Cholesteryl ester transfer protein inhibition: a pathway to reducing risk of morbidity and promoting longevity DOI Creative Commons
Michael H. Davidson, Andrew Hsieh, John J.P. Kastelein

et al.

Current Opinion in Lipidology, Journal Year: 2024, Volume and Issue: 35(6), P. 303 - 309

Published: Oct. 17, 2024

Purpose of review To the evidence and describe biological plausibility for benefits inhibiting cholesteryl ester transfer protein (CETP) on multiple organ systems through modification lipoprotein metabolism. Recent findings Results from observational studies, Mendelian randomization analyses, randomized clinical trials support potential CETP inhibition to reduce atherosclerotic cardiovascular disease (ASCVD) risk a reduction apolipoprotein B-containing lipoproteins. In contrast, raising high-density (HDL) particles, as previously hypothesized, did not contribute ASCVD reduction. There is also an expanding body supporting safeguarding against other conditions associated with aging, particularly new-onset type 2 diabetes mellitus dementia, well age-related macular degeneration, septicemia, possibly chronic kidney disease. The latter are likely mediated improved functionality HDL particle, including its role cholesterol efflux antioxidative, anti-inflammatory, antimicrobial activities. Summary At present, there robust reducing activity reduction, exists promotion longevity by risks several conditions. An ongoing large trial program latest potent inhibitor, obicetrapib, expected provide further insight into therapeutic target these various

Language: Английский

Cholesteryl Ester Transfer Protein Inhibitors and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis DOI Creative Commons
Wajeeh Ur Rehman, Merav Yarkoni,

Muhammad Abdullah Ilyas

et al.

Journal of Cardiovascular Development and Disease, Journal Year: 2024, Volume and Issue: 11(5), P. 152 - 152

Published: May 16, 2024

Atherosclerosis is a multi-factorial disease, and low-density lipoprotein cholesterol (LDL-C) critical risk factor in developing atherosclerotic cardiovascular disease (ASCVD). Cholesteryl-ester transfer-protein (CETP), synthesized by the liver, regulates LDL-C high-density (HDL-C) through bidirectional transfer of lipids. The novelty CETP inhibitors (CETPis) has granted new focus towards increasing HDL-C, besides lowering strategies. To date, five CETPis that are projected to improve lipid profiles, torcetrapib, dalcetrapib, evacetrapib, anacetrapib, obicetrapib, have reached late-stage clinical development for ASCVD reduction. Early trials failed reduce occurrences. Given advent some recent large-scale (ACCELERATE, HPS3/TIMI55-REVEAL Collaborative Group), conducting meta-analysis essential investigate CETPis' efficacy.

Language: Английский

Citations

8
Hypercholesterolemia and inflammation—Cooperative cardiovascular risk factors DOI Creative Commons

Antonio Gallo,

Wilfried Le Goff,

Raul D. Santos

et al.

European Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 6, 2024

Abstract Background Maintaining low concentrations of plasma low‐density lipoprotein cholesterol (LDLc) over time decreases the number LDL particles trapped within artery wall, slows progression atherosclerosis and delays age at which mature atherosclerotic plaques develop. This substantially reduces lifetime risk cardiovascular disease (ASCVD) events. In this context, plaque development vulnerability result not only from lipid accumulation but also inflammation. Results Changes in composition immune cells, including macrophages, dendritic T B mast cells neutrophils, along with altered cytokine chemokine release, disrupt equilibrium between inflammation anti‐inflammatory mechanisms sites. Considering that it is a competition LDLc inflammation, instead they are partners crime, present narrative review aims to give an overview main inflammatory molecular pathways linked raised describe impact lipid‐lowering approaches on burden. Although remarkable changes driven by most recent lowering combinations, relative reduction C‐reactive protein appears be independent magnitude lowering. Conclusion Identifying clinical biomarkers (e.g. interleukin‐6) possible targets for therapy holds promise monitoring reducing ASCVD burden suitable patients.

Language: Английский

Citations

7
Exploring emerging pharmacotherapies for type 2 diabetes patients with hypertriglyceridemia DOI
Brian Tomlinson, Paul Chan

Expert Opinion on Pharmacotherapy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 11

Published: Jan. 11, 2025

Introduction Atherogenic dyslipidemia with increased triglycerides, low high-density lipoprotein cholesterol levels and small dense low-density (LDL) particles is a major risk factor contributing to the cardiovascular (CV) in patients type 2 diabetes (T2D). This regarded as residual after achieving target of LDL cholesterol.

Language: Английский

Citations

0
Recent advances in immunotherapy targeting CETP proteins for atherosclerosis prevention DOI Creative Commons
Wenhui Hu, Feng Han,

Ying Liu

et al.

Human Vaccines & Immunotherapeutics, Journal Year: 2025, Volume and Issue: 21(1)

Published: Feb. 5, 2025

Cholesteryl ester transfer protein (CETP) plays a key role in lipoprotein metabolism, and its activity has been linked to the risk of atherosclerosis (AS). CETP inhibitors, such as obicetrapib, represent novel approach immunotherapy reduce atherosclerotic cardiovascular disease (ASCVD) by targeting lipid metabolism. In addition, vaccines are being explored strategy for prevention treatment ASCVD inducing body produce antibodies against CETP, which is expected activity, thereby increasing high-density lipoproteins (HDL) levels. This paper provides comprehensive overview structure mechanisms progress last decade, possible ideas future development drugs optimization immunization strategies.

Language: Английский

Citations

0
Achieving More Optimal Lipid Control with Non-Statin Lipid Lowering Therapy DOI Creative Commons
Stephen J. Nicholls, Adam J. Nelson

Current Atherosclerosis Reports, Journal Year: 2025, Volume and Issue: 27(1)

Published: Feb. 15, 2025

Language: Английский

Citations

0
High-density lipoprotein cholesterol: how studying the ‘good cholesterol’ could improve cardiovascular health DOI Creative Commons

Lucy Diaz,

Ewa Bielczyk-Maczyńska

Open Biology, Journal Year: 2025, Volume and Issue: 15(2)

Published: Feb. 1, 2025

High cholesterol levels are associated with an increased risk of cardiovascular disease, specifically atherosclerosis, a leading cause death worldwide. Atherosclerosis occurs when and fat build up in plaques along blood vessel walls, restricting flow preventing nutrients oxygen from diffusing out the bloodstream. High-density lipoprotein (HDL) particles prevent build-up such plaques, removing excess peripheral tissues delivering it to liver, where can be removed body. This pathway is known as reverse transport (RCT). Because HDL plays key role plaque buildup, understanding how this molecule RCT function body could help us develop much-needed new atherosclerosis therapies prevention strategies. However, metabolism complex, research on has been less favoured than investigating much better-understood molecule, low-density cholesterol, treatment target. More specifically, receptors involved process taking within liver their relationships one another, mechanism whole, or holoparticle uptake remain clarified. In review, we discuss several outstanding mysteries metabolism, consider why previous clinical trials improve health by modulating have unsuccessful argue that essential for crafting interventions reduce disease risk.

Language: Английский

Citations

0
Obicetrapib: There is still Life in the CETP Inhibitor! DOI Open Access
Masatsune Ogura

Journal of Atherosclerosis and Thrombosis, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

1
Obicetrapib exhibits favorable physiochemical and pharmacokinetic properties compared to previous cholesteryl ester transfer protein inhibitors: An integrated summary of results from non‐human primate studies and clinical trials DOI Creative Commons
Stephen J. Nicholls, Adam J. Nelson, John J.P. Kastelein

et al.

Pharmacology Research & Perspectives, Journal Year: 2024, Volume and Issue: 12(6)

Published: Oct. 18, 2024

Abstract Anacetrapib, a cholesteryl ester transfer protein (CETP) inhibitor previously under development, exhibited an usually extended terminal half‐life and large food effect accumulated in adipose tissue. Other CETP inhibitors have not shown such effects. Obicetrapib, potent selective inhibitor, is undergoing Phase III clinical development. Dedicated assessments were conducted pre‐clinical I II studies of obicetrapib to examine the pharmacokinetic issues observed with anacetrapib. After 9 months dosing up 50 mg/kg/day cynomolgus monkeys, was completely eliminated from systemic circulation detected tissue after 13‐week recovery period. In healthy humans receiving 1–25 mg obicetrapib, mean 148, 131, 121 h at 5, 10, 25 mg, respectively, increased plasma levels by ~1.6‐fold 10 dose. At end treatment trials, ranged 194.5 ng/mL 2.5 506.3 mg. Plasma decreased 92.2% 98.5% four 15 weeks post‐treatment, respectively. Obicetrapib shows no clinically relevant accumulation, minimally affected food, has 131 for These data support once daily, chronic trials dyslipidemia management.

Language: Английский

Citations

1
New perspectives on the high-density lipoprotein system and its role in the prevention and treatment of atherosclerotic cardiovascular disease DOI
N. Lan, Gerald F. Watts

Current Opinion in Endocrinology Diabetes and Obesity, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 2, 2024

The causal role of high-density lipoprotein (HDL) in atherosclerotic cardiovascular disease (CVD) remains debated. Considering recent evidence, the purpose this review is to a provide focused update and new perspectives on HDL CVD.

Language: Английский

Citations

0
Evaluating obicetrapib as an emerging treatment for patients with dyslipidemia: a game changer? DOI
Stephen J. Nicholls, Sean Tan,

Julie Butters

et al.

Expert Opinion on Pharmacotherapy, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 26, 2024

Cholesteryl ester transfer protein (CETP) plays an important role in lipid metabolism. Early interest the development of CETP inhibitors proved to be disappointing. Recent has focused on potential for inhibition reduce cardiovascular risk by lowering levels low-density lipoprotein cholesterol (LDL-C).

Language: Английский

Citations

0