JACC: Basic to Translational Science (Apr 2016)

A Myocardial Slice Culture Model Reveals Alpha-1A-Adrenergic Receptor Signaling in the Human Heart

  • R. Croft Thomas, Jr., MD,
  • Abhishek Singh, MD, PhD,
  • Patrick M. Cowley, PhD,
  • Bat-Erdene Myagmar, MD, PhD,
  • Megan D. Montgomery, PhD,
  • Philip M. Swigart, BS,
  • Teresa De Marco, MD,
  • Anthony J. Baker, PhD,
  • Paul C. Simpson, MD

DOI
https://doi.org/10.1016/j.jacbts.2016.03.005
Journal volume & issue
Vol. 1, no. 3
pp. 155 – 167

Abstract

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The authors used 52 nonfailing and failing human hearts to develop a simple, high throughput left ventricular myocardial slice model that is stable by ATP and viability assays for at least 3 days. The model supports studies of signaling, contraction, and viral transduction. They use the model to show for the first time that the alpha-1A-adrenergic receptor, which is present at very low abundance in the human myocardium, activates cardioprotective ERK with nanomolar EC50 in failing heart slices and stimulates a positive inotropic effect. This model should be useful for translational studies, to test whether molecules discovered in basic experiments are functional in the human heart.

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