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Trained immunity in cardiovascular disease.

Niels P Riksen1, Mihai G Netea1,2, Hafid Ait-Oufella3,4

  • 1Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 8, Nijmegen 6525 GA, The Netherlands.

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Summary
This summary is machine-generated.

Trained immunity (TRIM), a hyperinflammatory immune cell state, can be triggered by cardiovascular disease risk factors. Targeting TRIM pathways in myeloid cells offers a novel strategy for preventing and treating cardiovascular events.

Keywords:
AtherosclerosisCardiovascular diseaseInflammationInnate immune memoryMonocytesTrained immunityTrained innate immunity

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Area of Science:

  • Immunology
  • Cardiovascular Medicine
  • Metabolic and Epigenetic Regulation

Background:

  • Innate immunity plays a crucial role in atherosclerosis development.
  • Trained immunity (TRIM) is a long-term hyperinflammatory immune phenotype involving metabolic and epigenetic changes.
  • TRIM can affect both mature immune cells and non-immune cells, as well as hematopoietic stem cells.

Purpose of the Study:

  • To explore the role of trained immunity (TRIM) in cardiovascular disease (CVD) pathophysiology.
  • To identify novel pharmacological targets for CVD prevention and treatment based on TRIM mechanisms.

Main Methods:

  • Experimental studies in mice investigating TRIM induction by CVD risk factors.
  • Analysis of cellular metabolism (glycolysis, glutaminolysis) and epigenetic modifications (histone methylation, acetylation, lactylation).
  • Focus on IL-1β signaling in the bone marrow as a driver of central TRIM.

Main Results:

  • Central TRIM can be induced by various CVD risk factors, including obesity, hyperglycemia, hypertension, inflammatory comorbidities, and lifestyle factors.
  • Induced TRIM leads to a long-term presence of hyperinflammatory monocytes and neutrophils, accelerating atherosclerosis.
  • IL-1β signaling in the bone marrow and metabolic/epigenetic rewiring are key mechanisms driving TRIM development.

Conclusions:

  • Trained immunity is implicated in the pathophysiology of cardiovascular disease.
  • Pharmacological targeting of TRIM pathways in myeloid cells presents a promising new therapeutic strategy for cardiovascular events.