scholarly journals Atorvastatin Increases the Expression of Long Non-Coding RNAs ARSR and CHROME in Hypercholesterolemic Patients: A Pilot Study

2020 ◽  
Vol 13 (11) ◽  
pp. 382
Author(s):  
Isis Paez ◽  
Yalena Prado ◽  
Carmen G. Ubilla ◽  
Tomás Zambrano ◽  
Luis A. Salazar
Keyword(s):  
Lipid Profile ◽  
Cholesterol Metabolism ◽  
Cholesterol Homeostasis ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Single Nucleotide ◽  
Additional Information ◽  
Before And After ◽  
Non Coding Rnas ◽  
Statin Response

Atorvastatin is extensively used to treat hypercholesterolemia. However, the wide interindividual variability observed in response to this drug still needs further elucidation. Nowadays, the biology of long non-coding RNAs (lncRNAs) is better understood, and some of these molecules have been related to cholesterol metabolism. Therefore, they could provide additional information on variability in response to statins. The objective of this research was to evaluate the effect of atorvastatin on three lncRNAs (lncRNA ARSR: Activated in renal cell carcinoma (RCC) with sunitinib resistance, ENST00000424980; lncRNA LASER: lipid associated single nucleotide polymorphism locus, ENSG00000237937; and lncRNA CHROME: cholesterol homeostasis regulator of miRNA expression, ENSG00000223960) associated with genes involved in cholesterol metabolism as predictors of lipid-lowering therapy performance. Twenty hypercholesterolemic patients were treated for four weeks with atorvastatin (20 mg/day). The lipid profile was determined before and after drug administration using conventional assays. The expression of lncRNAs was assessed in peripheral blood samples by RT-qPCR. As expected, atorvastatin improved the lipid profile, decreasing total cholesterol, LDL-C, and the TC/HDL-C ratio (p < 0.0001) while increasing the expression of lncRNAs ARSR and CHROME (p < 0.0001) upon completion of treatment. LASER did not show significant differences among the groups (p = 0.50). Our results indicate that atorvastatin modulates the expression of cholesterol-related lncRNAs differentially, suggesting that these molecules play a role in the variability of response to this drug; however, additional studies are needed to disclose the implication of this differential regulation on statin response.

scholarly journals PCSK9: BIOLOGICAL ACTIVITY REGULATION AND CONNECTION WITH LIPID AND CARBOHYDRATE METABOLISM

2017 ◽  
Vol 8 (3) ◽  
pp. 70-75
Author(s):  
A O Averkova
Keyword(s):  
Cholesterol Metabolism ◽  
Ldl Receptor ◽  
Current Data ◽  
Cholesterol Homeostasis ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Dietary Regulation ◽  
Lipoprotein Concentration ◽  
Lipoprotein Uptake ◽  
Consequent Increase

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease which plays an important role in the regulation of LDL receptor (LDLR) expression and apolipoprotein B (apoB) lipoprotein cholesterol metabolism. It is well known that hepatic PCSK9 expression, its activity and secretion influence cholesterol homeostasis. An upregulation of PCSK9 causes an increase of LDLR degradation, which results in decrease of apoB lipoprotein uptake, and a consequent increase in plasma lipoprotein concentration, including LDL. Therefore, PCSK9 has become a new target for lipid lowering therapy. The aim of this review is to consider current data on metabolic and dietary regulation of PCSK9 and its effect on cholesterol and apoB lipoproteins metabolism and risk of cardiovascular disease.

scholarly journals The Impact of Anthocyanins and Iridoids on Transcription Factors Crucial for Lipid and Cholesterol Homeostasis

2021 ◽  
Vol 22 (11) ◽  
pp. 6074
Author(s):  
Maciej Danielewski ◽  
Agnieszka Matuszewska ◽  
Adam Szeląg ◽  
Tomasz Sozański
Keyword(s):  
Transcription Factors ◽  
Cholesterol Metabolism ◽  
Binding Protein ◽  
Regulatory Element ◽  
Cholesterol Homeostasis ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cell Functions ◽  
The Impact

Nutrition determines our health, both directly and indirectly. Consumed foods affect the functioning of individual organs as well as entire systems, e.g., the cardiovascular system. There are many different diets, but universal guidelines for proper nutrition are provided in the WHO healthy eating pyramid. According to the latest version, plant products should form the basis of our diet. Many groups of plant compounds with a beneficial effect on human health have been described. Such groups include anthocyanins and iridoids, for which it has been proven that their consumption may lead to, inter alia, antioxidant, cholesterol and lipid-lowering, anti-obesity and anti-diabetic effects. Transcription factors directly affect a number of parameters of cell functions and cellular metabolism. In the context of lipid and cholesterol metabolism, five particularly important transcription factors can be distinguished: liver X receptor (LXR), peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element-binding protein 1c (SREBP-1c). Both anthocyanins and iridoids may alter the expression of these transcription factors. The aim of this review is to collect and systematize knowledge about the impact of anthocyanins and iridoids on transcription factors crucial for lipid and cholesterol homeostasis.

scholarly journals AB0875-HPR NON-PHARMACOLOGICAL AND PHARMACOLOGICAL APPROACHES TO THE MANAGEMENT OF PATIENTS WITH OSTEOARTHRITIS AND LIPID METABOLISM DISORDERS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1461.1-1461
Author(s):  
T. Rogatkina ◽  
O. Korolik ◽  
V. Polyakov ◽  
G. Kravtsov ◽  
Y. Polyakova
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Lipid Metabolism ◽  
Lipid Profile ◽  
Fat Mass ◽  
Prognostic Significance ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lipid Metabolism Disorders ◽  
Group I

Background:Attention is drawn to the frequent combination of osteoarthritis (OA) with cardiovascular disease. Non-specific inflammation plays a significant role in the pathogenesis of OA and atherosclerosis. Limiting the physical activity of patients with OA is an additional important factor aggravating the course of cardiovascular disease (CVD). Chronic pain syndrome, causing a neuroendocrine response, is often the cause of the development of complications of atherosclerotic disease. Dyslipidemia is the main cause of atherosclerosis and vascular thrombosis.Objectives:To study variants of lipid metabolism disorders in female and male patients of different age groups with osteoarthritis.Methods:Case histories of 90 patients with OA were analyzed. The average age of patients was 63.27 ± 11.31 years. The average body mass index (BMI) is 39.8 ± 3.2. All patients underwent questionnaires, general clinical and biochemical blood tests with lipid profile determination, anthropometry, bioimpedansometry, and the main metabolic rate assessment using indirect calorimetry in dynamics (at the beginning of the study and after 3 months).Results:Burdened heredity for obesity, arterial hypertension (AH), diabetes mellitus (DM) was revealed. AH was diagnosed in 76 patients (84.4%), type II diabetes in 17 (18.9%), dyslipidemia and hypercholesterolemia in 56 (62.2%). Statins were taken by 43 patients (47.8%) - group I patients, which is associated with low adherence to therapy, group II included patients who did not initially take statins or stopped taking them at least 6 months before inclusion in the study.Against the background of diet therapy and physiotherapy exercises, BMI (R0.99; p <0.05), fat mass (R0.95; p <0.05) significantly decreased, lipid profile normalization was noted: total cholesterol (R0.66; p <0 .05), LDL (R0.69; p <0.05), HDL (R0.95; p <0.05), TG (R0.57; p <0.05), AST decreased (R0.64; p <0.05) and ALT (R0.76; p <0.05) in both groups of patients, regardless of lipid-lowering therapy. A decrease in fat mass correlated with TG levels (R0.51; p <0.05), an increase in skeletal muscle mass (R0.60; p <0.05), lean mass (R0.72; p <0.05), and active cell mass (R0.59; p <0.05). The lipid profile in the I group of patients was significantly better before and at the end of the study. Long-term effects have not been investigated due to the short duration of the study.Conclusion:In patients with OA, a high frequency of concomitant diseases of the cardiovascular system, lipid metabolism disorders was found. Non-drug therapy has a positive effect on the lipid profile and the level of transaminases. The decrease in body weight due to loss of fat mass reliably correlates with the level of TG. Timely use of statins contributes to the normalization of the lipid profile, reduces the risk of cardiovascular disease in patients with OA. It is necessary to study lipid profile disorders in patients with OA with recommendations for lifestyle modification (diet, physical activity), and if necessary, prescribe lipid-correcting therapy.References:[1]E. Simakova, B. Zavodovsky, L. Sivordova [et al]. Prognostic significance of lipid disorders markers determination in pathogenesis of osteoarthritis. Vestnik Rossijskoj voenno-medicinskoj akademii. 2013. No. 2 (42). P.29-32.[2]Zavodovsky B.V., Sivordova L.E. Prognostic significance value of definition of leptin level determination in osteoarthritis. Siberian Medical Journal (Irkutsk). 2012; 115(8):069-072.Disclosure of Interests:None declared

The Effect of Micronized Fenofibrate on Lipid Profiles of Patients Converted from Gemfibrozil

2002 ◽  
Vol 37 (9) ◽  
pp. 953-956 ◽  
Author(s):  
Jim M. Backes ◽  
Patrick M. Moriarty ◽  
Cheryl A. Gibson
Keyword(s):  
Randomized Trial ◽  
Lipid Profile ◽  
Lipid Profiles ◽  
Comparative Data ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Two Agents ◽  
Lowering Therapy ◽  
Micronized Fenofibrate ◽  
The Mean

Although numerous studies have established the efficacy of micronized fenofibrate (MF) and gemfibrozil in improving lipid profiles, there are limited comparative data on the lipid-lowering effects of these two agents. The objective of this study was to evaluate the mean changes in lipid values of hypertriglyceridemic patients crossed over from gemfibrozil to MF. The Medical charts of 21 patients were analyzed retrospectively. Patients were maintained on gemfibrozil 600 mg twice daily for a minimum of 3 months. The patient's last fasting lipid profile on gemfibrozil was compared to the first lipid profile after crossover to MF 200 to 201 mg/day. Patients were excluded if there were alterations in other lipid-lowering therapy during the cross-over or documented non-adherence. The lipid profiles after the crossover showed a significant reduction in triglycerides (56%; P < 0.05) and TC/HDL ratio (38%; P < 0.05) and a significant increase in HDL (22%; P < 0.05). There were nonsignificant changes in other lipid values: TC (-22%; P = 0.058), LDL (+5%; P = 0.866) and LDL/HDL ratio (+6; P = 1.0). The results show that MF had additional favorable effects on triglycerides, HDL, and TC/HDL ratio compared with gemfibrozil. A larger, randomized trial to confirm these effects is warranted.

scholarly journals Altered Lipid Profile is a Risk Factor for the Progression Andrecurrenceof COVID-19: From Two Retrospective Cohorts

2020 ◽  
Author(s):  
Hui Jin ◽  
Junji He ◽  
Chuan Dong ◽  
Luhong Cao ◽  
Xing Qi ◽  
...  
Keyword(s):  
Risk Factor ◽  
Lipid Profile ◽  
Cox Regression ◽  
Lipid Lowering ◽  
Hospital Death ◽  
Lipid Lowering Therapy ◽  
Clinical Endpoints ◽  
Increased Risk ◽  
The Impact ◽  
The Relationship

Abstract Background The COVID-19 pandemic has spread worldwide. However, the impact of lipid profile and lipid-lowering treatment on clinical endpoints in COVID-19 have not previously been investigated. Methods In this retrospective, multicenter cohort study, we consecutively enrolled 430 adult COVID-19 patients from two Chinese hospitals (one each in Chengdu and Wuhan) admitted during February 2020 and followed-up until April 30. Demographic, metabolic profile, laboratory, treatment and clinical endpoint data including in-hospital death and recurrence of COVID-19, were collected. Results In Chengdu patients, univariable and multivariable Cox regression showed that the low-density lipoprotein cholesterol (LDL-C) dyslipidemia on admission was associated with the recurrence of COVID-19 during the follow-up period. In Wuhan cohort, the patients with triglycerides hyperlipemia had an increased risk of in-hospital death. However, in both cohorts, statin therapy during COVID-19 course did not affect these clinical endpoints. Compared to the Chengdu cohort, the Wuhan patients tended to have more severe COVID-19 but, unexpectedly, had lower levels of serum lipid. It is of interesting to notice that the relationship between the observed biomarkers of inflammation and lipid do not match the relationship between the organ function measures and this lipid. Conclusions The baseline dyslipidemia should be considered as a risk factor for poor prognosis and recurrence of COVID-19. The lipid level may be altered during COVID-19 course, since lipidology may be distinctly affected by both inflammation and organic damage for SARS-CoV-2. Further investigation is needed on the role of use of lipid-lowering therapy among patients with COVID-19 infections.

Abstract 14248: Efficacy and Safety of Bempedoic Acid in Patients Who Cannot Tolerate Statins: Pooled Analysis of 4 Phase 3 Clinical Trials

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ulrich Laufs ◽  
Maciej Banach ◽  
Harold E Bays ◽  
Alberico L Catapano ◽  
P Barton Duell ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Pooled Analysis ◽  
Lipid Lowering ◽  
Drug Discontinuation ◽  
Lipid Lowering Therapy ◽  
Efficacy And Safety ◽  
Statin Intolerance ◽  
Phase 3 ◽  
Additional Information

Introduction: Some patients cannot tolerate statins mainly because of statin-associated muscle symptoms (SAMS). Bempedoic acid (BA) is a prodrug activated in the liver and not in skeletal muscle. BA has been shown to significantly lower LDL-C by a mean of ~18% in patients receiving background maximally tolerated statins and a mean of ~25% in patients with statin intolerance. Objective: Determine efficacy and safety of BA in statin-intolerant patients receiving no background statin therapy across 4 phase 3 clinical trials. Methods: Data were pooled from 4 randomized (2:1), placebo-controlled studies evaluating oral BA 180 mg once daily vs placebo for 12 to 52 weeks. Primary efficacy endpoint was LDL-C % change from baseline to week 12. Safety assessments included treatment-emergent adverse events (TEAEs), adverse events of special interest (AESI), and laboratory values. For patients who reported SAMs, additional information around etiology and location were collected. Results: Of 3621 patients, 586 (394 BA; 192 placebo) reported intolerance to multiple statins because of SAMS or other AEs and received no statins during the studies. Mean baseline LDL-C was 148.7 mg/dL. After 12 weeks, BA significantly lowered LDL-C vs placebo (placebo-corrected, -26.5%; P < 0.001). Myalgia was the top reason for drug discontinuation, but was less common in the BA arm (17.7%) vs placebo (43.5%). CK > 5 х ULN was uncommon in both groups. Among AESIs (Table) , muscle disorders were reported by 12.7% (BA) vs 14.1% (placebo). Myalgia was less common with BA (4.6%) vs placebo (7.3%). Muscle spasms (4.1% vs 3.6%) and pain in extremity (3.3% vs 2.1%) were comparable between treatment groups. Muscular weakness was rare (0.5% BA, 1% placebo). Conclusion: Among the population of patients unable to use statins, BA significantly lowered LDL-C vs placebo without increasing muscle-related TEAEs. BA may be an appropriate lipid-lowering therapy for patients with hyperlipidemia who are statin intolerant.

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