title: Lights on for HIF-1α: genetically enhanced mouse cardiomyocytes for heart tissue imaging.
abstract: OBJECTIVE
  The hypoxia inducible factor-1 (HIF-1) is a suitable marker for tissue oxygenation. We intended to develop cardiomyocytes (CMs) expressing the oxygen-dependent degradation domain of HIF-1α fused to the firefly luciferase (ODD-Luc) followed by proof-of-concept for its applicability in the assessment of heart muscle oxygenation.
  
  
  RESULTS
  We first generated embryonic stem cell (ESC) lines (ODD-Luc ESCs) from a Tg ROSA26 ODD-Luc/+ mouse. Subsequent CMs selection was facilitated by stable integration of an antibiotic resistance expressed under the control of the αMHC promoter. ODD-Luc ESCs showed a strong Luc-signal within 1 h of hypoxia (1% oxygen), which coincided with endogenous HIF-1α. Engineered heart muscle (EHM) constructed with ODD-Luc CMs confirmed the utility of the model to sense hypoxia, and monitor reoxygenation also in a multicellular heart muscle model. Pharmacologically induced inotropy/chronotropy under isoprenaline resulted in enhanced Luc-signal suggesting enhanced oxygen consumption, leading to notable myocardial hypoxia.
  
  
  CONCLUSIONS
  ODD-Luc-CMs can be used to monitor dynamic changes of cardiomyocyte oxygenation in living heart muscle samples. We provide proof-of-concept for pharmacologically induced myocardial interventions and envision applications of the developed model in drug screens and fundamental studies of ischemia/reperfusion injury.
authors.affiliation: Institute of Cardiovascular Physiology, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Amke R
authors.initials: AR
authors.lastname: Hesse
authors.forename: Elif
authors.initials: E
authors.lastname: Levent
authors.forename: Anke
authors.initials: A
authors.lastname: Zieseniss
authors.forename: Malte
authors.initials: M
authors.lastname: Tiburcy
authors.forename: Wolfram H
authors.initials: WH
authors.lastname: Zimmermann
authors.forename: Dörthe M
authors.initials: DM
authors.lastname: Katschinski
mesh_terms: D000818:Animals; D005818:Genetic Engineering; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit