Effect of serial infusions of reconstituted high-density lipoprotein (CER-001) on coronary atherosclerosis: rationale and design of the CARAT study

Andrews, Jordan; Janssan, A.; Nguyen, Tracy; Pisaniello, Anthony D.; Scherer, Daniel; Kastelein, John J.P.; Merkely, Béla; Nissen, Steven E.; Ray, Kausik K.; Schwartz, Gregory G.; Worthley, Stephen G.; Keyserling, Constance H.; Dasseux, Jean-Louis; Butters, Julie; Girardi, Jacinta; Miller, Rosie; Nicholls, Stephen J.

doi:10.21037/cdt.2017.01.01

Cited by 51 publications

(31 citation statements)

References 51 publications

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“…Based on these observations, the effect of a 3 mg/kg CER-001 dose was evaluated in the CARAT study (NCT02484378) [ 39 ]. A total of 301 patients with status post ACS and a baseline percent atheroma volume > 30% in proximal 10 mm in a target vessel were randomized to receive 9 weeks of treatment with either low dose of CER-001 or placebo.…”

Section: Introductionmentioning

confidence: 99%

HDL Mimetics Infusion and Regression of Atherosclerosis: Is It Still Considered a Valid Therapeutic Option?

Karalis

Jukema

2018

Curr Cardiol Rep

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Purpose of ReviewThis review aims to summarize and discuss the recent findings in the field of using HDL mimetics for the treatment of patients with coronary artery disease.Recent FindingsFollowing the largely disappointing results with the cholesteryl ester transfer protein inhibitors, focus moved to HDL functionality rather than absolute HDL cholesterol values. A number of HDL/apoA-I mimicking molecules were developed, aiming to enhance reverse cholesterol transport that has been associated with an atheroprotective effect. Three HDL mimetics have made the step from bench-testing to clinical trials in humans and are discussed here: apoA-I Milano, CSL-112, and CER-001. Unfortunately, with the exception of CSL-112 where the results of the clinical trial are not yet known, none of the agents was able to demonstrate a clinical benefit.SummaryHDL mimetics have failed to date to prove a beneficial effect in clinical practice. Reverse cholesterol transport remains a challenging therapeutic pathway to be explored.

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Section: Introductionmentioning

confidence: 99%

HDL Mimetics Infusion and Regression of Atherosclerosis: Is It Still Considered a Valid Therapeutic Option?

Karalis

Jukema

2018

Curr Cardiol Rep

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“…There is currently ongoing interest in the infusion of HDL particles or HDL mimetics to promote plaque regression [ 8 , 48 , 49 ]. This study suggests that some patterns of dosage will be more successful than others.…”

Section: Discussionmentioning

confidence: 99%

“…Large clinical trails have commenced for infusion of HDL mimetics have the application of gene therapy as treatment for late stage plaques [ 48 , 49 , 51 ]. Preliminary results suggest that regular, ongoing infusions of a HDL mimetic can reduce the area of a plaque by about 6.7% on average [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Nonlinear dynamics of early atherosclerotic plaque formation may determine the efficacy of high density lipoproteins (HDL) in plaque regression

2017

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We use a computational model to explore the effect of foam cell accumulation on plaque regression following an increase in high density lipoprotein (HDL) influx into the plaque. Atherosclerotic plaque formation is the outcome of cellular and cytokine responses to low density lipoproteins (LDL) that penetrate the artery wall following an injury to the endothelium and become modified. We modelled the cells and cytokines that are most important in plaque formation using partial differential equations. The model includes monocytes and macrophages, foam cells, macrophage chemoattractants, endothelium-stimulating cytokines, modified low density lipoproteins (mod LDL) and HDL. We included interactions both at the endothelium surface and inside the artery wall. The model predicts that when HDL influx into a well-established plaque with large numbers of foam cells is increased, the plaque may not regress but may continue to grow at a slower rate. If HDL influx is increased when a model plaque is recently established and has fewer foam cells, then the plaque does regress. If modLDL influx into the plaque is lowered at the same time that HDL influx increased or the capacity of the HDL to remove cholesterol from foam cells is increased, then the plaque is more likely to regress. The predictions of the model are in qualitative agreement with experimental studies in mice and rabbits. The results suggest that the intrinsic dynamics of reverse cholesterol transport by HDL are important in determining the success of HDL raising in promoting plaque regression.

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“…Animal studies show that raising an apoA1 and functional HDL can promote atherosclerosis plaque regression through inhibition of inflammation and decreased activation of immune cells (116). Larger trials paint a more controversial story, showing no detectable effect after supplementation of an engineered pre-β HDL mimetic on atherosclerotic plaque composition or regression compared to placebo (117).…”

Section: Hdl-based Therapiesmentioning

confidence: 99%

High Density Lipoproteins: Metabolism, Function, and Therapeutic Potential

Jomard

Osto

2020

Front. Cardiovasc. Med.

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High Density Lipoproteins (HDLs) have long been considered as "good cholesterol," beneficial to the whole body and, in particular, to cardio-vascular health. However, HDLs are complex particles that undergoes dynamic remodeling through interactions with various enzymes and tissues throughout their life cycle, making the complete understanding of its functions and roles more complicated than initially expected. In this review, we explore the novel understanding of HDLs' behavior in health and disease as a multifaceted class of lipoprotein, with different size subclasses, molecular composition, receptor interactions, and functionality. Further, we report on emergent HDL-based therapeutics tested in small and larger scale clinical trials and their mixed successes.

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Effect of serial infusions of reconstituted high-density lipoprotein (CER-001) on coronary atherosclerosis: rationale and design of the CARAT study

Cited by 51 publications

References 51 publications

HDL Mimetics Infusion and Regression of Atherosclerosis: Is It Still Considered a Valid Therapeutic Option?

HDL Mimetics Infusion and Regression of Atherosclerosis: Is It Still Considered a Valid Therapeutic Option?

Nonlinear dynamics of early atherosclerotic plaque formation may determine the efficacy of high density lipoproteins (HDL) in plaque regression

High Density Lipoproteins: Metabolism, Function, and Therapeutic Potential

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