Lipid-Lowering Therapies for Atherosclerosis: Statins, Fibrates, Ezetimibe and PCSK9 monoclonal antibodies

2021 ◽  
Vol 28 ◽  
Author(s):  
Adel Hajj Ali ◽  
Nour Younis ◽  
Rola Abdallah ◽  
Farah Shaer ◽  
Ali Dakroub ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Lipid Metabolism ◽  
Plasma Cholesterol ◽  
Therapeutic Interventions ◽  
Lipid Lowering ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
Peripheral Arterial Diseases ◽  
Branching Points ◽  
Genetic Interventions

: Cardiovascular disease (CVD) remains the primary cause of global morbidity and mortality. CVD includes various life-threatening conditions such as myocardial infarction, stroke and peripheral arterial diseases. In this context, atherosclerosis continues to play the principal role in the pathogenesis of these conditions. Atherosclerosis emanates from a set of modifiable and non-modifiable risk factors that include age, male gender, family history, obesity, smoking, diabetes mellitus and hypertension. Recent evidence classifies atherosclerosis as a latent disease affecting all-sized arteries with a predilection for arterial branching points of decreased or absent blood supply. Atherosclerosis is not only a lipid metabolism disorder, but is also a chronic inflammatory one. In this review, we provide a synoptic discussion of the underlying pathological mechanisms of atherosclerosis along with the currently applied therapeutic interventions. We then discuss the classical lipid-lowering therapies as well as the newly discovered therapies. For the classical therapies, we point out the importance of statins and ezetimibe in reducing plasma cholesterol levels by virtue of their effects on synthesis, reuptake and intestinal absorption of cholesterol. We also discuss the role of fibrates in modulating lipid metabolism and improving the ratio of high-density to low-density density lipoproteins. We then focus on the more recent molecular and genetic interventions exemplified by proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, evinacumab, and microRNA inhibitors. Special attention is also given to clinical trials involving these therapies.

scholarly journals Phenolic Compounds of Propolis Alleviate Lipid Metabolism Disorder

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Lingjie Kong ◽  
Yuhao Zhang ◽  
Zhouxu Feng ◽  
Jie Dong ◽  
Hongcheng Zhang
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Caffeic Acid ◽  
Significant Risk ◽  
Caffeic Acid Phenethyl Ester ◽  
Benzyl Ester ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder

Lipid metabolism disorder is one of the significant risk factors for a multitude of human diseases and has become a serious threat to human health. The present study aimed to evaluate the effects of phenolics from poplar-type propolis on regulating lipid metabolism by using cell models of steatosis induced by palmitic acid (PA). Our study shows that phenolic esters have higher lipid-lowering activities than phenolic acids, especially for three caffeic acid esters, including caffeic acid phenethyl ester (CAPE), caffeic acid cinnamyl ester (CACE), and caffeic acid benzyl ester (CABE). Most notably, CACE presents prominent properties to prevent intracellular lipid accumulation and to amend extracellular adipokine secretion abnormalities. In addition, our results firstly reveal that CACE can alleviate lipid metabolism disorder through mediating protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6) signaling pathway-associated protein expression, suppressing endoplasmic reticulum (ER) stress, and activating peroxisome proliferator-activated receptors (PPARs) by distinct upregulation of PPARα and downregulation of PPARγ.

scholarly journals Use of Network Pharmacology to Investigate the Mechanism by Which Allicin Ameliorates Lipid Metabolism Disorder in HepG2 Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Bijun Cheng ◽  
Tianjiao Li ◽  
Fenglin Li
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Hepg2 Cells ◽  
Experimental Validation ◽  
Biological Activities ◽  
Lipid Lowering ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder

Allicin has been well documented to exhibit a wide spectrum of biological activities, especially lipid-lowering activity, as a promising candidate for the management of nonalcoholic fatty liver disease (NALFD). However, the mechanisms underlying the therapeutic effects of allicin require further investigation. It is tempting to think of combining network pharmacology and experimental validation to investigate the mechanism by which allicin ameliorates lipid metabolism disorder in HepG2 cells. We established a cell model of hepatic steatosis induced by PA to investigate the antisteatotic effects of allicin. The studies showed that allicin reduced PA-induced lipid accumulation using Nile red staining and TC and TG assays. Then, 219 potential targets of allicin were successfully predicted by PharmMapper. According to Reactome Pathway Analysis, 44 potential targets related to lipid metabolism were screened out. Molecular signaling cascades mediated by allicin included PPARA, PPARG, FABP4, and FABP6 by cytoHubba and qPCR analysis. Results revealed that allicin activated the gene expression of PPARA and FABP6 and suppressed the gene expression of FABP4 and PPARG. Thus, the present study united the methods of network pharmacology and experimental validation to investigate the protein targets of allicin on PA-induced lipid metabolism disorders to supply a reference for related application for the first time.

Chlorpyrifos exposure induces lipid metabolism disorder at the physiological and transcriptomic levels in larval zebrafish

2019 ◽  
Vol 51 (9) ◽  
pp. 890-899
Author(s):  
Xiaoyu Wang ◽  
Jiajie Zhou ◽  
Manlu Shen ◽  
Jiayan Shen ◽  
Xinyue Zhang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Acid Synthesis ◽  
Treated Group ◽  
Heart Tissue ◽  
Lipid Metabolism Disorder ◽  
Larval Zebrafish ◽  
Metabolism Disorder ◽  
Glucose And Lipid Metabolism ◽  
Lipid Metabolism Disorders ◽  
Cellular Apoptosis

Abstract Chlorpyrifos (CPF) is a widely used insecticide in pest control, and it can affect aquatic animals by contaminating the water. In this study, larval zebrafish were exposed to CPF at concentrations of 30, 100 and 300 μg/l for 7 days. In the CPF-treated group, lipid droplet accumulation was reduced in larval zebrafish. The levels of triglyceride (TG), total cholesterol (TC), and pyruvate were also decreased after CPF exposure. Cellular apoptosis were significantly increased in the heart tissue after CPF exposure compared with the control. Transcription changes in cardiovascular genes were also observed. Through transcriptome analysis, we found that the transcription of 465 genes changed significantly, with 398 upregulated and 67 downregulated in the CPF-treated group, indicating that CPF exposure altered the transcription of genes. Among these altered genes, a number of genes were closely related to the glucose and lipid metabolism pathways. Furthermore, we also confirmed that the transcription of genes related to fatty acid synthesis, TC synthesis, and lipogenesis were significantly decreased in larval zebrafish after exposure to CPF. These results indicated that CPF exposure induced lipid metabolism disorders associated with cardiovascular toxicity in larval zebrafish.

scholarly journals Quercetin Improves Glucose and Lipid Metabolism of Diabetic Rats: Involvement of Akt Signaling and SIRT1

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jing Peng ◽  
Qingde Li ◽  
Keye Li ◽  
Li Zhu ◽  
Xiaoding Lin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Lipid Metabolism ◽  
Fasting Blood Glucose ◽  
Akt Signaling ◽  
Hepatic Glycogen ◽  
High Dose ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
Glucose And Lipid Metabolism ◽  
Quercetin Treatment

Glucose and lipid metabolism disorder in diabetes mellitus often causes damage to multiple tissues and organs. Diabetes mellitus is beneficially affected by quercetin. However, its concrete mechanisms are yet to be fully elucidated. In our study, diabetes was induced in Sprague-Dawley rats by STZ injection. The rats were randomly divided into normal control, diabetic model, low-dose quercetin treatment, high-dose quercetin treatment, and pioglitazone treatment groups. Fasting blood glucose was collected to evaluate diabetes. Immunohistochemistry and fluorometric assay were performed to explore SIRT1. Akt levels were measured through immunoprecipitation and Western blot. After 12 weeks of quercetin treatment, the biochemical parameters of glucose and lipid metabolism improved to varying degrees. Hepatic histomorphological injury was alleviated, and hepatic glycogen content was increased. The expression and activity of hepatic SIRT1 were enhanced, and Akt was activated by phosphorylation and deacetylation. These results suggested that the beneficial effects of quercetin on glucose and lipid metabolism disorder are probably associated with the upregulated activity and protein level of SIRT1 and its influence on Akt signaling pathway. Hence, quercetin shows potential for the treatment of glucose and lipid metabolism disorder in diabetes mellitus.

scholarly journals 321 HEPATIC HUR PROTECTS AGAINST DIET-INDUCED LIPID METABOLISM DISORDER

2020 ◽  
Vol 158 (6) ◽  
pp. S-1266
Author(s):  
Yanyan Wang ◽  
Pu Ge ◽  
Yunling Tai ◽  
Jilin Wu ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder
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