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S100B: a multifunctional role in cardiovascular pathophysiology

James N Tsoporis1, Forough Mohammadzadeh, Thomas G Parker

  • 1Division of Cardiology, Department of Medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, 30 Bond St., Toronto, ON, Canada.

Amino Acids
|March 6, 2010
PubMed

Insights

S100B protein, involved in cardiac hypertrophy and vascular disease, plays a dual role. While it inhibits cardiac hypertrophy and smooth muscle proliferation, it also increases apoptosis, making it a potential therapeutic target.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Cellular Signaling

Background:

  • S100B is a calcium-binding protein with intracellular and extracellular functions.
  • S100B expression is upregulated in the heart after myocardial infarction in humans and rats.

Purpose of the Study:

  • To investigate the role of S100B in cardiac hypertrophy and apoptosis following myocardial infarction.
  • To explore the therapeutic potential of targeting S100B in cardiovascular diseases.

Main Methods:

  • Overexpression and knockout of S100B in neonatal rat myocytes and transgenic mice.
  • Assessment of cardiac function, hypertrophy, and apoptosis after myocardial infarction and adrenergic stimulation.
  • Investigated the extracellular mechanism of S100B-induced apoptosis via receptor for advanced glycation end products (RAGE) and downstream signaling (ERK1/2, p53).

Main Results:

  • Forced S100B expression inhibited cardiac hypertrophy and vascular smooth muscle proliferation but increased apoptosis.
  • S100B knockout augmented hypertrophy and decreased apoptosis, preserving cardiac function post-myocardial infarction.
  • Extracellular S100B interacts with RAGE, activating ERK1/2 and p53 signaling to induce apoptosis.

Conclusions:

  • S100B exhibits opposing effects on cardiac hypertrophy and apoptosis, highlighting its complex role in cardiovascular disease.
  • Targeting both intracellular and extracellular functions of S100B presents a promising therapeutic strategy for cardiac and vascular diseases.

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