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Treatment with Statins Does Not Revert Trained Immunity in Patients with Familial Hypercholesterolemia

Siroon Bekkering1, Lotte C A Stiekema2, Sophie Bernelot Moens2

  • 1Department of Internal Medicine, and Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen 6525GA, the Netherlands; Department of Vascular Medicine, Amsterdam University Medical Centres, University of Amsterdam, 1105AZ Amsterdam, the Netherlands.

Cell Metabolism
|June 18, 2019
PubMed

Insights

Individuals with high LDL-cholesterol face cardiovascular risks. Familial hypercholesterolemia patients show trained immunity, which statins do not resolve, indicating persistent inflammation.

Area of Science:

  • Immunology
  • Cardiovascular Science
  • Metabolic Disorders

Background:

  • Elevated low-density lipoprotein (LDL)-cholesterol is a major risk factor for cardiovascular disease.
  • Current lipid-lowering strategies, including statins, reduce LDL-C but residual cardiovascular risk persists.
  • Familial hypercholesterolemia (FH) is a genetic disorder characterized by extremely high LDL-C levels.

Discussion:

  • Monocytes from FH patients exhibit a trained immunity phenotype, characterized by enhanced inflammatory responses.
  • This pro-inflammatory phenotype is linked to increased cardiovascular risk.
  • Lipid-lowering therapy with statins did not revert the trained immunity phenotype in FH monocytes.

Key Insights:

  • FH monocytes possess a persistent, trained immunity phenotype.
  • Statins, despite lowering LDL-C, do not reverse this pro-inflammatory cellular state.
  • Trained immunity may contribute to residual cardiovascular risk in FH patients.

Outlook:

  • Investigating novel therapeutic targets beyond LDL-C reduction is crucial.
  • Exploring interventions to modulate trained immunity in FH patients may reduce cardiovascular events.
  • Further research is needed to understand the long-term implications of trained immunity in metabolic diseases.

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