Effect Of Low-density Lipoprotein Research Articles

Effect of low-density lipoproteins and trehalose on the quality of cryopreserved bovine semen

Background: In artificial insemination, chicken egg yolk is added to bovine semen to protect it during the cryopreservation process, although it contains substances that can affect the microbiological quality and metabolism of sperm. Objective: To evaluate post-thaw quality of bovine cryopreserved semen added with centrifuged and non-centrifuged egg yolk, low-density lipoproteins (LDL), and trehalose (T). Methods: Ten ejaculates from five bulls were cryopreserved under the treatments T1: pure egg yolk (PEY) at 20% v/v, T2: centrifuged egg yolk (CEY) at 20% v/v, T3: LDL at 8% v/v, T4: T at 100 mM, and T5: T at 100 mM plus LDL at 8% v/v (TLDL). Spermatic motility and kinetics, functional membrane integrity (FMI), structural membrane integrity (SMI), sperm vitality (SV) and abnormal morphology (AM) were assessed using the Sperm Class Analyzer (SCA®) system, hypoosmotic test (HOST), SYBR/PI probes, and eosin–nigrosin staining, respectively. A completely randomized design was used. Normal distribution of the variables was validated through the Kolmogórov– Smirnov test. A generalized linear model was used to determine sources of variation. Means were compared using the Tukey test. Results: Inclusion of CEY or LDL had a similar effect on sperm protection, and were superior for motility, kinetics and membrane integrity compared to the other treatments (p<0.05). CEY was superior for progressive motility (p<0.05). The cryoprotective action of LDL was similar to TLDL for motility and kinetics, SMI, SV, and AM (p<0.05). Inclusion of PEY and T resulted in the lowest semen quality (p<0.05). The use of T resulted in a reduction in FMI and SMI (p<0.05). No differences in AM between treatments were found (p>0.05). Conclusions: Egg yolk can be replaced by centrifuged egg yolk or low-density lipoproteins in the freezing extender used for bovine semen used in artificial insemination.

A mendelian randomization study comparing the effect of low-density lipoproteins and triglyceride-rich very low-density lipoproteins on the risk of coronary heart disease

A mendelian randomization study comparing the effect of low-density lipoproteins and triglyceride-rich very low-density lipoproteins on the risk of coronary heart disease

Effect of LDL cholesterol, statins and presence of mutations on the prevalence of type 2 diabetes in heterozygous familial hypercholesterolemia

Patients with heterozygous familial hypercholesterolemia (HeFH) have been reported to be less vulnerable to type 2 diabetes mellitus (T2DM), although the mechanism is unknown. The aims of the present study were to assess the effects of low density lipoprotein (LDL) cholesterol concentration and the presence of FH-causing mutations on T2DM prevalence in HeFH. Data were collected from the Dyslipidemia Registry of the Spanish Arteriosclerosis Society. Inclusion criteria were definite or probable HeFH in patients aged ≥18 years. T2DM prevalence in HeFH patients was compared with data of the general population. 1732 patients were included. The prevalence of T2DM was lower in patients with HeFH compared with the general population (5.94% vs 9.44%; OR: 0.606, 95% CI 0.486–0.755, p < 0.001). Risk factors for developing T2DM were male sex, age, body mass index, hypertension, baseline triglyceride levels and years on statin therapy. The prevalence of T2DM in HeFH patients was 40% lower than that observed in the general population. Gene mutations and LDL cholesterol concentrations were not risk factors associated with the prevalence of T2DM in patients with HeFH. The prevalence of T2DM in patients with HeFH was 40% lower than in the general population matched for age and sex.

Effects of low-density lipoproteins as additive on quality parameters and oxidative stress following cryopreservation of mithun (Bos frontalis) spermatozoa.

Artificial breeding of mithun poses several challenges including lack of standard protocol for cryopreservation of spermatozoa. This is further complicated by harmful effects of hen's egg yolk (EY) as additive in extender. Purified low-density lipoproteins (LDL) extracted from EY have been shown as beneficial over EY extender for long-term semen storage in several species. This investigation explored use of LDL versus EY on semen quality and oxidative stress following freezing-thawing of spermatozoa. A total of 25 of 50 ejaculates based on biophysical parameters were selected for the experiment. After diluting with the Tris-citrate-glycerol (TCG) extender, each sample was split into three equal aliquots: Group I, control, EY; Group II and Group III contained 8% and 10% purified LDL, respectively. Frozen-thawed samples were evaluated for motility parameters (progressive, and in the bovine cervical mucus penetration test [BCMPT]), viability, sperm and nuclear abnormality, acrosome integrity, and enzymatic (leakage of intracellular contents) and biochemical (oxidative stress) profiles and in vitro fertility (IVF) assay. Study revealed a significant (p<.05) improvement in viability, sperm and nuclear abnormality, acrosome integrity, motility (progressive and in cervical mucus), cholesterol content, and reduction in the leakage of intracellular enzymes in Group II. Moreover, intactness of acrosome and biochemical membranes was protected significantly (p<.05) in addition to significant (p<.05) improvement in binding per cent and binding index in IVF assay in extender containing 8% LDL. These results demonstrate that although cryopreservation of mithun's spermatozoa in EY was comparable with other species, addition of 8% LDL holds a clear advantage over EY or 10% LDL.

Effect of low density lipoprotein on replacement of egg yolk in liquid preservation of mithun semen

This investigation explored the use of low density lipoproteins (LDL) from egg yolk (EY) in replacement EY on semen quality parameters (SQPs), velocity and motility parameters by Computer Assisted Sperm Analyzer (CASA) and biochemical parameters following liquid storage (5°C) of mithun semen. A total of 25 ejaculates collected from ten healthy mithun bulls and diluted with the standard tris citrate glycerol (TCG) extender were splited into three equal aliquots: Group 1, Control; EY, Group 2 and Group 3 contained 8 and 10% (w/v on dry weight basis) LDL, respectively. SQPs, CASA and biochemical parameters were evaluated following incubation of semen at 5°C. Results revealed a significant (P&lt;0.05) improvement in these parameters in group 2 as compared to group 1 and 3. It was concluded that addition of 8% LDL (w/v) holds a clear advantage over EY or 10% LDL in preservation of mithun semen at liquid storage.

Effect of Low-Density Lipoproteins on Motility and Path Velocities of Spermatozoa in Sirohi Bucks

A study was conducted to evaluate the effect of low-density lipoproteins (LDL) on motility and path velocities of spermatozoa during freezing and thawing process in Sirohi bucks. Semen (a total of 16 ejaculates) was collected from two adult bucks using artificial vagina. After initial evaluation, semen samples of the two bucks were pooled and divided in two equal parts viz., control and treatment. Control was extended with standard glycerolated tris extender with 3% egg yolk while in treatment, egg yolk was replaced with 8% of LDL extracted from egg yolk. After dilution, the semen samples were subjected to freezing and evaluated for percent live spermatozoa and hypo osmotic swelling test (HOST) after equilibration and thawing and motility pattern (rapid, slow and non-progressive) and path velocities of spermatozoa were evaluated using a CASA. The spermatozoa exhibiting the rapid progression were significantly (P 0.01) < higher in treatment after equilibration. Significantly (P 0.05) higher values of rapid and slow < progressive spermatozoa were observed in treatment compared to control in post-thaw semen. Significantly (P 0.01) higher values for curvilinear velocity (VCL), average path velocity (VAP), < straight line velocity (VSL) and maximum amplitude-lateral head displacement (ALH) were observed in the treatment after equilibration. The result indicated that LDL has a better cryoprotective action resulting in better survival rate and motility after equilibration and thawing compared to egg yolk.

The intervention study of atorvastatin on the effect of proliferation and differentiation and the expression of low density lipoprotein receptor-related protein 5, dickkopf-1 mRNA of osteoblasts caused by low density lipoprotein

Objective The aim of this study was to explore the effect of low density lipoprotein(LDL) on the proliferation and differentiation of MC3T3-E1 osteoblasts, as well as the expression of low density lipoprotein receptor-related protein 5(LRP5) and dickkopf-1(DKK1) mRNA of MC3T3-E1 osteoblasts. The possible mechanisms of the treatment of atorvastatin on LDL expression in MC3T3-E1 osteoblasts were also investigated. Methods Proliferation, osteocalcin expression, LRP5, and expression of DKK1 mRNA of MC3T3-E1 with interaction of LDL at 0.05, 0.10, 0.20 mg/ml levels after 24 h, 48 h, 72 h were detected by CCK8, ELISA, and fluorescence quantitative PCR. Furthermore, proliferation, osteocalcin expression, LRP5 and DKK1 mRNA of MC3T3-E1 after the treatment of atorvastatin of 10-6mol/L and 10-5mol/L were also be studied, respectively. Results The effect of LDL on proliferation, expression of osteocalcin and expression of LRP5 and DKK1 mRNA in MC3T3-E1 osteoblasts was the most obvious under LDL with 0.20 mg/ml level. Under that level, atorvastatin(10-6 mol/L or 10-5 mol/L) was able to make the proliferation of MC3T3-E1 osteoblasts in 48 h and 72 h be decreased, while significantly caused upregulation of osteocalcin, LRP5 mRNA expression; and down regulated DKK1 mRNA expression(all P<0.05). Conclusions Atorvastatin can reduce the inhibitory effect of LDL on the proliferation and differentiation of osteoblasts. The mechanisms of atorvastatin on osteoblasts are possibly related to the osteoblast proliferation and expression of LRP5 mRNA and DKK1 mRNA of osteoblasts of wnt signal pathway. (Chin J Endocrinol Metab, 2015, 31: 707-711) Key words: Low density lipoprotein; Atorvastatin; Osteoblast; Low density lipoprotein receptor-related protein 5; Dickkopf-1

Lipid Levels and Renal Function Decline in Pre-Dialysis Patients

Background: Little is known about the effect of low-density lipoprotein (LDL) cholesterol, triglyceride (TG), and high-density lipoprotein (HDL) cholesterol levels on renal function decline in patients receiving specialized pre-dialysis care. Methods: In the prospective PREPARE-2 study, incident patients starting pre-dialysis care were included when referred to one of the 25 participating Dutch specialized pre-dialysis outpatient clinics (2004-2011). Clinical and laboratory data were collected every 6 months. A linear mixed model was used to compare renal function decline between patients with LDL cholesterol, TG, or HDL cholesterol levels above and below the target goals (LDL cholesterol: <2.50 mmol/l, TG: <2.25 mmol/l, and HDL cholesterol: ≥1.00 mmol/l). Additionally the HDL/LDL cholesterol ratio was investigated (≥0.4). Results: In our study population (n = 306), the median age was 69 years and 70% were male. Patients with LDL cholesterol levels above the target of 2.50 mmol/l experienced an accelerated renal function decline compared to patients with levels below the target (crude additional decline: 0.10 ml/min/1.73 m²/month, 95% CI 0.00-0.20; p < 0.05). A similar trend was found for TG levels above the target of 2.25 mmol/l (0.05 ml/min/1.73 m²/month, 95% CI -0.06 to 0.16) and for a HDL/LDL cholesterol ratio below 0.4 (0.06 ml/min/1.73 m²/month, 95% CI -0.05 to 0.18). Adjustment for potential confounders resulted in similar results, and the exclusion of patients who were prescribed lipid-lowering medication (statin, fibrate, or cholesterol absorption inhibitor) resulted in a slightly larger estimated effect. Conclusion: High levels of LDL cholesterol were associated with an accelerated renal function decline, independent of the prescription of lipid-lowering medication.

Effect of low density lipoprotein (LDL) on stallion sperm motility after cryopreservation

Effect of low density lipoprotein (LDL) on stallion sperm motility after cryopreservation

LDL attenuates VEGF-induced angiogenesis via mechanisms involving VEGFR2 internalization and degradation following endosome-trans-Golgi network trafficking

Considerable efforts have been made to amplify angiogenesis under conditions of hypoxia and ischemia by vascular endothelial growth factor (VEGF) delivery, so far with limited success. Ischemic vascular diseases are often associated with hypercholesterolemia. To elucidate whether the exposure to blood lipids influences VEGF responses of microvessels, we characterized effects of low density lipoprotein (LDL) exposure on the proliferation, migration and tube formation of human umbilical vein endothelial cells. By examining the expression, phosphorylation and downstream signals of VEGF's receptor VEGFR2, we characterized mechanisms controlling angiogenic responses following LDL exposure. LDL attenuated endothelial proliferation, migration and tube formation in a dose-dependent way. Reduced abundance of VEGFR2 and VEGFR1 were noticed in LDL-exposed endothelial cells. In subcellular localization studies that we combined with pharmacological experiments, we showed that the loss of VEGFR2 resulted from its internalization and degradation, the latter of which required syntaxin-16-dependent endosome-trans-Golgi network trafficking. As a consequence, VEGFR2 phosphorylation and downstream signals -specifically Akt and ERK1/2 phosphorylation- were attenuated in response to VEGF treatment. VEGF only partly reversed the effects of LDL on angiogenesis under conditions of normoxia and hypoxia. Our results suggest that angiogenic responses to VEGF are compromised in hypercholesterolemia as a consequence of endosomal VEGFR2 degradation.

The effect of low-density lipoproteins on mesenchymal stromal cells of adipose tissue

The effect of low-density lipoproteins on mesenchymal stromal cells of adipose tissue

Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth

In a screen of drugs previously tested in humans we identified itraconazole, a systemic antifungal, as a potent antagonist of the Hedgehog (Hh) signaling pathway that acts by a mechanism distinct from its inhibitory effect on fungal sterol biosynthesis. Systemically administered itraconazole, like other Hh pathway antagonists, can suppress Hh pathway activity and the growth of medulloblastoma in a mouse allograft model and does so at serum levels comparable to those in patients undergoing antifungal therapy. Mechanistically, itraconazole appears to act on the essential Hh pathway component Smoothened (SMO) by a mechanism distinct from that of cyclopamine and other known SMO antagonists, and prevents the ciliary accumulation of SMO normally caused by Hh stimulation.

Liver X receptor agonist inhibits proliferation of ovarian carcinoma cells stimulated by oxidized low density lipoprotein

Objectives We previously observed an association between ovarian cancer outcome and statin use and hypothesized lipoproteins have direct effects on ovarian cancer proliferation. Here we investigate the direct effects of low density lipoprotein (LDL) and oxidized LDL (oxLDL) on proliferation and the inhibitory effects of fluvastatin and a liver X receptor (LXR) agonist. Methods The effects of LDL, oxLDL, the LXR agonist TO901317, fluvastatin and cisplatin on cellular proliferation were determined using MTT assays. LXR pathway proteins were assayed by immunoblotting. Cytokine expression was determined by antibody array. Results Concentrations of oxLDL as small as 0.1 μg/ml stimulated CAOV3 and SKOV3 proliferation, while LDL had no effect. TO901317 inhibited the proliferation of CAOV3, OVCAR3 and SKOV3 cells stimulated by oxLDL. Fluvastatin inhibited oxLDL mediated proliferation of CAOV3 and SKOV3. Cardiotrophin 1 (CT-1) was mitogenic to CAOV3 and SKOV3, was induced by oxLDL, and was reversed by TO901317. OxLDL increased cisplatin IC50s by 3.8 μM and > 60 μM for CAOV3 and SKOV3 cells, respectively. The LXR pathway proteins CD36, LXR, and ABCA1 were expressed in eight ovarian carcinoma cell lines (A2780, CAOV3, CP70, CSOC882, ES2, OVCAR3, SKOV3). Conclusions OxLDL reduced ovarian carcinoma cell chemosensitivity and stimulated proliferation. These effects were reversed by LXR agonist or fluvastatin. The LXR agonist also inhibited expression of the ovarian cancer mitogen CT-1. These observations suggest a biologic mechanism for our clinical finding that ovarian cancer survival is associated with statin use. Targeting LXR and statin use may have a therapeutic role in ovarian cancer.

Effect of low density lipoprotein on the quality of cryopreserved dog semen

Egg yolk is included in extenders for semen cryopreservation due to its protective effect against cold shock, which is attributed to the presence of low density lipoprotein (LDL). This study evaluates how semen quality is affected by using LDL as a replacement for egg yolk in extenders for cooled and frozen dog semen. In Experiment 1, semen was extended in TRIS–glucose at 5 °C, in four treatments: 20% egg yolk (T1); 6% (T2); 8% (T3); and 10% LDL (T4). Sperm motility and membrane integrity after 24, 48, 72 and 96 h and the 50% conservation rate of motile spermatozoa (50 M) were evaluated. The 50 M was less for T1 than for the other treatments ( P < 0.01), but T2–T4 did not differ ( P > 0.05). In Experiment 2, glycerol at 10% was included in the freezing extender, in treatments similar to those from Experiment 1. Sperm motility and membrane integrity did not differ for T2, T3 and T4 at any period in Experiment 1 and after thawing in Experiment 2 ( P > 0.05), but were greater for all LDL treatments than for T1 ( P < 0.01), in both experiments. Thus, LDL can replace egg yolk in the composition of the TRIS–glucose extender for cooled or frozen dog semen.

LDL adsorbent with dendrimer PAMAM as spacer

Dendritic polymers are three-dimensional, highly ordered compounds formed by reiterative reaction sequences, and via discrete stages referred to as generations. To study the spacer effect of low density lipoprotein (LDL) adsorbent, we linked dendrimer polyamidoamine (PAMAM) generation 1 (G1), generation 3 (G3) and generation 5 (G5) to cellulose beads, respectively, and then determined the adsorption proportion of the adsorbents with PAMAM decorated with taurine. The result shows that the spacer with activated multi-points could efficiently improve the adsorption capacity of the adsorbent.

LDL-mediated interaction of DNA and DNA-anti-DNA immune complexes with cell surface

The effect of low-density lipoprotein (LDL) on the binding of DNA and DNA-anti-DNA immune complexes to cultured human skin fibroblasts was examined. Using radioisotope analysis, ELISA and indirect immunofluorescent staining, a correlation between plasma membrane-bound DNA or DNA-anti-DNA immune complexes and cell-associated LDL was established. It was demonstrated that cytotoxicity and internalization of DNA-anti-DNA immune complexes may be LDL mediated. The data obtained suggest that the binding of the major part of DNA and immune complexes bound to surface of normal skin fibroblasts is due to the formation of a DNA-LDL-LDL receptor linkage. A possible role of LDL-containing immune complexes in the pathogenesis of systemic lupus erythematosus is discussed.

‘Danger’ effect of low-density lipoprotein (LDL) and oxidized LDL on human immature dendritic cells

Dendritic cell (DC) maturation may accelerate autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, and may contribute to accelerated atherosclerosis seen in these patients. The immune system responds to both exogenous and endogenous 'dangerous' signals that can induce dendritic cell maturation. We have found that autologous plasma contains danger signals that induce up-regulation of major histocompatibility complex (MHC) class II and co-stimulatory molecules in immature DCs (iDCs). The objective of this study was to determine whether low-density lipoprotein (LDL) and/or oxidized LDL (oxLDL) constitute danger signals, and to assess the effect of exposure to LDL and oxLDL following monocyte differentiation into iDCs in lipoprotein-deficient serum (LPDS). IDCs were generated in the presence of autologous plasma or LPDS. Expression of maturation and migration molecules was evaluated using flow cytometry, and morphology was assessed by light microscopy. Pro- or anti-apoptotic effect was determined using annexin V and propidium iodide binding. Phagocytosis of apoptotic cells was evaluated using autologous plasma or LPDS. LDL and oxLDL were clearly able to slightly up-regulate levels of HLA-DR and co-stimulatory molecule CD86. High oxLDL concentrations (50-100 microg/ml) were associated with expression of additional maturation molecules. Moreover, iDCs that were prepared in LPDS showed partial maturation following exposure to LDL and oxLDL, and improved tolerogenic apoptotic cell uptake. This study suggests that oxLDL, and to some extent LDL, are at least partly responsible for the iDC 'danger' response induced by autologous plasma.

T-cadherin as a receptor regulating angiogenesis and blood vessel remodeling

The search for a membrane receptor responsible for hormone-like effects of low density lipoproteins (LDL) has revealed two proteins (Mol. wt. 105 and 130 kDa) in the membrane fraction of human aortic smooth muscle cells. These proteins were identified as mature T-cadherin and its unprocessed precursor. T-cadherin was originally cloned from chick embryo brain, where it was implicated in axon guidance in the developing nervous system. Our study on the T-cadherin distribution in human organs and tissues has indicated that T-cadherin is specifically expressed in nervous and cardiovascular system. However, physiological significance of T-cadherin expression in the vasculature, as well as intracellular signaling pathways mediating its effects remain obscure. This review summarizes our current knowledge about intracellular signaling utilized by T-cadherin and discusses possible functions of T-cadherin in the vasculature.

Role for LDL in estradiol-synthesis capacity of bovine ovarian follicles

Abstract The steroidogenic capacity of several tissues has been shown to be regulated by lipoproteins. However, the ability of the various lipoprotein classes to affect steroid production in general and estradiol-synthesis in particular has not been established in bovine ovarian cells. In previous studies, we described alterations in the lipoprotein profiles in follicles of different sizes and corresponding changes in lipoprotein-receptor gene expression. In the present study, the effect of low-density lipoprotein (LDL)-enriched medium on aromatization competence of whole ovarian follicles was determined in vitro. Gene expression of aromatase increased and that of selective-uptake receptors decreased in the presence of LDL. These results suggest a role for LDL availability in folliculogenesis.

Effect of low density lipoprotein on DNA integrity of freezing–thawing boar sperm by neutral comet assay

A modified protocol of neutral comet assay was utilized to assess the effect of low density lipoprotein (LDL) on the DNA integrity of boar freezing–thawing semen. The results demonstrated that the method was high sensitive and easier manipulation and LDL significantly protected sperm DNA integrity ( p < 0.05) from the damage caused by cryopreservation except TD at the concentration of 6%, 7% and TM at 6%, the optimal LDL concentration in diluents was 9%. Moreover, LDL showed better protection in 0.25 ml than in 0.5 ml types of straw ( p < 0.05) and no difference was observed in the same volume straw at the concentration of 9% and 10%. It was just the same for LDL effect on boar sperm DNA in cryopreservation 0 day and 30 days ( p > 0.05).