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

Joseph J. Sepe, PhD; Ryan T. Gardner, PhD; Matthew R. Blake, BS; Deja M. Brooks, BS; Melanie A. Staffenson, BS; Courtney B. Betts, PhD; Sam Sivagnanam, MS; William Larson, BS; Sushil Kumar, PhD; Richard G. Bayles, PhD; Haihong Jin, PhD; Michael S. Cohen, PhD; Lisa M. Coussens, PhD; Beth A. Habecker, PhD

JACC: Basic to Translational Science (Sep 2022)

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

Joseph J. Sepe, PhD,
Ryan T. Gardner, PhD,
Matthew R. Blake, BS,
Deja M. Brooks, BS,
Melanie A. Staffenson, BS,
Courtney B. Betts, PhD,
Sam Sivagnanam, MS,
William Larson, BS,
Sushil Kumar, PhD,
Richard G. Bayles, PhD,
Haihong Jin, PhD,
Michael S. Cohen, PhD,
Lisa M. Coussens, PhD,
Beth A. Habecker, PhD

Affiliations

Joseph J. Sepe, PhD: Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon, USA; Department of Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA
Ryan T. Gardner, PhD: Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon, USA; Department of Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA
Matthew R. Blake, BS: Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon, USA
Deja M. Brooks, BS: Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon, USA
Melanie A. Staffenson, BS: Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon, USA
Courtney B. Betts, PhD: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA
Sam Sivagnanam, MS: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA
William Larson, BS: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA
Sushil Kumar, PhD: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA
Richard G. Bayles, PhD: Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon, USA
Haihong Jin, PhD: Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon, USA
Michael S. Cohen, PhD: Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon, USA
Lisa M. Coussens, PhD: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA
Beth A. Habecker, PhD: Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon, USA; Department of Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA; Address for correspondence: Dr Beth A. Habecker, Department of Chemical Physiology and Biochemistry, L334, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.

Journal volume & issue: Vol. 7, no. 9
pp. 915 – 930

Abstract

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Summary: 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.

Published in JACC: Basic to Translational Science

ISSN: 2452-302X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.journals.elsevier.com/jacc-basic-to-translational-science/

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