The failure of the cholesterol ester transfer protein (CETP) inhibitor, torcetrapib, has led to questions regarding whether the molecule itself or the mechanism of CETP inhibition was responsible for the adverse cardiovascular outcomes. Given the association with increases in blood pressure and plasma aldosterone levels, torcetrapib has been postulated to have adverse 'off-target' effects. In this issue of British Journal of Pharmacology, Forrest and co-workers have elegantly investigated these effects, demonstrating two salient points -- (1) the pressor effect of torcetrapib is independent of CETP inhibition and (2) although associated with hyperaldosteronism, the pressor effect is likely not mediated by hyperaldosteronism. Anacetrapib, by contrast, did not demonstrate any pressor or off-target effects. Despite these findings, it remains to be proven whether the adverse cardiovascular outcomes from torcetrapib were indeed related to the pressor effects and whether CETP inhibition by other agents will result in beneficial clinical outcomes. Yet, the studies of Forrest and co-workers do bring us closer to unravelling the reasons behind the failure of torcetrapib.
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http://dx.doi.org/10.1038/bjp.2008.248 | DOI Listing |
Heliyon
January 2025
Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, China.
Objective: Observational studies suggest that blood lipids are a risk factor for uterine fibroids (UFs) and that lipid-lowering drugs are beneficial for the treatment and prevention of UF; however, the conclusions are inconsistent. We aimed to determine the causal effects of lipids and lipid-lowering drugs on UFs using Mendelian randomization (MR).
Methods: Genetic variants from genome-wide association studies (GWAS) of lipid traits and variants in genes encoding lipid-lowering drug targets were extracted, and two independent UF GWAS were set as the outcome.
Expert Opin Pharmacother
December 2024
Department of Metabolic Medicine/Chemical Pathology Guy's, St Thomas' Hospitals, London, UK.
Introduction: Lipid-lowering therapies are well established for the treatment of cardiovascular disease (CVD). Historically monotherapy studies have been performed, but the introduction of statins has led to these drugs being recognized as baseline therapies and to the investigation of combination therapy of both older and newer medications with them.
Areas Covered: Surrogate marker studies have shown additive effects on LDL-C, triglycerides and HDL-C of combination therapies with statins and these have extended to lipoprotein (a).
Alzheimers Res Ther
December 2024
Division of Psychiatry, University College London, 149 Tottenham Court Road, W1T 7NF, London, UK.
A recent paper concluded that cholesteryl ester transfer protein (CETP) inhibition may be a viable target to treat dementia, based on human genetic evidence of a protective effect of target inhibition on risk of Lewy body and Parkinson's dementia. Alzheimer's disease, which is by far the most prevalent cause of dementia (around 80% of all dementia cases) was not included as an outcome. Evidence shows CETP inhibition is unlikely to affect Alzheimer's risk and may even potentially modestly increase risk.
View Article and Find Full Text PDFThe aim of this study was to evaluate the lipid-lowering and plasma cholesteryl ester transfer protein(CETP) activity of (CL) and β-Sitosterol(βS) following intraperitoneal administration of Triton-WR 1339 (=Tyloxapol) (TWR) to male Wistar rats. Hyperlipidemia(HL) was developed by intraperitoneal injection of TWR. The animals were divided into main eight groups of six rats each.
View Article and Find Full Text PDFImmunotargets Ther
November 2024
Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China.
Background: Dyslipidemia has been implicated in the pathogenesis of several diseases, including thyroid dysfunction and immune disorders. However, whether circulating lipids and long-term use of lipid-lowering drugs influence the development of autoimmune thyroid disease (AITD) remains unclear. This study aims to evaluate the effects of lipid-lowering drugs on AITD and explore their potential mechanisms.
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