Chemogenetic activation of intracardiac cholinergic neurons improves cardiac function in pressure overload-induced heart failure

Author:

Dyavanapalli Jhansi1,Hora Aloysius James1,Escobar Joan B.1,Schloen John2ORCID,Dwyer Mary Kate2,Rodriguez Jeannette2ORCID,Spurney Christopher F.3,Kay Matthew W.2ORCID,Mendelowitz David1

Affiliation:

1. Department of Pharmacology and Physiology, George Washington University, Washington, District of Columbia

2. Department of Biomedical Engineering, George Washington University, Washington, District of Columbia

3. Children’s National Heart Institute, Center for Genetic Medicine Research, Children’s National Health System, Washington, District of Columbia

Abstract

Intracardiac ganglia form the final common pathway for the parasympathetic innervation of the heart. This study has used a novel chemogenetic approach within transgenic ChAT-Cre rats [expressing only Cre-recombinase in choline acetyl transferase (ChAT) neurons] to selectively increase intracardiac cholinergic parasympathetic activity to the heart in a pressure overload-induced heart failure model. The findings from this study confirm that selective activation of intracardiac cholinergic neurons lessens cardiac dysfunction and mortality seen in heart failure, identifying a novel downstream cardiac-selective target for increasing cardioprotective parasympathetic activity in heart failure.

Funder

National Institutes of Health

American Autonomic Postdoctoral Fellowship

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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