Abstract 537: Lipoproteins Transport Functional Non-human Small RNAs that Regulate Gene Networks Spanning Inflammation and Lipid Metabolism

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Ryan M Allen ◽  
Shilin Zhao ◽  
Quanhu Sheng ◽  
MacRae F Linton ◽  
Kasey C Vickers
Keyword(s):  
Lipid Metabolism ◽  
Nucleic Acid ◽  
Gene Networks ◽  
Financial Burden ◽  
Low Density Lipoproteins ◽  
Locked Nucleic Acid ◽  
High Density Lipoproteins ◽  
Low Density ◽  
Mrna Targets ◽  
Regulate Gene

Cardiovascular disease (CVD) is a significant health and financial burden to our society that demands new and more effective therapies. Although dyslipidemias are primary risk factors for CVD, alternative lipoprotein functions also contribute to CVD and warrant greater understanding. We have found that high-density lipoproteins (HDL) transport microRNAs (miRNA) in circulation and HDL-miRNA signatures are significantly altered in hypercholesterolemia and atherosclerosis. Moreover, we found that HDL transfers extracellular miRNAs to recipient cells where they regulate gene expression through post-transcriptional repression of mRNA targets. We used high-throughput small RNA (sRNA) sequencing to identify and quantify miRNAs and novel sRNAs on HDL and other lipoproteins. Most interestingly, we found that the majority of sRNAs on lipoproteins are likely derived from non-human organisms of multiple kingdoms. Based on these observations, we hypothesized that human and non-human sRNAs on lipoproteins are unique regulators of gene networks that contribute to the complex pathophysiology of CVD. To assess this hypothesis, highly pure lipoproteins (HDL, low-density lipoproteins (LDL), and very low-density lipoproteins (VLDL)) were isolated from plasma of hypercholesterolemic (heterozygous familial hypercholesterolemia, n=9) and healthy (n=7) subjects. We found that HDL, LDL, and VLDL each transport unique sRNA signatures, which are differentially altered in hypercholesterolemic subjects. Using a human tissue library, we identified tissues that likely take up non-human sRNAs. We also found that each class of lipoprotein is capable of transferring non-human sRNAs to multiple cell types, and that transfer efficiency is altered in hypercholesterolemia. Lastly, using a combination of in vitro over-expression and locked-nucleic-acid inhibition for candidate, lipoprotein-enriched, non-human sRNAs, we have discovered novel regulatory networks for critical genes in inflammation and lipid metabolism. This work demonstrates that lipoprotein transport of endogenous and exogenous sRNAs likely have complex roles in the progression and resolution of CVD and are a source of untapped potential for nucleic-acid based therapeutics.

scholarly journals Blood cells and their effect on the lipid profile in women with essential hypertension

2020 ◽  
Vol 25 (3) ◽  
pp. 3349
Author(s):  
B. I. Kuznik ◽  
E. S. Guseva ◽  
S. O. Davydov ◽  
Yu. N. Smolyakov ◽  
E. V. Roitman ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Lipid Metabolism ◽  
Antihypertensive Therapy ◽  
Blood Cells ◽  
Low Density Lipoproteins ◽  
Negative Association ◽  
Atherogenic Index ◽  
High Density Lipoproteins ◽  
Low Density ◽  
Healthy Women

Aim. To find out the relationship of particular blood cells (BC) and their ratios with lipid metabolism in patients with essential hypertension (EH), with (EH-1) and without kinesiotherapy (EH-2).Material and methods. The study included 30 healthy women (control group) and 72 women with EH, which were divided into 2 groups: group 1 (EH-1) — 37 women with stage II (target organ damage classification) hypertension who receive antihypertensive therapy; group 2 (EH-2) — 35 women who underwent antihypertensive therapy and kinesiotherapy (3-4 courses for 2-3 years).Results. Correlation analysis revealed that the studied relationships in healthy women, EH-1 and EH-2 women can be either direct or inverse. In healthy women, we observed negative association of monocytes (MON) with atherogenic index (AI), a positive association of basophils (BAS) with high density lipoproteins (HDL) and its negative association with low density lipoproteins (LDL), very low density lipoproteins (VLDL) and AI and red blood cells/platelets (RBC/PLT ratio) with HDL. Negative associations of lymphocytes (LYM)/BAS ratio with triglyceride (TG) and eosinophils (EOS)/BAS ratio with LDL were also detected. Patients with EH-1 had a direct relationship between LYM/EOS ratio and TG. In patients with EH-2, a negative relationship was found between PLT and HDL, MON and HDL, neutrophils (NEU)/MON ratio and TAG, and a positive — between white blood cells (WBC), NEU, MON and AI, LYM and TAG, MON and TAG, as well as AI.Conclusion. The obtained data indicate that all BC and their ratios in women with/without EH and with/without kinesiotherapy affect the lipid metabolism.

scholarly journals Changes in lipid metabolism in the pre- and postoperative periods in obese patients with laparoscopic cholecystectomy

2021 ◽  
Vol 17 (1) ◽  
pp. 55-58
Author(s):  
A.O. Maisuradze ◽  
I.V. Chubuk
Keyword(s):  
Laparoscopic Cholecystectomy ◽  
Lipid Metabolism ◽  
Total Cholesterol ◽  
Low Density Lipoproteins ◽  
The Body ◽  
High Density Lipoproteins ◽  
Low Density ◽  
Obese Patients ◽  
Obese People ◽  
Group 1

Background. Changes in lipid metabolism indicators in the pre- and postoperative periods are due to frequent metabolic disorders in obese people and particular difficulties with the selection of appropriate therapy. In turn, the cause for metabolic changes in the body is the influence of a certain extreme situation — surgical intervention. Objective: to study the changes in lipid metabolism in the pre- and postoperative periods in obese patients with laparoscopic cholecystectomy. Materials and methods. The study involved 50 individuals (mean age — 47.0 ± 1.5 years), who underwent surgery for acute cholecystitis by laparoscopic cholecystectomy. The patients were divided into 2 groups: 1 — obese, 2 — non-obese. The level of triglycerides, total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL) was assessed in all patients and compared in the preoperative period and on days 1 and 5 after surgery. Results. The parameters of lipid metabolism in the pre- and postoperative periods in all groups had permissible fluctuations, given the fact that in obese patients lipids were initially increased compared to patients without obesity. In the postoperative period in group 1 on the first day, there was a decrease in triglycerides (1.1 ± 0.6 mmol/L) from the baseline, in total cholesterol (4.5 ± 0.3 mmol/L), an increase in HDL cholesterol (1.5 ± 0.2 mmol/L), a decrease in LDL (2.9 ± 0.2 mmol/L) and VLDL (1.0 ± 0.2 mmol/L). In group 2, indicators of triglyceri­des (0.6 ± 0.2 mmol/L), total cholesterol (3.4 ± 0.1 mmol/L), LDL (1.9 ± 0.3 mmol/L) and VLDL (0.8 ± 0.2 mmol/L) also tended to decrease and there was an increase in HDL (1.6 ± 0.1 mmol/L), but these values, regardless of their variation, were within the normal range. In group 1, three patients showed cognitive impairment, which was due to a significant increase in LDL over HDL and the possible development of atherosclerosis, which could lead to cerebrovascular accident. Conclusions. After conducting a study between two groups in which the lipids were studied, a variation in parame­ters was revealed in both groups, which is due to the characteristics of metabolism in such patients and the influence of surgical stress. Based on this, control and regulation of lipid values should be carried out in all patients with dyslipidemia, and in obese patients, additional consideration should be given to risk factors, concomitant diseases and possible complications.

scholarly journals THE PECULARITIES OF CORRELATION BETWEEN INSULIN RESISTANCE, CARBOHYDRATE AND LIPID METABOLISM INDICES IN PATIENTS WITH GRAVES’DISEASE

2017 ◽  
Vol 1 ◽  
pp. 3-9
Author(s):  
Orysia Lishchuk ◽  
Olesya Kikhtyak ◽  
Khrystyna Moskva
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Thyroid Stimulating Hormone ◽  
Low Density Lipoproteins ◽  
High Density ◽  
Free Thyroxine ◽  
High Density Lipoproteins ◽  
Graves Disease ◽  
Low Density ◽  
Stimulating Hormone

Aim. The number of patients with endocrine disorders in the world, in particular, Graves’ disease is continuously increasing. Recent studies have determined the fact of insulin resistance in thyroid disorders. On the one hand, numerous researches prove correlation of hypothyroidism with arterial hypertension, ischaemic heart disease and lipid metabolism disorder, on the other – carbohydrate metabolism disorder and hyper-sympathicotonia are closely associated with hyperthyroidism. The subject of the research was to study the correlation of insulin resistance, lipid and carbohydrate metabolism indices in patients with Graves’disease. Material and Methods. During the study 53 (37 female and 16 male) patients with Graves’ disease with noticed IR have been examined. At the beginning, after 3– and 6-months thyreostatic therapy with insulin sensitizers (metformin or pioglitazone) the following investigations have been performed: assessing thyroid-stimulating hormone levels, free thyroxine and triiodothyronine; assessing glycated haemoglobin, glucose, C-peptide and fasting insulin as primary IR markers; calculating НОМА-IR index for analysing tissue sensitivity to insulin; calculating НОМА-β index for evaluating the functional capacity of β-cells of islets of Langerhans; measuring Caro indices to monitor hyperinsulinemia, measuring total cholesterol level, low-density lipoproteins, very-low-density lipoproteins, high-density lipoproteins , triglycerides, for analysing IR in relation to lipid metabolism. Results. The research results found out that free thyroid hormones and thyroid-stimulating hormone are closely related to lipid metabolism. Thus, thyroid-stimulating hormone was characterized as having direct correlation with low-density lipoproteins, while the free thyroxine inversely correlated with total cholesterol, low-density lipoproteins, and high-density lipoproteins. The free triiodothyronine negatively correlated with high-density lipoproteins. The research has also determined the direct correlation between insulin and free thyroxine, as well as free triiodothyronine in patients with diffuse toxic goitre. Conclusions. The study proves the presence of insulin resistance in patients with Graves’ disease that generates interest to further study of the changes in insulin sensitivity, relation of insulin resistance to thyroid-stimulating hormone, thyroid hormones and looking for the ways to correct these disorders.

scholarly journals Parametry metabolizma i gemostazapri endogennom giperkortitsizme s narusheniemuglevodnogo obmena

2011 ◽  
Vol 8 (3) ◽  
pp. 26-29
Author(s):  
G G Petrik ◽  
S A Pavlishchuk
Keyword(s):  
Diabetes Mellitus ◽  
Lipid Metabolism ◽  
Adrenal Gland ◽  
Low Density Lipoproteins ◽  
High Density Lipoproteins ◽  
Control Group ◽  
Low Density ◽  
Average Volume ◽  
Chronic Hyperglycemia ◽  
The Impact

The aim of the study was to determine peculiarities of protein and lipid metabolism as well as platelet-coagulation hemostasis depending on the pathogenesis of the endogenous hypercortisolism and assessment of the impact of chronic hyperglycemia on studied parameters. Materials and methods. The study included 19 patients with pituitary microadenomas with median age of 45,0 (41; 49) years and 9 patients with nodular adrenal gland hyperplasia aged 49,5 (42; 57) years, 14 of whom had diabetes mellitus. Results. Biochemical and coagulation parameters in patients with endogenous hyperpercortisolism regardless of ethiology Cushing`s syndrome differed from the control group in increased concentration of total cholesterol, high-density lipoproteins, low-density lipoproteins, alpha2-globulins and decreased gamma globulins, as well as in increased average volume of platelets and enhanced aggregation properties. Carbohydrate metabolism disorders were not characterized by significant differences in metabolic parameters and platelet hemostasis, but were accompanied by the reduction of APTT.

Tumor necrosis factor-alpha inhibits lipid and lipoprotein transport by Caco-2 cells

1995 ◽  
Vol 269 (6) ◽  
pp. G953-G960 ◽  
Author(s):  
M. Mehran ◽  
E. Seidman ◽  
R. Marchand ◽  
C. Gurbindo ◽  
E. Levy
Keyword(s):  
Lipid Metabolism ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Low Density Lipoproteins ◽  
Tnf Alpha ◽  
Low Density ◽  
Necrosis Factor Alpha ◽  
Apo B ◽  
Factor Alpha ◽  
Necrosis Factor

Cytokines, important mediators of inflammation, have been shown to cause disturbances in circulating and hepatic lipid metabolism. Although the intestine plays a major role in dietary fat transport and largely contributes to plasma lipoproteins, the effects of cytokines on intestinal lipid handling remain unknown. In the present study, the modulation of lipid, apoprotein, and lipoprotein synthesis and secretion by tumor necrosis factor-alpha (TNF-alpha) was investigated in Caco-2 cells. Highly differentiated and polarized cells (20 days in culture) were incubated for 20 h with recombinant human TNF-alpha (100-500 ng/ml). No cytotoxic effect of TNF-alpha cells was observed, as indicated by the determinations of Caco-2 cell viability and monolayer transepithelial resistance. Moreover, no differences in cell maturation (sucrase activity) or cell proliferation ([3H]thymidine incorporation and cell cycle analysis) were detected between treated and control cultures. Significant inhibition of lipid secretion by TNF-alpha was observed, with the greatest reduction at 500 ng/ml. TNF-alpha significantly decreased Caco-2 cell secretion of phospholipids (22%), triglycerides (30%), and cholesteryl ester (37%). It also significantly diminished the export of newly synthesized low-density lipoproteins (LDL; 20%) and high-density lipoproteins (HDL; 13%), with a lesser effect on very low-density lipoproteins (VLDL; 3%). The lipid composition of these lipoproteins was minimally affected. De novo synthesis of apo A-I, apo B-100, and apo B-48 was also markedly reduced by TNF-alpha. Sphingomyelinase activity was not increased and cell content of sphingomyelin was not altered, suggesting that inhibitory effects on lipid and apoprotein of TNF-alpha were not mediated by the ceramide pathway. Our results indicate that TNF-alpha may play a role in modulating intestinal lipid metabolism, thus affecting circulating lipoproteins.

Selective uptake of cholesteryl esters from various classes of lipoproteins by HepG2 cells

1999 ◽  
Vol 77 (2) ◽  
pp. 157-163 ◽  
Author(s):  
Louise Brissette ◽  
Marie-Claude Charest ◽  
Louise Falstrault ◽  
Julie Lafond ◽  
David Rhainds ◽  
...  
Keyword(s):  
Total Lipid ◽  
Hepg2 Cells ◽  
Ldl Receptor ◽  
Inverse Correlation ◽  
Low Density Lipoproteins ◽  
High Density Lipoproteins ◽  
Low Density ◽  
Cholesteryl Esters ◽  
Very Low Density Lipoproteins ◽  
Selective Uptake

Selective uptake of cholesteryl esters (CE) from lipoproteins by cells has been extensively studied with high density lipoproteins (HDL). It is only recently that such a mechanism has been attributed to intermediate and low density lipoproteins (IDL and LDL). Here, we compare the association of proteins and CE from very low density lipoproteins (VLDL), IDL, LDL and HDL3 to HepG2 cells. These lipoproteins were either labelled in proteins with 125I or in CE with 3H-cholesteryl oleate. We show that, at any lipoprotein concentration, protein association to the cells is significantly smaller for IDL, LDL, and HDL3 than CE association, but not for VLDL. At a concentration of 20 µg lipoprotein/mL, these associations reveal CE-selective uptake in the order of 2-, 4-, and 11-fold for IDL, LDL, and HDL3, respectively. These studies reveal that LDL and HDL3 are good selective donors of CE to HepG2 cells, while IDL is a poor donor and VLDL is not a donor. A significant inverse correlation (r2 = 0.973) was found between the total lipid/protein ratios of the four classes of lipoproteins and the extent of CE-selective uptake by HepG2 cells. The fate of 3H-CE of the two best CE donors (LDL and HDL3) was followed in HepG2 cells after 3 h of incubation. Cells were shown to hydrolyze approximately 25% of the 3H-CE of both lipoproteins. However, when the cells were treated with 100 µM of chloroquine, a lysosomotropic agent, 85 and 40% of 3H-CE hydrolysis was lost for LDL and HDL3, respectively. The fate of LDL and HDL3-CE in HepG2 cells deficient in LDL-receptor was found to be the same, indicating that the portion of CE hydrolysis sensitive to chloroquine is not significantly linked to LDL-receptor activity. Thus, in HepG2 cells, the magnitude of CE-selective uptake is inversely correlated with the total lipid/protein ratios of the lipoproteins and CE-selective uptake from the two best CE donors (LDL and HDL3) appears to follow different pathways.Key words: lipoprotein, receptor, HepG2 cell, selective uptake, lipid, cholesterol, binding.

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