Therapeutics That Promote Sympathetic Reinnervation Modulate the Inflammatory Response After Myocardial Infarction.

Myocardial infarction (MI) triggers an inflammatory response that transitions from pro-inflammatory to reparative over time. Restoring sympathetic nerves in the heart after MI prevents arrhythmias. This study investigated if reinnervation altered the immune response after MI. This study used quantitative multiplex immunohistochemistry to identify the immune cells present in the heart 2 weeks after ischemia-reperfusion. Two therapeutics stimulated reinnervation, preventing arrhythmias and shifting the immune response from inflammatory to reparative, with fewer pro-inflammatory macrophages and more regulatory T cells and reparative macrophages. Treatments did not alter macrophage phenotype in vitro, which suggested reinnervation contributed to the altered immune response.
Competing Interests: This work was supported by the OCTRI Biomedical Innovation Program, the OHSU Bioscience Innovation Program, the M.J. Murdock Charitable Trust and National Institutes of Health grant R01 HL093056. Dr Gardner was supported by the American Heart Association (19POST34460031) and the National Institutes of Health (NIH) (grant T32HL094294). Ms Brooks was supported by NIH (grants UL1GM118964). Dr Sepe was supported by NIH (grant T32HL094294). Dr Habecker was supported by NIH (R01 HL093056). Dr Coussens was supported by NIH (1U01 CA224012, U2C CA233280), the Susan G Komen Foundation, the Knight Cancer Institute, and the Brenden-Colson Center for Pancreatic Care at OHSU. Drs Habecker and Gardner are the co-inventors of technology (ISP) that was used in this research, and that OHSU has licensed to NervGen Pharma Corp. This potential conflict of interest has been reviewed and managed by OHSU. Dr Coussens has been a paid consultant for Cell Signaling Technologies; has received reagent and/or research support from Plexxikon Inc, Pharmacyclics, Inc, Acerta Pharma, LLC, Deciphera Pharmaceuticals, LLC, Genentech, Inc, Roche Glycart AG, Syndax Pharmaceuticals Inc, Innate Pharma, NanoString Technologies, and Cell Signaling Technologies; has been a member of the Scientific Advisory Boards of Syndax Pharmaceuticals, Carisma Therapeutics, Zymeworks, Inc, Verseau Therapeutics, Cytomix Therapeutics, Inc., Kineta Inc, Hibercell, Inc, Cell Signaling Technologies, Alkermes Inc, PDX Pharmaceuticals, Genenta Sciences, and Pio Therapeutics Py Ltd; has been a member of the Lustgarten Therapeutics Advisory working group; and has been a site lead for the AstraZeneca Partner of Choice Network. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(© 2022 The Authors.)