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New Therapies for Lowering Triglyceride-Rich Lipoproteins: JACC Focus Seminar 3/4

Robert S Rosenson1, Aleesha Shaik1, Wenliang Song2

  • 1Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Journal of the American College of Cardiology
|October 29, 2021
PubMed

Insights

Elevated triglyceride-rich lipoprotein remnants (TRLs) increase cardiovascular risk. New therapies targeting TRL metabolism show promise for managing this risk, but clinical trials are needed.

Area of Science:

  • Cardiovascular Science
  • Metabolic Research
  • Lipid Metabolism

Background:

  • Elevated triglyceride-rich lipoprotein remnants (TRLs) from liver and gut sources are linked to atherosclerotic cardiovascular events.
  • Genetic studies indicate a causal relationship between remnant cholesterol and atherosclerotic cardiovascular disease (ASCVD) risk.
  • Perturbations in metabolic pathways regulating TRLs contribute to ASCVD.

Purpose of the Study:

  • To review the role of TRLs in atherosclerotic cardiovascular disease.
  • To discuss emerging therapies targeting TRL metabolism for cardiovascular risk management.
  • To highlight the need for clinical trials on novel TRL-targeting agents.

Main Methods:

  • Review of emerging evidence on TRLs and cardiovascular risk.
  • Analysis of natural selection studies supporting a causal link.
  • Evaluation of experimental models and patient data for TRL-lowering therapies.

Main Results:

  • TRLs are implicated in atherosclerotic cardiovascular events.
  • Targeting catalytic pathways in TRL metabolism reduces atherosclerosis in experimental settings.
  • TRL concentrations vary widely in patients, suggesting broad therapeutic potential.

Conclusions:

  • Emerging therapies targeting angiopoietin-like 3 protein and apolipoprotein C-III warrant further investigation.
  • Clinical trials are essential to determine the role of these therapies in managing cardiovascular risk in patients with elevated remnant cholesterol.
  • These novel therapies may offer a new paradigm for cardiovascular risk management.
Keywords:
angiopoietin-like 3 protein inhibitorsapolipoprotein C-III inhibitorseicosapentaenoic acidomega-3 fatty acidstriglyceride-rich lipoproteinstriglycerides

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