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mTOR Inhibition and Cardiovascular Diseases: Dyslipidemia and Atherosclerosis

Ammar Kurdi1, Wim Martinet1, Guido R Y De Meyer1

  • 1Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.

Transplantation
|February 24, 2017
PubMed

Insights

Mechanistic target of rapamycin (mTOR) inhibitors combat atherosclerosis by reducing plaque and boosting cholesterol removal. However, they cause dyslipidemia, necessitating cholesterol-lowering drugs for effective management.

Area of Science:

  • Cardiovascular Science
  • Pharmacology

Background:

  • Mechanistic target of rapamycin (mTOR) inhibitors demonstrate antiatherosclerotic properties.
  • Key effects include plaque macrophage depletion, autophagy induction, and enhanced cholesterol efflux.
  • Dyslipidemia is a significant side effect, posing a risk for atherosclerosis.

Purpose of the Study:

  • To analyze the dual effects of mTOR inhibitors on atherosclerosis and lipid metabolism.
  • To evaluate the clinical implications of mTOR inhibitor-induced dyslipidemia.

Main Methods:

  • Review of existing literature on mTOR inhibitors and their impact on atherosclerotic plaques.
  • Analysis of metabolic pathways affected by mTOR inhibition, focusing on lipid handling.
  • Assessment of clinical guidelines for managing dyslipidemia in patients on mTOR inhibitors.

Main Results:

  • mTOR inhibitors reduce atherosclerotic burden through macrophage depletion and autophagy.
  • These agents paradoxically increase low-density lipoprotein cholesterol and activate lipolysis, leading to dyslipidemia.
  • Despite favorable antiatherosclerotic actions, the pro-dyslipidemic effect is a significant concern.

Conclusions:

  • mTOR inhibitors possess unique antiatherosclerotic benefits.
  • Management of treatment-induced dyslipidemia is crucial for patient safety.
  • Co-administration with cholesterol-lowering drugs is the recommended strategy for managing dyslipidemia.

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