Cholesteryl Ester Transfer Protein Inhibitors and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Taheri, Hossein; Filion, Kristian B.; Windle, Sarah B.; Reynier, Pascal; Eisenberg, Mark J.

doi:10.1159/000505365

Cited by 40 publications

(30 citation statements)

References 31 publications

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“…CETP-inhibitors have mainly been investigated in other indications such as the treatment of hypercholesterolemia. A recent meta-analysis revealed that CETP inhibitors may reduce nonfatal myocardial infections or cardiovascular death, but the results did not reach statistical significance and the clinical relevance of these reductions is modest ( Taheri et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Impact of Sepsis on High-Density Lipoprotein Metabolism

Reisinger

Schüller

Sourij

et al. 2022

Front. Cell Dev. Biol.

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Background: High-density lipoproteins (HDL) are thought to play a protective role in sepsis through several mechanisms, such as promotion of steroid synthesis, clearing bacterial toxins, protection of the endothelial barrier, and antioxidant/inflammatory activities. However, HDL levels decline rapidly during sepsis, but the contributing mechanisms are poorly understood.Methods/Aim: In the present study, we investigated enzymes involved in lipoprotein metabolism in sepsis and non-sepsis patients admitted to the intensive care unit (ICU).Results: In 53 ICU sepsis and 25 ICU non-sepsis patients, we observed significant differences in several enzymes involved in lipoprotein metabolism. Lecithin-cholesterol acyl transferase (LCAT) activity, LCAT concentration, and cholesteryl transfer protein (CETP) activity were significantly lower, whereas phospholipid transfer activity protein (PLTP) and endothelial lipase (EL) were significantly higher in sepsis patients compared to non-sepsis patients. In addition, serum amyloid A (SAA) levels were increased 10-fold in sepsis patients compared with non-sepsis patients. Furthermore, we found that LCAT activity was significantly associated with ICU and 28-day mortality whereas SAA levels, representing a strong inflammatory marker, did not associate with mortality outcomes.Conclusion: We provide novel data on the rapid and robust changes in HDL metabolism during sepsis. Our results clearly highlight the critical role of specific metabolic pathways and enzymes in sepsis pathophysiology that may lead to novel therapeutics.

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Section: Introductionmentioning

confidence: 99%

Impact of Sepsis on High-Density Lipoprotein Metabolism

Reisinger

Schüller

Sourij

et al. 2022

Front. Cell Dev. Biol.

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“…CETP allows the transfer and exchange of neutral lipids such as CE (cholesteryl ester) and TG (triacylglycerol) between plasma and lipoproteins. It is proven to play important role in atherosclerosis [79]. Tomoda et al reported that chaetoviridin B (37) showed CETP (cholesteryl ester transfer protein) inhibitory activity with an IC 50 < 6.3 µM, whereas chaetoviridin A (31) had moderate inhibitory activity (IC 50 31.6 µM) [80].…”

Section: Cholesteryl Ester Transfer Protein Inhibitory Activitymentioning

confidence: 99%

Chaetomugilins and Chaetoviridins—Promising Natural Metabolites: Structures, Separation, Characterization, Biosynthesis, Bioactivities, Molecular Docking, and Molecular Dynamics

Omar

Mohamed

Ibrahim

2022

JoF

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Fungi are recognized as luxuriant metabolic artists that generate propitious biometabolites. Historically, fungal metabolites have largely been investigated as leads for various therapeutic agents. Chaetomugilins and the closely related chaetoviridins are fungal metabolites, and each has an oxygenated bicyclic pyranoquinone core. They are mainly produced by various Chaetomaceae species. These metabolites display unique chemical features and diversified bioactivities. The current review gives an overview of research about fungal chaetomugilins and chaetoviridins regarding their structures, separation, characterization, biosynthesis, and bioactivities. Additionally, their antiviral potential towards the SARS-CoV-2 protease was evaluated using docking studies and molecular dynamics (MD) simulations. We report on the docking and predictive binding energy estimations using reported crystal structures of the main protease (PDB ID: 6M2N, 6W81, and 7K0f) at variable resolutions—i.e., 2.20, 1.55, and 1.65 Å, respectively. Chaetovirdin D (43) exhibited highly negative docking scores of −7.944, −8.141, and −6.615 kcal/mol, when complexed with 6M2N, 6W81, and 7K0f, respectively. The reference inhibitors exhibited the following scores: −5.377, −6.995, and −8.159 kcal/mol, when complexed with 6M2N, 6W81, and 7K0f, respectively. By using molecular dynamics simulations, chaetovirdin D’s stability in complexes with the viral protease was analyzed, and it was found to be stable over the course of 100 ns.

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“…A recent meta-analysis of 11 randomized controlled trials [51] examined the effects of CETP inhibitors on major cardiovascular events (MACE) and all-cause mortality, showing a non-significant reduction in the risk of non-fatal myocardial infarction (−7%) and death from cardiovascular causes (−8%).…”

Section: Increasing Cholesterol In Hdl: Pharmacological Trialsmentioning

confidence: 99%

HDL in Atherosclerotic Cardiovascular Disease: In Search of a Role

Casula

Colpani

Xie

et al. 2021

Cells

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For a long time, high-density lipoprotein cholesterol (HDL-C) has been regarded as a cardiovascular disease (CVD) protective factor. Recently, several epidemiological studies, while confirming low plasma levels of HDL-C as an established predictive biomarker for atherosclerotic CVD, indicated that not only people at the lowest levels but also those with high HDL-C levels are at increased risk of cardiovascular (CV) mortality. This “U-shaped” association has further fueled the discussion on the pathophysiological role of HDL in CVD. In fact, genetic studies, Mendelian randomization approaches, and clinical trials have challenged the notion of HDL-C levels being causally linked to CVD protection, independent of the cholesterol content in low-density lipoproteins (LDL-C). These findings have prompted a reconsideration of the biological functions of HDL that can be summarized with the word “HDL functionality”, a term that embraces the many reported biological activities beyond the so-called reverse cholesterol transport, to explain this lack of correlation between HDL levels and CVD. All these aspects are summarized and critically discussed in this review, in an attempt to provide a background scenario for the “HDL story”, a lipoprotein still in search of a role.

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Cholesteryl Ester Transfer Protein Inhibitors and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Cited by 40 publications

References 31 publications

Impact of Sepsis on High-Density Lipoprotein Metabolism

Impact of Sepsis on High-Density Lipoprotein Metabolism

Chaetomugilins and Chaetoviridins—Promising Natural Metabolites: Structures, Separation, Characterization, Biosynthesis, Bioactivities, Molecular Docking, and Molecular Dynamics

HDL in Atherosclerotic Cardiovascular Disease: In Search of a Role

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