An innovative sequence of hypoxia-reoxygenation on adult mouse cardiomyocytes in suspension to perform multilabeling analysis by flow cytometry

Am J Physiol Cell Physiol. 2020 Feb 1;318(2):C439-C447. doi: 10.1152/ajpcell.00393.2019. Epub 2019 Dec 25.

Abstract

Cardiovascular diseases remain the leading cause of death worldwide. Although major therapeutic progress has been made during the past decades, a better understanding of the underlying mechanisms will certainly help to improve patient's prognosis. In vitro models, particularly adult mouse cardiomyocytes, have been largely used; however, their fragility and large size are major obstacles to the use of flow cytometry. Conventional techniques, such as cell imaging, require the use of large numbers of animals and are time consuming. Here, we described a new, simple, and rapid one-day protocol using living adult mouse cardiomyocytes in suspension exposed to hypoxia-reoxygenation that allows a multilabeling analysis by flow cytometry. Several parameters can be measured by fluorescent probes labeling to assess cell viability (propidium iodide, calcein-AM, and Sytox Green), mitochondrial membrane potential [DilC1(5) and TMRM], reactive oxygen species production (MitoSOX Red), and mitochondrial mass (MitoTracker Deep Red). We address the robustness and sensitivity of our model using a cardioprotective agent, cyclosporine A. Overall, our new experimental set-up offers a high-speed quantitative multilabeling analysis of adult mouse cardiomyocytes exposed to hypoxia-reoxygenation. Our model might be interesting to investigate other cellular stresses (oxidative and inflammation) or to perform pharmacological screening.

Keywords: cardiomyocytes; flow cytometry; myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiotonic Agents / pharmacology
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / physiology*
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Flow Cytometry / methods
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / physiology
  • Myocardial Reperfusion Injury / drug therapy
  • Myocardial Reperfusion Injury / immunology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / physiology*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Oxygen / metabolism*
  • Reactive Oxygen Species / metabolism

Substances

  • Cardiotonic Agents
  • Reactive Oxygen Species
  • Oxygen