Transcriptomic therapy for dyslipidemias utilizing nucleic acids targeted at ANGPTL3

2021 ◽  
Author(s):  
Gerald F Watts ◽  
Frederick J Raal ◽  
Dick C Chan
Keyword(s):  
Clinical Trials ◽  
Plasma Lipid ◽  
Lipoprotein Metabolism ◽  
New Approach ◽  
Cholesterol Levels ◽  
Ldl Particles ◽  
Severe Hypertriglyceridemia ◽  
Triglyceride Rich Lipoprotein ◽  
Mixed Hyperlipidemia

Angiopoietin-like protein 3 (ANGPTL3) is a key physiological regulator of plasma lipid and lipoprotein metabolism that involves the control of enzymes, lipoprotein and endothelial lipases. Inhibition of ANGPTL3 offers a new approach for correcting the health risks of dyslipidemia, including familial hypercholesterolemia, mixed hyperlipidemia, metabolic syndrome and/or severe hypertriglyceridemia. ANGPTL3 inhibition with nucleic acid-based antisense oligonucleotide and siRNA can correct dyslipidemia chiefly by reducing production and increasing catabolism of triglyceride-rich lipoprotein and LDL particles. Early clinical trials have demonstrated that these agents can safely and effectively lower plasma triglyceride and LDL-cholesterol levels by up to 70 and 50%, respectively. However, the long-term safety and cost–effectiveness of these agents await to be confirmed in an ongoing and future clinical trials.

scholarly journals Long-term fasting improves lipoprotein-associated atherogenic risk in humans

2021 ◽  
Author(s):  
Franziska Grundler ◽  
Dietmar Plonné ◽  
Robin Mesnage ◽  
Diethard Müller ◽  
Cesare R. Sirtori ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Apolipoprotein A1 ◽  
Health Concern ◽  
Low Density ◽  
Lipoprotein Subclasses ◽  
Ldl Particles ◽  
Increased Risk

Abstract Purpose Dyslipidemia is a major health concern associated with an increased risk of cardiovascular mortality. Long-term fasting (LF) has been shown to improve plasma lipid profile. We performed an in-depth investigation of lipoprotein composition. Methods This observational study included 40 volunteers (50% men, aged 32–65 years), who underwent a medically supervised fast of 14 days (250 kcal/day). Changes in lipid and lipoprotein levels, as well as in lipoprotein subclasses and particles, were measured by ultracentrifugation and nuclear magnetic resonance (NMR) at baseline, and after 7 and 14 fasting days. Results The largest changes were found after 14 fasting days. There were significant reductions in triglycerides (TG, − 0.35 ± 0.1 mmol/L), very low-density lipoprotein (VLDL)-TG (− 0.46 ± 0.08 mmol/L), VLDL-cholesterol (VLDL-C, − 0.16 ± 0.03 mmol/L) and low-density lipoprotein (LDL)-C (− 0.72 ± 0.14 mmol/L). Analysis of LDL subclasses showed a significant decrease in LDL1-C (− 0.16 ± 0.05 mmol/L), LDL2-C (− 0.30 ± 0.06 mmol/L) and LDL3-C (− 0.27 ± 0.05 mmol/L). NMR spectroscopy showed a significant reduction in large VLDL particles (− 5.18 ± 1.26 nmol/L), as well as large (− 244.13 ± 39.45 nmol/L) and small LDL particles (− 38.45 ± 44.04 nmol/L). A significant decrease in high-density lipoprotein (HDL)-C (− 0.16 ± 0.04 mmol/L) was observed. By contrast, the concentration in large HDL particles was significantly raised. Apolipoprotein A1 decreased significantly whereas apolipoprotein B, lipoprotein(a), fibrinogen and high-sensitivity C-reactive protein were unchanged. Conclusion Our results suggest that LF improves lipoprotein levels and lipoprotein subclasses and ameliorates the lipoprotein-associated atherogenic risk profile, suggesting a reduction in the cardiovascular risk linked to dyslipidemia. Trial Registration Study registration number: DRKS-ID: DRKS00010111 Date of registration: 03/06/2016 “retrospectively registered”.

scholarly journals The Description of Lipid Profile on Injectable DMPA Contraception Acceptors in Public Health Center Banjarsengon, Jember District

2021 ◽  
Vol 8 (1) ◽  
pp. 043-048
Author(s):  
Ririn Handayani ◽  
Rizki Fitrianingtyas
Keyword(s):  
Lipid Profile ◽  
Cholesterol Oxidase ◽  
Lipoprotein Metabolism ◽  
The Body ◽  
High Cholesterol ◽  
Exclusion Criteria ◽  
Cholesterol Levels ◽  
Very High ◽  
High Triglyceride

Injectable DMPA contraception can cause changes in lipoprotein metabolism. Changes in fat metabolism occur because of the hormonal influence of progesterone, causing disruption of the balance of lipid profiles in the body. The change in serum lipid profile (trgliseride, total cholesterol, HDL and LDL) in long-term use of DMPA is a risk factor for atherosclerosis and cardiovascular disease. The purpose of this study was to look at the description of the lipid profile at 3 months injection acceptors. The design of the study was descriptive. The population in this study was 76, the number of samples that met the inclusion and exclusion criteria in this study was 30. Examination of the lipid profile was carried out with an enzymatic colorimetric (cholesterol oxidase method / CHOD PAP). The results of lipid profile examination showed that 13.33% had high cholesterol levels, 3.33% had high triglyceride levels, 13.33% had high HDL levels, 20% had high LDL levels and 3.33% have very high LDL levels. The conclusion of this study was long term use of DMPA injection contraception could cause changes in the lipid profile, so it is recommended for acceptors who want to use contraception in the long term to use MKJP as an option so as not to affect the fat profile in the body.

Long-term growth hormone excess induces marked alterations in lipoprotein metabolism in mice

2001 ◽  
Vol 281 (6) ◽  
pp. E1230-E1239 ◽  
Author(s):  
Fredrik Frick ◽  
Mohammad Bohlooly-Y ◽  
Daniel Lindén ◽  
Bob Olsson ◽  
Jan Törnell ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Transgenic Mice ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Male Mice ◽  
Cholesterol Levels ◽  
Transgenic Male ◽  
Gh Excess

The effects of long-term chronic growth hormone (GH) excess on lipid and lipoprotein metabolism were investigated in 8-mo-old bovine GH (bGH)-transgenic mice. Total body weight, serum cholesterol, insulin-like growth factor-I, and insulin levels were higher, whereas serum levels of glucose, free fatty acids, and triglycerides were lower in transgenic mice. Very low-density lipoprotein (VLDL) cholesterol levels were lower, and low-density lipoprotein (LDL) cholesterol levels were higher, in transgenic mice irrespective of gender, whereas only transgenic male mice had higher high-density lipoprotein cholesterol levels. Total serum apolipoprotein B (apoB) levels were not affected, but the amount of apoB in the LDL fraction was higher in transgenic mice. Hepatic LDL receptor expression was unchanged, whereas apoB mRNA editing and hepatic triglyceride secretion rate were reduced in bGH-transgenic male mice. Both lipoprotein lipase activity in adipose and heart tissue and β-adrenergic-stimulated lipolysis were increased in transgenic male mice. The relative weight of adipose tissue was lower in transgenic mice, whereas hepatic triglyceride content was unchanged. Fat feeding of the mice equalized serum triglycerides and free fatty acids in bGH-transgenic and control mice. In summary, long-term GH excess is associated with marked alterations in lipid and lipoprotein metabolism, indicating decreased production and increased degradation of VLDL and preferential flux of fatty acids to muscle tissues.

Reduction of major amputations in the diabetic ischaemic foot: A strategy to "take control" with conservative care as well as revascularisation

VASA ◽  
2001 ◽  
Vol 30 (Supplement 58) ◽  
pp. 6-14 ◽  
Author(s):  
Edmonds ◽  
Foster
Keyword(s):  
Natural History ◽  
Treatment Plan ◽  
Staging System ◽  
Vascular Control ◽  
New Approach ◽  
Conservative Care ◽  
Arterial Bypass ◽  
Therapeutic Footwear ◽  
Frequent Problem

The diabetic ischaemic foot has become an increasingly frequent problem over the last decade. However, we report a new approach consisting of a basic classification, a simple staging system of the natural history and a treatment plan for each stage, within a multi-disciplinary framework. This approach of "taking control" consists of two parts: 1. long-term conservative care including debridement of ulcers (to obtain wound control), eradication of sepsis (micribiological control), and provision of therapeutic footwear (mechanical control), and 2. revascularisation by angioplasty and arterial bypass (vascular control). This approach has led to a 50% reduction in the rate of major amputations in patients attending with ischaemic ulceration and absent foot pulses from 1989 to 1999 (from 4.6% to 2.3% per year). Patients who underwent angioplasty increased from 6% to 13%. Arterial bypass similarly increased from 3% to 7% of cases. However, even with an increased rate of revascularisation, 80% of patients responded to conservative care alone. This,we conclude, is an essential part of the management of all patients with ischaemic feet.

Treatment and secondary prevention of venous thromboembolism in cancer patients

2012 ◽  
Vol 03 (03) ◽  
pp. 121-125
Author(s):  
I. Pabinger ◽  
C. Ay
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Patients With Cancer ◽  
Potential Use

SummaryCancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancerassociated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3-6 months. New oral anticoagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.

Attention To Music In The Years Of Independence: A New Approach To Scientific Research

2020 ◽  
Vol 2 (09) ◽  
pp. 395-398
Author(s):  
Sultanov A. ◽  
Tajiboev E.
Keyword(s):  
Music Education ◽  
Education System ◽  
Scientific Research ◽  
Educational Technologies ◽  
New Approach ◽  
Modern Methods

This article reveals the attention paid to music education in Uzbekistan, the new approach implemented in the education system, the development of pedagogical educational technologies and modern methods based on long-term independence.

CHANGES IN BLOOD PROTEOME OF COSMONAUTS WITH MICRO- AND MACROVASCULAR INJURIES DUE TO G-LOADS AT THE FINAL STAGE OF LONG-DURATION SPACE MISSIONS

2020 ◽  
Vol 54 (5) ◽  
pp. 5-14
Author(s):  
L.Kh. Pastushkova ◽  
◽  
K.S. Kireev ◽  
I.M. Larina ◽  
◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Soft Tissues ◽  
Blood Rheology ◽  
Landing Site ◽  
Space Missions ◽  
Vascular Injuries ◽  
New Approach ◽  
Long Duration ◽  
Integrated Response

The integrated response of the human proteome to re-entry g-loads following long-term space missions was studied in 13 male cosmonauts at the age of 44 ± 6 years. Examination at the landing site discovered local petechial hemorrhages into soft tissues of the back and lower legs. The paper presents a new approach to evaluation of petechia and soft tissue hemorrhages in cosmonauts on return to Earth. Proteomic analysis was performed with the use of LC-MS. Bioinformation analysis was made using Perseus, PubMed, Uniprot and ANDSystem software. Nine out of 19 significantly different (p < 0.05) proteins were related to vascular injuries directly. We described proteins with a primarily protecting effect against endothelial cells apoptosis and augmentation of vascular permeability, proteins that are responsible for blood rheology and proteins antagonistic to the main triggers of ischeamia-reperfusion injuries of the lungs, liver and other parenchymal organs.

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