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Isolation, Culture, and Functional Characterization of Adult Mouse Cardiomyoctyes
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Caffeine induces cardiomyocyte hypertrophy via p300 and CaMKII pathways

Liang Shi1, Hao Xu1, Jinhong Wei1

  • 1The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.

Chemico-Biological Interactions
|August 6, 2014
PubMed

Insights

Caffeine causes cardiomyocyte hypertrophy by altering intracellular calcium levels. This process involves the ryanodine receptor (RyR2) and activates signaling pathways leading to cardiac dysfunction.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Cell Physiology

Background:

  • Caffeine is known to trigger intracellular calcium release in cardiomyocytes.
  • While caffeine's link to cardiac arrhythmia is established, its precise effects on cardiac function and hypertrophy remain unclear.

Purpose of the Study:

  • To investigate the impact of caffeine on cardiomyocyte hypertrophy.
  • To elucidate the associated intracellular signaling pathways involved in caffeine-induced cardiac changes.

Main Methods:

  • Ventricular myocytes from neonatal Sprague-Dawley rats were incubated with caffeine.
  • Measurements included total protein content, cell surface area, beta-myosin heavy chain (β-MHC) expression, and intracellular calcium (Ca2+) dynamics.
  • The role of cardiac ryanodine receptor (RyR2), CaMKII, and p300 was assessed using specific inhibitors (KN93, curcumin).

Main Results:

  • Caffeine incubation led to increased cardiomyocyte size, protein content, and β-MHC expression.
  • Basal intracellular Ca2+ levels rose, while sarcoplasmic reticulum (SR) Ca2+ content and oscillation amplitude decreased.
  • Inhibition of RyR2, CaMKII (with KN93), or p300 (with curcumin) abolished caffeine-induced hypertrophy and restored physiological Ca2+ levels in SR.

Conclusions:

  • Caffeine induces cardiomyocyte hypertrophy via altered intracellular Ca2+ handling, specifically through SR Ca2+ release.
  • This process activates the CaMKII and p300 signaling cascade, leading to enhanced myocyte enhancer factor-2 (MEF2) expression.
  • Targeting RyR2, CaMKII, or p300 may offer therapeutic strategies for caffeine-induced cardiac dysfunction.

Keywords:
CaMKIICaffeineCalciumHypertrophyp300

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