Triglyceride-Rich Lipoprotein Metabolism: Key Regulators of Their Flux

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(13), P. 4399 - 4399

Published: June 29, 2023

The residual risk for arteriosclerotic cardiovascular disease after optimal statin treatment may amount to 50% and is the consequence of both immunological lipid disturbances. Regarding disturbances, role triglyceride-rich lipoproteins (TRLs) their remnants has come forefront in past decade. Triglycerides (TGs) stand as markers catabolism TRLs that tend contain twice much cholesterol compared LDL. accumulation circulating partially lipolyzed derivatives, known “remnants”, caused mainly by ineffective triglyceride catabolism. These cholesterol-enriched remnant particles are hypothesized contribute atherogenesis. aim present narrative review briefly summarize main pathways TRL metabolism, bringing newly discovered apolipoproteins, key physiological function lipoprotein lipase its regulators, importance fluxes these post-prandial period, catabolic rates apo CIII angiopoietin-like proteins partition during fast-fed cycle. Finally, we provide a succinct summary new old therapeutic armamentarium outcomes current trials with final outlook on different methodological approaches measuring remnants, still search gold standard.

Language: Английский

---

The role of adherence in patients with chronic diseases

European Journal of Internal Medicine, Journal Year: 2023, Volume and Issue: 119, P. 1 - 5

Published: July 20, 2023

In the long-term management of chronic diseases, adherence and persistence to prescribed medications are continuous challenges in order obtain all potential benefits drug therapies. Suboptimal discontinuations therapies remain most frequent reasons why several diseases poorly controlled population. One main issue is that physicians relatively limited time tools detect patients with a poor adherence. The present review discusses future strategies now available or being developed support provides some simple clues identify at high risk discontinuation clinic.

Language: Английский

---

​Comprehensive mendelian randomization analysis of plasma proteomics to identify new therapeutic targets for the treatment of coronary heart disease and myocardial infarction

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 30, 2024

Ischemic heart disease is one of the leading causes mortality worldwide, and thus calls for development more effective therapeutic strategies. This study aimed to identify potential targets coronary (CHD) myocardial infarction (MI) by investigating causal relationship between plasma proteins these conditions.

Language: Английский

---

Lipoprotein Lipase: Is It a Magic Target for the Treatment of Hypertriglyceridemia

Endocrinology and Metabolism, Journal Year: 2022, Volume and Issue: 37(4), P. 575 - 586

Published: Aug. 29, 2022

High levels of triglycerides (TG) and triglyceride-rich lipoproteins (TGRLs) confer a residual risk cardiovascular disease after optimal low-density lipoprotein cholesterol (LDL-C)-lowering therapy. Consensus has been made that LDL-C is non-arguable primary target for lipid lowering treatment, but the optimization TGRL reducing remnant diseases urged. Omega-3 fatty acids fibrates are used to reduce TG levels, many patients still have high combined with low high-density concentration need be ideally treated. Lipoprotein lipase (LPL) key regulator TGs hydrolyzes glycerol free in particles storage consumption peripheral organs. A deeper understanding human genetics enabled identification proteins regulating LPL activity, which include apolipoproteins angiopoietin-like families. Novel therapeutic approach such as antisense oligonucleotides monoclonal antibodies regulate developed recent decades. In this article, we focus on biology its modulators review clinical application, including genetic studies trials novel therapeutics. Optimization activity lower could eventually incident atherosclerotic conjunction successful reduction.

Language: Английский

---

Evolving Management of Low‐Density Lipoprotein Cholesterol: A Personalized Approach to Preventing Atherosclerotic Cardiovascular Disease Across the Risk Continuum

Journal of the American Heart Association, Journal Year: 2023, Volume and Issue: 12(11)

Published: June 1, 2023

Management of elevated low‐density lipoprotein cholesterol (LDL‐C) is central to preventing atherosclerotic cardiovascular disease (ASCVD) and key reducing the risk ASCVD events. Current guidelines on management blood recommend statins as first‐line therapy for LDL‐C reduction according an individual's baseline levels. The addition nonstatin lipid‐lowering achieve intensive lowering recommended patients at very high events, including with familial hypercholesterolemia who have not achieved adequate alone. Despite guideline recommendations clinical trial evidence support use therapies reduction, most or do meet thresholds. This review explores challenges associated in contemporary practice proposes a framework rethinking binary definition ASCVD, shifting from “primary” versus “secondary” prevention “continuum risk.” approach considers role plaque burden progression subclinical emphasizes importance early assessment treatment first Patients events require significant should be considered combination comprising statin agents. Practical guidance pharmacological LDL‐C, both now future, provided.

Language: Английский

---

Advances in Treatment of Dyslipidemia

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13288 - 13288

Published: Aug. 27, 2023

Dyslipidemias have emerged as prevalent disorders among patients, posing significant risks for the development and progression of cardiovascular diseases. These conditions are characterized by elevated levels total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL-C). This review delves into current treatment approach, focusing on equalizing these parameters while enhancing overall quality life patients. Through an extensive analysis clinical trials, we identify that necessitate alternative strategies, notably familial hypercholesterolemia. The primary objective this is to consolidate existing information concerning drugs with potential revolutionize dyslipidemia management significantly. Among promising pharmaceuticals, highlight alirocumab, bempedoic acid, antisense oligonucleotides, angiopoietin-like protein inhibitors, apolipoprotein C-III (APOC3) lomitapide, ester transfer (CETP) inhibitors. Our demonstrates pivotal roles played each in targeting specific lipid metabolism. We outline future landscape treatment, envisaging a more tailored effective therapeutic approach address widespread medical concern.

Language: Английский

---

The cell origins of foam cell and lipid metabolism regulated by mechanical stress in atherosclerosis

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: April 13, 2023

Atherosclerosis is an inflammatory disease initiated by endothelial activation, in which lipoprotein, cholesterol, extracellular matrix, and various types of immune non-immune cells are accumulated formed into plaques on the arterial wall suffering from disturbed flow, characterized low oscillating shear stress. Foam a major cellular component atherosclerotic plaques, play indispensable role occurrence, development rupture plaques. It was previously believed that foam were derived macrophages or smooth muscle cells, but recent studies have suggested there other sources cells. Many found distribution not random distributed at bend bifurcation tree. The plaque affected mechanical In this review, we reviewed advances cell formation atherosclerosis regulation lipid metabolism forces. These findings provide new clues for investigating mechanisms progression.

Language: Английский

---

Lipid Variability Induces Endothelial Dysfunction by Increasing Inflammation and Oxidative Stress

Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 39(3), P. 511 - 520

Published: May 16, 2024

Background: This study investigates the impact of fluctuating lipid levels on endothelial dysfunction.Methods: Human aortic and umbilical vein cells were cultured under varying palmitic acid (PA) concentrations: 0, 50, 100 μM, in a variability group alternating between 0 μM PA every 8 hours for 48 hours. In group, exposed to during final before analysis. We assessed inflammation using real-time polymerase chain reaction, Western blot, cytokine enzyme-linked immunosorbent assay (ELISA); reactive oxygen species (ROS) with dichlorofluorescin diacetate assay; mitochondrial function through consumption rates via XF24 flux analyzer; cell functionality wound healing adhesion assays. Cell viability was evaluated MTT assay.Results: Variable significantly upregulated inflammatory genes molecules (Il6, Mcp1, Icam, Vcam, E-selectin, iNos) at both transcriptomic protein human cells. Oscillating reduced basal respiration, adenosine triphosphate synthesis, maximal indicating dysfunction. also elevated ROS levels, contributing chronic state. Functionally, these changes impaired migration increased monocyte adhesion, induced apoptosis, evidenced by viability, BAX, decreased BCL2 expression.Conclusion: Lipid induce dysfunction elevating oxidative stress, providing mechanistic insights into how increases cardiovascular risk.

Language: Английский

---

Modulating effects of crocin on lipids and lipoproteins: Mechanisms and potential benefits

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e28837 - e28837

Published: April 1, 2024

Dyslipidemia poses a significant risk to cardiovascular health in both diabetic and non-diabetic individuals. Therefore, it is crucial normalize lipid homeostasis order prevent or minimize complications associated with dyslipidemia. However, pharmacological interventions for controlling metabolism often come adverse effects. As an alternative, utilizing herbal-based agents, which typically have fewer side effects, holds promise. Crocin, naturally occurring nutraceutical, has been shown impact various intracellular pathways, reduce oxidative stress, alleviate inflammatory processes. Recent evidence suggests that crocin may also confer lipid-related benefits potentially contribute the normalization of homeostasis. specific advantages cellular pathways involved are not yet well understood. In this review, we present latest findings regarding crocin, could be instrumental preventing reducing disorders Additionally, explore potential mechanisms mediate these benefits.

Language: Английский

---

CXCL9, IL2RB, and SPP1, potential diagnostic biomarkers in the co-morbidity pattern of atherosclerosis and non-alcoholic steatohepatitis

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 16, 2024

Abstract Non-alcoholic steatohepatitis (NASH) is a hepatocyte inflammation based on hepatocellular steatosis, yet there no effective drug treatment. Atherosclerosis (AS) caused by lipid deposition in the endothelium, which can lead to various cardiovascular diseases. NASH and AS share common risk factors, also elevate of AS, causing higher morbidity mortality rate for atherosclerotic heart disease. Therefore, timely detection diagnosis are particularly important. In this study, differential gene expression analysis weighted co-expression network were performed (GSE100927) (GSE89632) datasets obtain crosstalk genes, respectively. Then, candidate Hub genes screened using four topological algorithms externally validated GSE43292 GSE63067 genes. Furthermore, immune infiltration set variation explore underlying mechanisms. The DGIbd database was used screen drugs NASH. Finally, model constructed free fatty acid-induced human L02 cells, an lipopolysaccharide-induced HUVECs, co-morbidity cells HUVECs verify expression. result showed that total 113 both identified as enrichment indicated these mainly involved regulation metabolism-related pathways. 28 according algorithms, CXCL9, IL2RB, SPP1 after vitro experiments external dataset validation. ROC curves SVM modeling demonstrated good diagnostic efficacy three addition, strongly associated with cell infiltration, especially macrophages γ–δ T infiltration. five potential therapeutic identified. has-miR-185 hsa-miR-335 closely related This study demonstrates may serve biomarkers patterns targets therapy.

Language: Английский

---