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Cardiomodulatory Effects of Cardiometabolic and Antihyperglycemic Medications: The Roles of Oxidative and Endoplasmic

Arshag D Mooradian1

  • 1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida Jacksonville College of Medicine, 653-1 West 8th Street, Jacksonville, FL, 32209, USA. arshag.mooradian@jax.ufl.edu.

American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions
|October 11, 2024
PubMed

Insights

Diabetes complications like hyperglycemia and hypoglycemia cause cellular stress, increasing cardiovascular risk. New diabetes drugs may protect the heart by reducing this stress.

Area of Science:

  • Cardiology
  • Endocrinology
  • Cellular Biology

Background:

  • Uncontrolled diabetes, marked by hyperglycemia and hypoglycemia, elevates cardiovascular disease (CVD) risk.
  • Both high and low blood sugar levels induce cellular stress, particularly endoplasmic reticulum (ER) stress, a known CVD promoter.

Purpose of the Study:

  • To review the role of cellular stress reduction in the cardioprotective effects of modern diabetes medications.
  • To explore the hypothesis that cellular stress is a key factor in cardiovascular disease.

Main Methods:

  • Literature review focusing on the mechanisms of action of contemporary anti-hyperglycemic drugs and other cardioprotective agents.
  • Analysis of studies investigating the impact of hyperglycemia, hypoglycemia, and pharmacological interventions on cellular stress pathways (oxidative and ER stress).

Main Results:

  • Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT-2) inhibitors reduce both oxidative and ER stress in human coronary artery endothelial cells.
  • Cardioprotective drugs like statins and renin-angiotensin-aldosterone system (RAAS) inhibitors also exhibit cellular stress-reducing effects.
  • Antioxidants may worsen ER stress, potentially explaining unfavorable clinical trial outcomes.

Conclusions:

  • Cellular stress reduction is a potential mechanism underlying the cardioprotective benefits of contemporary diabetes drugs.
  • Further clinical trials are warranted to confirm the central role of cellular stress in cardiovascular disease pathogenesis and management.

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