CETP

Cholesteryl ester transfer protein (CETP) is a promising therapeutic target for cardiovascular diseases. It effectively lowers the low-density lipoprotein cholesterol levels and increases the high-density lipoprotein cholesterol levels in the human plasma. This study identified novel and highly potent CETP inhibitors using virtual screening techniques. Molecular docking and molecular dynamics (MD) simulations revealed the binding patterns of these inhibitors, with the top 50 compounds selected according to their predicted binding affinity...

BACKGROUND: Several studies assessed the relationship between the cholesterol ester transfer protein (CETP) Taq1B gene polymorphism (rs708272) with risk factors of cardiovascular diseases (CVDs). However, their findings were inconsistent. The present study investigated the relationship between CVD risk factors and the Taq1B variant in patients undergoing coronary angiography. METHODS: This cross-sectional study was conducted on 476 patients aged 30-76 years old of both sexes from 2020-2021, in Yazd (Iran)...

Patients with atherosclerotic disease remain at increased risk of future events despite receiving optimal medical treatment. This residual risk is widely heterogeneous, but lipoprotein particles and their content play a major role in determining future cardiovascular events. Beyond low-density lipoprotein cholesterol (LDL-c), other lipoprotein particles have not demonstrated similar contribution to the progression of atherosclerosis. Statins, ezetimibe, and more recently, proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors and bempedoic acid have confirmed the causal role of LDL-c in the development of atherosclerosis...

BACKGROUND: Atherosclerosis is the major underlying pathology of cardiovascular disease and is driven by dyslipidemia and inflammation. Inhibition of the immunoproteasome, a proteasome variant that is predominantly expressed by immune cells and plays an important role in antigen presentation, has been shown to have immunosuppressive effects. METHODS: We assessed the effect of ONX-0914, an inhibitor of the immunoproteasomal catalytic subunits LMP7 (proteasome subunit β5i/large multifunctional peptidase 7) and LMP2 (proteasome subunit β1i/large multifunctional peptidase 2), on atherosclerosis and metabolism in LDLr-/- and APOE*3-Leiden...

Sepsis is a leading cause of mortality worldwide, and pneumonia is the most common cause of sepsis in humans. Low levels of high-density lipoprotein cholesterol (HDL-C) levels are associated with an increased risk of death from sepsis, and increasing levels of HDL-C by inhibition of cholesteryl ester transfer protein (CETP) decreases mortality from intraabdominal polymicrobial sepsis in APOE*3-Leiden.CETP mice. Here, we show that treatment with the CETP inhibitor (CETPi) anacetrapib reduced mortality from Streptococcus pneumoniae-induced sepsis in APOE*3-Leiden...

Imagine consuming a daily diet rich in fatty acids to help treat diseases such as hypertension and obesity. This concept presents an attractive paradox. In particular, consuming walnut kernels is beneficial for treating diseases associated with metabolic syndrome (MetS), including type 2 diabetes, cardiovascular disease, dyslipidemia, and obesity. Different parts of the Juglans regia tree (family Juglandaceae), including its leaves, green husks, bark, and septum, have shown promising effects on pathological conditions related to MetS...

Cumulative exposure to low-density lipoprotein cholesterol (LDL-C) is a key driver of atherosclerotic cardiovascular disease (ASCVD) risk. An armamentarium of therapies to achieve robust and sustained reduction in LDL-C can reduce ASCVD risk. The gold standard for LDL-C assessment is ultracentrifugation but in routine clinical practice LDL-C is usually calculated and the most accurate calculation is the Martin/Hopkins equation. For primary prevention, consideration of estimated ASCVD risk frames decision making regarding use of statins and other therapies, and tools such as risk enhancing factors and coronary artery calcium enable tailoring of risk assessment and decision making...

AIMS: Obicetrapib is a highly selective cholesteryl ester transfer protein (CETP) inhibitor shown to reduce low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB), when taken as monotherapy and in combination with ezetimibe on a background of statins, in clinical trials predominantly conducted in Northern European/Caucasian participants. We characterized the efficacy, safety, and tolerability of obicetrapib within an Asian-Pacific region population. METHODS: This double-blind, randomized, phase 2 trial examined obicetrapib 2...

BACKGROUND: Obstructive sleep apnea (OSA) is considered to be an important contributor of dyslipidemia. However, there lacks observational studies focusing on the potential effect of lipid management on OSA risk. Thus, we aimed to investigate the genetic association of lipid-modifying therapy with risk of OSA. METHODS: A drug-target mendelian randomization (MR) study using both cis-variants and cis-expression quantitative trait loci (eQTLs) of lipid-modifying drug targets was performed...

BACKGROUND: Coronary artery disease (CAD) is a devastating illness and a leading cause of death worldwide, primarily caused by atherosclerosis resulting from a genetic-environmental interaction. This study aimed to investigate the relationship between the ESR1 (rs9340799), OLR1 (rs3736234), LIPC (rs2070895), VDR (rs2228570), and CETP (rs708272) polymorphisms, lipid profile parameters, and CAD risk in a southeast Iranian population. METHODS: A total of 400 subjects (200 CAD patients with hyperlipidemia and 200 healthy controls) were enrolled in this case-control study...

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor response to all therapeutic modalities and dismal prognosis. The presence of tertiary lymphoid structures (TLSs) in various solid cancers is of crucial prognostic significance, highlighting the intricate interplay between the tumor microenvironment and immune cells aggregation. However, the extent to which TLS and immune status affect PDAC prognosis remains incompletely understood. Here, we sought to unveil the unique properties of TLS in PDAC by leveraging both single-cell and bulk transcriptomics, and culminating in a risk model that predicts clinical outcomes...

OBJECTIVE: Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus (DM) that is closely related to aging. In this study, we found co-differential genes between DKD and aging and established a diagnostic model of DKD based on these genes. METHODS: Differentially expressed genes (DEGs) in DKD were screened using GEO datasets. The intersection of the DEGs of DKD and aging-related genes revealed DKD and aging co-differential genes. Based on this, a genetic diagnostic model for DKD was constructed using LASSO regression...

BACKGROUND: Breast cancer (BC) is the most common and fatal cancer among women, yet the causal relationship between circulating lipids, lipid-lowering drugs, and BC remains unclear. METHODS: Mendelian randomization (MR) and summary data-based MR (SMR) analysis are used to explore the causal relationship between plasma lipids, lipid-lowering drug targets, and BC. RESULTS: The result of MR suggested that per mg/dL higher levels of LDL-C (OR = 1...

Cardiovascular disease, the primary cause of human mortality globally, is predominantly caused by a progressive disorder known as atherosclerosis. Atherosclerosis refers to the process of accumulation of cholesterol-enriched lipoproteins and the concomitant initiation of inflammatory processes in the arterial wall, including recruitment of immune cells. This leads to the formation of atherosclerotic plaques, initially causing a thickening of the arterial wall and narrowing of arteries. However, as plaque formation progresses, atherosclerotic plaques may become unstable and rupture, leading to a blood clot that blocks the affected artery or travels through the blood to block blood flow elsewhere...

Lipid metabolism plays an essential role in the pathogenesis of cardiovascular and metabolic diseases. Cholesteryl ester transfer protein (CETP) is a crucial glycoprotein involved in lipid metabolism by transferring cholesteryl esters (CE) and triglycerides (TG) between plasma lipoproteins. CETP activity results in reduced HDL-C and increased VLDL- and LDL-C concentrations, thus increasing the risk of cardiovascular and metabolic diseases. In this review, we discuss the structure of CETP and its mechanism of action...

BACKGROUND: Hyperlipidemia is characterized by an abnormally elevated serum cholesterol, triglycerides, or both. The relationship between an elevated level of LDL and cardiovascular diseases is well-established. Cholesteryl ester transfer protein (CETP) is an enzyme that moves cholesterol esters and triglycerides between LDL, VLDL, and HDL. CETP inhibition leads to a reduction in cardiovascular disease by raising HDL and minimizing LDL. OBJECTIVE: This study synthesized ten meta-chlorinated benzene sulfonamides 6a-6j and explored their structure-activity relationship...

BACKGROUND: Biomarkers of early pathogenesis of type 1 diabetes (T1D) are crucial to enable effective prevention measures in at-risk populations before significant damage occurs to their insulin producing beta-cell mass. We recently introduced the concept of integrated parallel multi-omics and employed a novel data augmentation approach which identified promising candidate biomarkers from a small cohort of high-risk T1D subjects. We now validate selected biomarkers to generate a potential composite signature of T1D risk...

The COVID-19 pandemic, triggered by severe acute respiratory syndrome coronavirus 2, has affected millions of people worldwide. Much research has been dedicated to our understanding of COVID-19 disease heterogeneity and severity, but less is known about recovery associated changes. To address this gap in knowledge, we quantified the proteome from serum samples from 29 COVID-19 convalescents and 29 age-, race-, and sex-matched healthy controls. Samples were acquired within the first months of the pandemic. Many proteins from pathways known to change during acute COVID-19 illness, such as from the complement cascade, coagulation system, inflammation and adaptive immune system, had returned to levels seen in healthy controls...

Chronic low degree inflammation is a hallmark of atherosclerotic cardiovascular disease. To assess the effect of lipid-lowering therapies (LLTs) on C-reactive protein (CRP), a biomarker of inflammation, we conducted a meta-analysis according to the PRISMA guidelines. Databases were searched from inception to July 2023. Inclusion criteria were: (1) randomized controlled trials (RCTs) in human, phase II, III or IV; (2) English language; (3) comparing the effect of lipid-lowering drugs vs placebo; (4) reporting the effects on CRP levels; (5) with intervention duration of more than 3 weeks; (6) and sample size (for both intervention and control group) over than 100 subjects...

The association of CETP Taq1B polymorphism with some metabolic traits is still controversial. The interaction of adherence to dietary indices with this polymorphism on the severity of coronary artery stenosis and serum lipid parameters needs to be investigated. This study aimed to test this hypothesis. This cross-sectional study included 453 patients who were referred from Afshar Hospital of Yazd and undergoing coronary angiography from 2020 to 2021. Dietary intake was evaluated by a 178-item validated and reliable dietary questionnaire...