Comprehensive and translational analysis of cardioprotective signal transduction in response to conditioning

• Applicant: Professor Dr. Gerd Heusch
• Subject Area: Anatomy and Physiology ; Cardiology, Angiology
• Term: from 2009 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 140575950

• Final Report Year: 2018

Final Report Abstract

The project addressed the signal transduction of cardioprotection, more specifically that by remote ischemic conditioning, i.e. brief ischemia/reperfusion cycles at a peripheral limb which induces protection from sustained myocardial ischemia/reperfusion and reduces infarct size in an anesthetized pig model. Such protection was induced by peripheral ischemia/reperfusion before (preconditioning) or during (perconditioning) coronary occlusion and mediated by a signal transduction of peripheral sensory nerve activation, efferent vagal nerve activation, release of cardioprotective mediators into the blood (notably from the spleen) and activation of myocardial STAT 3. Humoral mediators of cardioprotection were also identified in healthy volunteers. Importantly, cardioprotection by remote ischemic conditioning was successfully translated to patients undergoing coronary artery bypass surgery, as they had reduced troponin release, less post-operative complications and better survival.

Publications

• Across-species transfer of protection by remote ischemic preconditioning with species-specific myocardial signal transduction by reperfusion injury salvage kinase and survival activating factor enhancement pathways. Circ Res 117: 279-288 (2015)
  Skyschally A., Gent S., Amanakis G., Schulte C., Kleinbongard P., Heusch G.
  (See online at https://doi.org/10.1161/CIRCRESAHA.117.306878)
• Kinetics and speciai activation properties of circuiating factor(s) from healthy volunteers undergoing remote ischemic preconditioning. JACC Basic Transl Sci 1:3-13 (2016)
  Hildebrandt HA, Kreienkamp V, Gent S, Kahlert P, Heusch G, Kleinbongard P
  (See online at https://doi.org/10.1016/j.jacbts.2016.01.007)
• Ischemic preconditioning in pigs: a causal role for signal transducer and activation of transcription 3. Am J Physiol Heart Circ Physiol 312: H478-H484 (2017)
  Gent S, Skyschally A, Kleinbongard P, Heusch G
  (See online at https://doi.org/10.1152/ajpheart.00749.2016)
• Proteomics/phosphoproteomics of left ventricular biopsies from patients with surgical coronary revascularization and pigs with coronary occlusion/reperfusion: remote ischemic preconditioning. Sci Rep 7, 7629 (2017)
  Gedik N, Krüger M, Thielmann M, Kottenberg E, Skyschally A, Frey UH, Carlo E, Peters J, Jakob H, Heusch G, Kleinbongard P
  (See online at https://doi.org/10.1038/s41598-017-07883-5)
• STAT3 as a common signal of ischemic conditioning - a lesson on “rigor and reproducibility” in precilnical studies on cardioprotection. Basic Res Cardiol 113:3 (2018)
  Kleinbongard P, Skyschaliy A, Gent S, Pesch M, Heusch G
  (See online at https://doi.org/10.1007/s00395-017-0660-z)