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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 a novel approach in immunotherapy to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) by targeting lipid metabolism. In addition, CETP vaccines are being explored as a novel strategy for the prevention and treatment of ASCVD by inducing the body to produce antibodies against CETP, which is expected to reduce CETP activity, thereby increasing high-density lipoproteins (HDL) levels. This paper provides a comprehensive overview of the structure of CETP, the mechanisms of lipid transfer and the progress of immunotherapy in the last decade, which provides possible ideas for future development of novel drugs and optimization of immunization strategies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801355 | PMC |
http://dx.doi.org/10.1080/21645515.2025.2462466 | DOI Listing |
Eur Heart J
September 2025
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
Cardiovascular disease remains a major global health challenge, with dyslipidaemia being a key modifiable risk factor. While low density lipoprotein cholesterol (LDL-C) is the primary target for lipid-lowering therapies, recent evidence highlights the importance of triglycerides, apolipoprotein B (apoB), and lipoprotein(a) [Lp(a)] for residual cardiovascular risk. Current lipid-lowering therapies target key enzymes and proteins involved in cholesterol and lipid metabolism.
View Article and Find Full Text PDFMedicine (Baltimore)
August 2025
Department of Otorhinolaryngology, Pengzhou Hospital of Traditional Chinese Medicine, Chengdu, Sichuan, China.
An increasing body of research indicates an association between lipid-lowering medications and sensorineural hearing loss (SNHL), although there is still controversy. Therefore, the aim of this study is to investigate the genetic correlation between different lipid-lowering therapeutic gene targets and SNHL. The genetic association between lipids, lipid-lowering drug target genes, and SNHL was analyzed using a 2-sample Mendelian randomization approach.
View Article and Find Full Text PDFBiochemistry (Mosc)
August 2025
Laboratory of Human Molecular Genetics, National Research Center "Kurchatov Institute", Moscow, 123182, Russia.
The goal of this study was examination of the association between the expression levels of the genes involved in high-density lipoprotein metabolism and atherogenesis and underlying metabolic pathways and the number of stenotic coronary arteries. Expression of 65 preselected genes in the peripheral blood mononuclear cells of the control patients ( = 63) and patients with coronary artery disease (CAD) with one or two (low stenosis group, = 35) or three or four (high stenosis group, = 41) stenotic vessels, confirmed by coronary angiography, was measured with real-time PCR. Functional enrichment analysis was applied for annotation of differentially expressed genes.
View Article and Find Full Text PDFAm J Cardiovasc Drugs
August 2025
Richmond University Medical Center/Mount Sinai, Staten Island, NY, USA.
Despite the well-established benefits of statin therapy in reducing atherosclerotic cardiovascular disease (ASCVD) risk, many patients fail to achieve recommended low-density lipoprotein cholesterol (LDL-C) targets or experience statin intolerance, necessitating alternative approaches. This review examines advances in non-statin lipid-lowering therapies, focusing on proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (monoclonal antibodies and inclisiran), bempedoic acid, and other non-statin lipid medications. We evaluate their mechanisms of action, clinical efficacy, and safety profiles on the basis of landmark trials.
View Article and Find Full Text PDFJ Clin Lipidol
July 2025
Department of Cardiology, Rinku General Medical Center, Osaka, Japan (Dr Yamashita).
Cholesteryl ester transfer protein (CETP) deficiency is a representative molecular abnormality in familial hyperalphalipoproteinemia, a hereditary disorder of lipid metabolism characterized by markedly elevated plasma high-density lipoprotein cholesterol (HDL-C) levels. In this condition, dysfunction of CETP, which mediates the transfer of cholesteryl esters from HDL particles to apolipoprotein (Apo)B-containing lipoproteins, leads to the abnormal accumulation of HDL-C. These HDL particles are unusually large and enriched in cholesteryl esters, ApoCIII, and ApoE, whereas low-density lipoprotein (LDL) particles are small, depleted of cholesteryl esters, and enriched in triglycerides.
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