keyword
https://read.qxmd.com/read/36047191/evacetrapib-elicits-antitumor-effects-on-colorectal-cancer-by-inhibiting-the-wnt-%C3%AE-catenin-signaling-pathway-and-activating-the-jnk-signaling-pathway
#1
JOURNAL ARTICLE
Limei Hu, Haiyan Dong, Lingyuan He, Mengchen Shi, Nanlin Xiang, Yixi Su, Chen Wang, Yu Tian, Yijia Hu, Huihui Wang, Huanliang Liu, Chuangyu Wen, Xiangling Yang
Despite advances in colorectal cancer (CRC) treatment, most advanced CRC patients who experience disease progression after chemotherapy, targeted therapy, and immunotherapy face a situation in which there is no available medicine. Thus, new therapeutic drugs for CRC are urgently needed. Studies have shown that cholesteryl ester transfer protein (CETP) has a vital role in tumor development and is a possible target for CRC therapy. We found that Evacetrapib, a CETP inhibitor, suppressed CRC cell growth by inhibiting the Wnt/β-catenin signaling pathway and activating the c-Jun NH2-terminal kinase (JNK) signaling pathway in CRC...
2022: Biological & Pharmaceutical Bulletin
https://read.qxmd.com/read/35970631/longitudinal-high-sensitivity-c-reactive-protein-and-longer-term-cardiovascular-outcomes-in-optimally-treated-patients-with-high-risk-vascular-disease
#2
JOURNAL ARTICLE
Iryna Dykun, Donald Clark, Julie Carlo, A Michael Lincoff, Venu Menon, Steven E Nissen, Stephen J Nicholls, Rishi Puri
The relation between serial high-sensitivity C-reactive protein (hsCRP) and long-term major cardiovascular events (MACEs; cardiovascular death, myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina) has not been explored in optimally-treated patients with atherosclerotic cardiovascular disease. We tested the hypothesis that longitudinal follow-up hsCRP (repeated measures over time) would associate with 30-month MACE rates. We performed a post hoc analysis of ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibitor with Evacetrapib in Patients with High-Risk for Vascular Outcomes), involving optimally-treated patients with high-risk vascular disease, with available baseline and at least 1 follow-up hsCRP level...
August 12, 2022: American Journal of Cardiology
https://read.qxmd.com/read/35941608/high-affinity-soat1-ligands-remodeled-cholesterol-metabolism-program-to-inhibit-tumor-growth
#3
JOURNAL ARTICLE
Zhihua Wang, Miaomiao Wang, Mengxin Zhang, Kaikun Xu, Xinshuai Zhang, Yi Xie, Yiming Zhang, Cheng Chang, Xiaolu Li, Aihua Sun, Fuchu He
BACKGROUND: Although cholesterol metabolism is a common pathway for the development of antitumor drugs, there are no specific targets and drugs for clinical use. Here, based on our previous study of sterol O-acyltransferase 1 (SOAT1) in hepatocelluar carcinoma, we sought to screen an effective targeted drug for precise treatment of hepatocelluar carcinoma and, from the perspective of cholesterol metabolism, clarify the relationship between cholesterol regulation and tumorigenesis and development...
August 9, 2022: BMC Medicine
https://read.qxmd.com/read/35109032/cholesterol-metabolism-in-alzheimer-s-disease
#4
JOURNAL ARTICLE
Jasmine Phenix, Felix Oestereich, Lisa-Marie Munter
BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia and affects around 24 million individuals worldwide. Several studies showed an association between high plasma low-density lipoprotein (LDL) levels and an increased risk of developing AD. To that effect, multiple drugs treating hypercholesterolaemia, such as statins, have been tested to prevent AD. In this study, we propose a new pharmacological target called Cholesteryl Ester Transfer Protein (CETP). In recent years, studies have shown an association between different genetic variants of CETP and the risk of developing AD...
December 2021: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://read.qxmd.com/read/34937388/pharmacological-inhibition-of-cetp-cholesteryl-ester-transfer-protein-increases-hdl-high-density-lipoprotein-that-contains-apoc3-and-other-hdl-subspecies-associated-with-higher-risk-of-coronary-heart-disease
#5
RANDOMIZED CONTROLLED TRIAL
Jeremy D Furtado, Giacomo Ruotolo, Stephen J Nicholls, Robert Dullea, Santos Carvajal-Gonzalez, Frank M Sacks
OBJECTIVE: Plasma total HDL (high-density lipoprotein) is a heterogeneous mix of many protein-based subspecies whose functions and associations with coronary heart disease vary. We hypothesize that increasing HDL by CETP (cholesteryl ester transfer protein) inhibition failed to reduce cardiovascular disease risk, in part, because it increased dysfunctional subspecies associated with higher risk such as HDL that contains apoC3. Approach and Results: We studied participants in 2 randomized, double-blind, placebo-controlled trials of a CETP inhibitor on a background of atorvastatin treatment: ACCENTUATE (The Addition of Evacetrapib to Atorvastatin Compared to Placebo, High Intensity Atorvastatin, and Atorvastatin With Ezetimibe to Evaluate LDL-C Lowering in Patients With Primary Hyperlipidemia; 130 mg evacetrapib; n=126) and ILLUMINATE (Phase 3 Multi Center, Double Blind, Randomized, Parallel Group Evaluation of the Fixed Combination Torcetrapib/Atorvastatin, Administered Orally, Once Daily [Qd], Compared With Atorvastatin Alone, on the Occurrence of Major Cardiovascular Events in Subjects With Coronary Heart Disease or Risk Equivalents; 60 mg torcetrapib; n=80)...
February 2022: Arteriosclerosis, Thrombosis, and Vascular Biology
https://read.qxmd.com/read/34849601/cetp-inhibitors-from-hdl-c-to-ldl-c-lowering-agents
#6
JOURNAL ARTICLE
Nick S Nurmohamed, Marc Ditmarsch, John J P Kastelein
Cholesteryl ester transfer protein (CETP) is a liver-synthesized glycoprotein whose main functions are facilitating transfer of both cholesteryl esters from high-density lipoprotein (HDL) particles to apolipoprotein B containing (apoB) particles as well as transfer of triglycerides from apoB containing particles to HDL particles. Novel crystallographic data have shown that CETP exchanges lipids in the circulation by a dual molecular mechanism. Recently, it has been suggested that the atherosclerotic cardiovascular disease (ASCVD) benefit from CETP inhibition is the consequence of the achieved low-density lipoprotein cholesterol (LDL-C) and apoB reduction, rather than through the HDL-C increase...
November 26, 2021: Cardiovascular Research
https://read.qxmd.com/read/33882411/safety-and-efficacy-of-evacetrapib-in-patients-with-inadequately-controlled-hypercholesterolemia-and-high-cardiovascular-risk-a-meta-analysis-of-randomized-placebo-controlled-trials
#7
REVIEW
Eshak I Bahbah, Mohamed S A Shehata, Safwat Ibrahim Alnahrawi, Ahmed Sayed, Amr Menshawey, Ahmed Fisal, Mahmoud Morsi, Mohamed Essam Gabr, Mohamed Salah Abd Elbasit
BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is causally related to cardiovascular disease. Inhibition of cholesteryl ester transfer protein with Evacetrapib may provide an additional treatment option for patients who do not reach their LDL-C goal with statins or patients who cannot tolerate statins. We aimed to evaluate the safety and efficacy of Evacetrapib in patients with inadequately-controlled hypercholesterolemia and high cardiovascular risk. METHOD: A computer literature search for PubMed, Scopus, and Science Direct was carried out from inception to 2019 and was updated from January 2019 till March 2021...
April 12, 2021: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://read.qxmd.com/read/32941836/cholesteryl-ester-transfer-protein-inhibitors-in-precision-medicine
#8
REVIEW
Xin Su, Guiyang Li, Yingjian Deng, Dong Chang
Dyslipidemia is associated with atherosclerosis and cardiovascular disease development, posing serious risks to human health. Cholesteryl ester transfer protein (CETP) is responsible for exchange of neutral lipids, such as cholesteryl ester and TG, between plasma high density lipoprotein (HDL) particles and Apolipoprotein B-100 (ApoB-100) containing lipoprotein particles. Genetic studies suggest that single-nucleotide polymorphism (SNPs) with loss of activity CETP is associated with increased HDL-C, reduced LDL-C, and cardiovascular risk...
September 14, 2020: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://read.qxmd.com/read/32639518/effect-of-c-reactive-protein-on-lipoprotein-a-associated-cardiovascular-risk-in-optimally-treated-patients-with-high-risk-vascular-disease-a-prespecified-secondary-analysis-of-the-accelerate-trial
#9
JOURNAL ARTICLE
Rishi Puri, Steven E Nissen, Benoit J Arsenault, Julie St John, Jeffrey S Riesmeyer, Giacomo Ruotolo, Ellen McErlean, Venu Menon, Leslie Cho, Kathy Wolski, A Michael Lincoff, Stephen J Nicholls
Importance: Although lipoprotein(a) (Lp[a]) is a causal genetic risk factor for atherosclerotic cardiovascular disease, it remains unclear which patients with established atherosclerotic cardiovascular disease stand to benefit the most from Lp(a) lowering. Whether inflammation can modulate Lp(a)-associated cardiovascular (CV) risk during secondary prevention is unknown. Objective: To examine whether Lp(a)-associated CV risk is modulated by systemic inflammation in optimally treated patients at high risk of CV disease...
October 1, 2020: JAMA Cardiology
https://read.qxmd.com/read/32200670/the-mystery-of-evacetrapib-why-are-cetp-inhibitors-failing
#10
EDITORIAL
Stephen J Nicholls, Kristen Bubb
No abstract text is available yet for this article.
March 21, 2020: Expert Review of Cardiovascular Therapy
https://read.qxmd.com/read/32179516/effect-of-cetp-inhibition-with-evacetrapib-in-patients-with-diabetes-mellitus-enrolled-in-the-accelerate-trial
#11
JOURNAL ARTICLE
Venu Menon, Anirudh Kumar, Divyang R Patel, Julie St John, Jeffrey Riesmeyer, Govinda Weerakkody, Giacomo Ruotolo, Kathy E Wolski, Ellen McErlean, Paul C Cremer, Stephen J Nicholls, A Michael Lincoff, Steven E Nissen
BACKGROUND: High-density lipoprotein (HDL) levels are inversely associated with cardiovascular risk. Cholesteryl ester transfer protein inhibition with evacetrapib results in a marked increase in HDL and reduction in low-density lipoprotein (LDL) levels. We evaluated the impact of treatment with evacetrapib versus placebo in the subset of 8236 patients with diabetes mellitus (DM) enrolled in the Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes trial...
March 2020: BMJ Open Diabetes Research & Care
https://read.qxmd.com/read/32172237/cholesteryl-ester-transfer-protein-inhibitors-and-cardiovascular-outcomes-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#12
Hossein Taheri, Kristian B Filion, Sarah B Windle, Pauline Reynier, Mark J Eisenberg
BACKGROUND: Cholesteryl ester transfer protein (CETP) inhibitors increase serum high-density lipoprotein cholesterol (HDL-c) concentration; however, their impact on cardiovascular outcomes is not clear. This systematic review examines the effect of CETP inhibitors on serum lipid profiles, cardiovascular events, and all-cause mortality. METHODS: We searched MEDLINE, Embase, and the Cochrane Library of Clinical Trials for placebo-controlled randomized controlled trials (RCTs) that examined the effect of a CETP inhibitor (dalcetrapib, anacetrapib, evacetrapib, or TA-8995) on all-cause mortality, major adverse cardiovascular events (MACE), or the components of MACE at ≥6 months...
March 13, 2020: Cardiology
https://read.qxmd.com/read/31898914/genome-wide-polygenic-score-and-cardiovascular-outcomes-with-evacetrapib-in-patients-with-high-risk-vascular-disease-a-nested-case-control-study
#13
EDITORIAL
Connor A Emdin, Pallav Bhatnagar, Minxian Wang, Sreekumar G Pillai, Lin Li, Hui-Rong Qian, Jeffrey S Riesmeyer, A Michael Lincoff, Stephen J Nicholls, Steven E Nissen, Giacomo Ruotolo, Sekar Kathiresan, Amit V Khera
Genome-wide polygenic scores (GPSs) integrate information from many common DNA variants into a single measure of inherited susceptibility, and can identify individuals who are at substantially elevated risk of developing important common diseases. For coronary artery disease, about 8% of the population can be identified who are at triple the normal risk based on genetic variation alone. Among these high polygenic score individuals, adherence to a healthy lifestyle or use of statins may offset increased inherited risk...
January 3, 2020: Circulation. Genomic and Precision Medicine
https://read.qxmd.com/read/31852422/impact-of-baseline-glycemic-control-on-residual-cardiovascular-risk-in-patients-with-diabetes-mellitus-and-high-risk-vascular-disease-treated-with-statin-therapy
#14
JOURNAL ARTICLE
Venu Menon, Anirudh Kumar, Divyang R Patel, Julie St John, Kathy E Wolski, Ellen McErlean, Jeffrey S Riesmeyer, Govinda Weerakkody, Giacomo Ruotolo, Paul C Cremer, Stephen J Nicholls, A Michael Lincoff, Steven E Nissen
Background The contemporary impact of glycemic control on patients with diabetes mellitus at high cardiovascular risk remains unclear. We evaluated the utility of hemoglobin A1c (HbA1c) as a marker of risk on the composite end point of cardiovascular death, nonfatal myocardial infarction, stroke, hospitalization for unstable angina, and coronary revascularization in an optimally treated population with diabetes mellitus and established coronary artery disease enrolled in the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial...
January 7, 2020: Journal of the American Heart Association
https://read.qxmd.com/read/31752637/plasma-aldosterone-levels-are-not-associated-with-cardiovascular-events-among-patients-with-high-risk-vascular-disease-insights-from-the-accelerate-trial
#15
JOURNAL ARTICLE
Anirudh Kumar, Divyang R Patel, Danielle M Brennan, Kathy E Wolski, A Michael Lincoff, Giacomo Ruotolo, Ellen McErlean, Govinda Weerakkody, Jeffrey S Riesmeyer, Stephen J Nicholls, Steven E Nissen, Venu Menon
Background The failure of cholesteryl ester transfer protein inhibitor torcetrapib was associated with an off-target increase in plasma aldosterone. We sought to evaluate the impact of evacetrapib on plasma aldosterone level and determine the association between plasma aldosterone level and major adverse cardiovascular events among patients with stable high-risk vascular disease enrolled in the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial...
December 3, 2019: Journal of the American Heart Association
https://read.qxmd.com/read/31054484/evacetrapib-reduces-pre%C3%AE-1-hdl-in-patients-with-atherosclerotic-cardiovascular-disease-or-diabetes
#16
JOURNAL ARTICLE
Yunqin Chen, Jibin Dong, Xiaojin Zhang, Xueying Chen, Li Wang, Haozhu Chen, Junbo Ge, Xian-Cheng Jiang
BACKGROUND AND AIMS: Cholesteryl ester transfer protein (CETP) inhibitor-mediated induction of HDL-cholesterol has no effect on the protection from cardiovascular disease (CVD). However, the mechanism is still unknown. Data on the effects of this class of drugs on subclasses of HDL are either limited or insufficient. In this study, we investigated the effect of evacetrapib, a CETP inhibitor, on subclasses of HDL in patients with atherosclerotic cardiovascular disease or diabetes. METHODS: Baseline and 3-month post-treatment samples from atorvastatin 40 mg plus evacetrapib 130 mg (n = 70) and atorvastatin 40 mg plus placebo (n = 30) arms were used for this purpose...
April 14, 2019: Atherosclerosis
https://read.qxmd.com/read/31014095/baseline-fasting-plasma-insulin-levels-predict-risk-for-major-adverse-cardiovascular-events-among-patients-with-diabetes-and-high-risk-vascular-disease-insights-from-the-accelerate-trial
#17
JOURNAL ARTICLE
Anirudh Kumar, Divyang R Patel, Kathy E Wolski, A Michael Lincoff, Sangeeta R Kashyap, Giacomo Ruotolo, Ellen McErlean, Govinda Weerakkody, Jeffrey S Riesmeyer, Stephen J Nicholls, Steven E Nissen, Venu Menon
BACKGROUND: Despite optimal treatment, type II diabetes mellitus remains associated with an increased risk for future cardiovascular events. We sought to determine the association between baseline fasting plasma insulin levels and major adverse cardiovascular outcomes in patients with type II diabetes mellitus and high-risk vascular disease enrolled in the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial...
March 2019: Diabetes & Vascular Disease Research
https://read.qxmd.com/read/30704580/cholesteryl-ester-transfer-protein-inhibition-for-preventing-cardiovascular-events-jacc-review-topic-of-the-week
#18
REVIEW
Jane Armitage, Michael V Holmes, David Preiss
Cholesteryl ester transfer protein (CETP) facilitates exchange of triglycerides and cholesteryl ester between high-density lipoprotein (HDL) and apolipoprotein B100-containing lipoproteins. Evidence from genetic studies that variants in the CETP gene were associated with higher blood HDL cholesterol, lower low-density lipoprotein cholesterol, and lower risk of coronary heart disease suggested that pharmacological inhibition of CETP may be beneficial. To date, 4 CETP inhibitors have entered phase 3 cardiovascular outcome trials...
February 5, 2019: Journal of the American College of Cardiology
https://read.qxmd.com/read/30347344/cholesteryl-ester-transfer-protein-an-enigmatic-pharmacology-antagonists-and-agonists
#19
REVIEW
Shizuya Yamashita, Massimiliano Ruscica, Chiara Macchi, Alberto Corsini, Yuji Matsuzawa, Cesare R Sirtori
The cholesteryl ester transfer protein (CETP) system moves cholesteryl esters (CE) from high density lipoproteins (HDL) to lower density lipoproteins, i.e. very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) in exchange for triglycerides (TGs). This shuttle process will ultimately form complexes facilitating a bidirectional exchange of CE and TGs, the end process being CE delivery to catabolic sites. The CETP system is generally characteristic of higher animal species; lower species, not provided with this system, have higher and enlarged HDL enriched with apo E, suitable for tissue receptor interaction...
October 1, 2018: Atherosclerosis
https://read.qxmd.com/read/29630000/what-have-we-learnt-from-the-clinical-outcomes-trials-with-the-cetrapibs
#20
JOURNAL ARTICLE
Sheila A Doggrell
PURPOSE OF REVIEW: The current review considers what we have learnt from the clinical outcome trials with the cetrapibs; the inhibitors of cholesteryl ester transfer protein that increase HDL cholesterol levels; torcetrapib, dalcetrapib, evacetrapib and anacetrapib. RECENT FINDINGS: Although an off-target increase in blood pressure may have contributed to the failure of torcetrapib in Investigation of Lipid Level Management to Understand its Impact in Atherosclerotics Events, recent evidence shows that torcetrapib also increased atherogenic apoproteins, and this may have contributed to its failure...
August 2018: Current Opinion in Lipidology
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