and the control‐L in an intermediate phase and the CR‐L at the beginning of the process. These results demonstrate that CR has a major impact on atherogenicity of lipoproteins, aorta stiffness and aortic cytokine accumulation. In addition, CR diets appeared to ameliorate the atherosclerotic potential of the high cholesterol diets.

Carbohydrate restriction (CR) and dietary cholesterol influence the number of lipoprotein particles and distribution of lipoprotein subfractions in guinea pigs

Guinea pigs (n=10) were randomly assigned to 3 different groups: 42% energy from carbohydrate (CHO) and 0.04% cholesterol (control), 42% CHO and 0.25% cholesterol (HCHO) or 11% energy from CHO and 0.25% cholesterol (CR) for 12 wk. Plasma lipids were evaluated and lipoprotein subclasses and size were analyzed by nuclear magnetic resonance. There were no differences in VLDL, LDL or HDL cholesterol or triglyceride concentrations between the CR and the HCHO groups; however all these plasma lipids were higher compared to the control group (P < 0.0001). High CHOL (HCHO and CR groups) resulted in larger VLDL particles (71.1 ± 6.9, 78.9 ± 3.33 nm, respectively) compared to control (44.3 ± 10.8 nm). In addition, there were higher concentrations of the large VLDL (>60nm) and the medium VLDL (> 27 nm) in the high CHOL groups compared to the control (P < 0.001). Similarly the number of HDL particles and the concentration of the medium (>8.2 nm) and small HDL (>7.2 nm) were higher with the high CHOL (P < 0.001). In contrast, CHO restriction significantly affected the size and concentration of LDL particles. Total LDL particles were lower in the CR (291.3 ± 85.0 nmol/L) compared to HCHO group (467.6 ± 113.1 nmol/L). The concentrations of medium LDL (> 19.8 nm) and small LDL (>18 nm) were lower in the CR group (98.4 ± 90.8 and 29.3 ± 24.9 nmol/L, respectively) than in the HCHO group (261.8 ± 105.8 and 64.9 ± 27.9 nmol/L, respectively) (P < 0.0001). These results indicate that CHOL increased the atherogenicity of both VLDL and HDL while CR decreased the number of LDL particles, specifically the more atherogenic smaller LDL.

Reduction of cardiac functional reserve and elevation of aortic stiffness in hyperlipidemic Yucatan minipigs with systemic and coronary atherosclerosis

To test the hypothesis that cardiac functional reserve is reduced in animals with severe atherosclerosis, Yucatan minipigs were fed a high-cholesterol diet (Chol) for 8 months. Half of them was made diabetic, an additional risk factor for atherosclerosis, with streptozotocin (STZ). Another group of age-matched minipigs were fed a normal diet as controls. At the end of the treatment period, animals were instrumented for the measurement of cardiovascular hemodynamic parameters under isoflurane anesthesia. Cardiac functional reserve was measured by the magnitude of the inotropic response to isoproterenol stress. Hyperlipidemic minipigs developed severe atherosclerotic plaques in the aorta, coronary and iliac artery, accompanied by an increase in the aortic stiffness indexed by increases in pulse wave velocity and augmentation index. These vascular changes were more severe in STZ-induced insulin-dependent diabetes mellitus. The isoproterenol-induced increase in left ventricular contractility (d P/d t) and relaxation (−d P/d t) and, consequently, cardiac output were also significantly reduced in both the Chol groups with or without STZ, compared to control group. Thus, cardiac functional reserve measured by isoproterenol-stimulated responses was reduced in atherosclerotic minipigs, which was further diminished in diabetes.

Fluorescence studies of the self-organization of a cholesterol-bearing polymethacrylate inn-hexane solution

A copolymer of cholesteryl 6-(methacryloyloxy)hexanoate and a small amount of (1-pyrenylmethyl) 6-(methacryloyloxy)hexanoate (Py-C5-MA) was prepared by free radical copolymerization. A copolymer of 1-eicosanylmethacrylate and a small amount of Py-C5-MA was also prepared as a reference copolymer. A wide-angle X-ray diffraction pattern for an n-hexane solution of the cholesterol(Chol)-containing copolymer showed a peak corresponding to a spacing of 5.3 Å. In n-hexane, the hydrodynamic radius (Rh) for the Chol-containing copolymer (Mw = 7.8 × 104) was 8.1 nm, while that of the eicosanyl-containing copolymer (Mw = 4.9 × 104) was 9.6 nm, Rh for the former being smaller than that for the latter, although Mw for the former was higher than that of the latter. 1H-NMR spectra of the Chol-containing polymer in n-hexane-d14 indicated a strong restriction of local motions of pendant Chol groups. Fluorescence spectra of the Chol-containing copolymer in n-hexane indicated that each pyrene group was isolated from others. In n-hexane/benzene mixed solutions of the Chol-containing polymer, the ratio of the intensity of the excimer relative to the monomer emission decreased with increasing the ratio of n-hexane in the mixed solvent. Electron transfer from N,N-dimethylaniline to singlet-excited pyrene chromophores was suppressed in the Chol-containing copolymer in n-hexane. The pyrene chromophores exhibited a long triplet lifetime in n-hexane. These observations led us to conclude that Chol groups formed stacks in n-hexane, and that the pyrene chromophores were trapped in the Chol stacks, leading to the “protection” of pyrene from the bulk phase. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 47–58, 1999

Lovastatin maintains nitric oxide—but not EDHF-mediated endothelium-dependent relaxation in the hypercholesterolemic rabbit carotid artery

The endothelium contributes to the regulation of vascular tone by producing nitric oxide (NO) and the endothelium-derived hyperpolarising factor (EDHF). In hypercholesterolemia, endothelium-dependent relaxation is impaired but can be restored by treatment with lovastatin (LOVAS). We investigated the effects of LOVAS on NO and EDHF-mediated relaxation. Rabbits were fed 1% cholesterol diet for 4 weeks and 0.5% cholesterol for the following 12 weeks (CHOL-group). The LOVAS group additionally received 10 mg of lovastatin over the last 12-week period. Experiments were performed in carotid artery rings. Relaxant responses to acetylcholine (ACh) were recorded in the presence of indomethacin. Nitro- l-arginine (NOARG, 100 μM) and potassium chloride (KCl, 35 mM) were used to differentiate between NO- and EDHF-mediated relaxations. Cholesterol impaired ACh-induced relaxations and this effect was prevented by LOVAS (control 100±1%, CHOL 81±6%, LOVAS 98±1%). In the presence of NOARG, relaxations to ACh were not different between the LOVAS and CHOL groups (control 78±4%, CHOL 64±6%, LOVAS 64±5%). When KCl was used, ACh-induced relaxations were similar in the LOVAS and control group (control 75±5%, CHOL 49±6%, LOVAS 76±2%). In arteries treated with NOARG and KCl together, no relaxations were observed. Relaxations of arteries from the control group were not affected by 18 h preincubation with lovastatin (10μM). Lovastatin selectively maintains nitric oxide-mediated endothelium-dependent relaxation in hypercholesterolemic rabbit carotid arteries.

Photophysical Behavior of Zinc(II) Tetraphenylporphyrin Covalently Incorporated in a Cholesterol-Bearing Polymethacrylate

Photophysical behavior of a zinc(II) tetraphenylporphyrin (ZnTPP) moiety in a copolymer of 0.1 mol % zinc(II) 5-[4-(6-methacryloyloxyhexanoyloxy)phenyl]-10,15,20-triphenylporphynate (ZnTPP-C5-MA) and 99.9 mol % cholesteryl 6-methacryloyloxyhexanate (Chol-C5-MA) was investigated in comparison with that of monomeric ZnTPP-C5-MA. Pendant cholesterol (Chol) groups in the copolymer form stacks in n-hexane (a poor solvent for the copolymer), while no Chol stacks are formed in benzene (a good solvent). The absorption maxima of the Soret and Q bands of monomeric ZnTPP-C5-MA were solvent dependent, i.e. the maxima in n-hexane were 7.6 nm shorter than those in benzene. In contrast, no such solvent dependence was observed for the polymer-bound ZnTPP moiety. Spectral profiles for the fluorescence bands for the polymer-bound ZnTPP moiety and monomeric ZnTPP-C5-MA were very different in n-hexane, i.e. the relative intensity of the 0–0 to 0–1 fluorescence bands for the former was 0.52 while that for the latter was 1.10. The triplet excited lifetime for the polymer-bound Zn-TPP moiety at room temperature was much longer in n-hexane (22 ms) than in benzene (3.7 ms), while the fluorescence lifetime at room temperature was slightly longer in n-hexane (2.52 ns) than in benzene (2.09 ns). The polymer-bound ZnTPP moiety emitted phosphorescence and E-type delayed fluorescence in n-hexane at room temperature, arising from the long triplet lifetime. Fluorescence quenching for the polymer-bound ZnTPP moiety by vitamin-K3 was suppressed in n-hexane, as compared to the quenching of the monomer. All these observations indicate that the ZnTPP chromophores in the copolymer are “protected” in the Chol stacks in n-hexane, leading to an isolation of ZnTPP from the bulk solution phase.

Dietary cholesterol enhances impaired endothelium-dependent relaxations in aortas of salt-induced hypertensive Dahl rats

We investigated the effect of hypercholesterolemia on the vascular reactivity of thoracic aortas isolated from hypertensive Dahl salt-sensitive (DS) rats. DS rats were fed on a low-sodium diet (control group), a low-sodium plus high-cholesterol diet (CHOL group), a high-sodium diet (NaCl group) or a high-sodium plus high-cholesterol diet (NaCl + CHOL group) for 8 weeks. Hypercholesterolemia developed in the CHOL and NaCl + CHOL groups, while hypertension developed in the NaCl and NaCl + CHOL groups, with these changes being greatest in the NaCl + CHOL group. Aortic cholesteryl ester accumulation was observed only in the NaCl + CHOL group. Endothelium-dependent relaxations in response to acetylcholine were significantly attenuated in the aortic rings from the NaCl and NaCl + CHOL groups, compared to the control group. The degree of attenuation in the NaCl + CHOL group was significantly greater than that in the NaCl group. Endothelium-dependent relaxations induced by the calcium ionophore A23187 were attenuated only in the NaCl + CHOL group. Endothelium-independent relaxations in response to sodium nitroprusside were slightly but significantly attenuated in the NaCl + CHOL group. The relaxations in the CHOL group were comparable to those in the control group. These findings indicate that cholesterol feeding strikingly enhances the impaired endothelium-dependent relaxations and the slightly impaired endothelium-independent relaxations in the aorta of DS rats with salt-induced hypertension, parallel to the development of hypertension, hypercholesterolemia and cholesterol deposition.