Galanin Regulates Myocardial Mitochondrial ROS Homeostasis and Hypertrophic Remodeling Through GalR2

Frederic Boal; Mathieu Cinato; Andrei Timotin; Heike Münzberg; Emily Qualls-Creekmore; Solomiia Kramar; Halyna Loi; Jerome Roncalli; Sokhna Keita; Helene Tronchere; Oksana Kunduzova

doi:10.3389/fphar.2022.869179

Galanin Regulates Myocardial Mitochondrial ROS Homeostasis and Hypertrophic Remodeling Through GalR2

Front Pharmacol. 2022 Mar 31:13:869179. doi: 10.3389/fphar.2022.869179. eCollection 2022.

Authors

Frederic Boal^{1

2}, Mathieu Cinato^{1

2}, Andrei Timotin^{1

2}, Heike Münzberg³, Emily Qualls-Creekmore³, Solomiia Kramar^{1

2}, Halyna Loi^{1

2}, Jerome Roncalli^{1

2

4}, Sokhna Keita^{1

2}, Helene Tronchere^{1

2}, Oksana Kunduzova^{1

2}

Affiliations

¹ National Institute of Health and Medical Research (INSERM) U1297, Toulouse, France.
² Paul Sabatier University, Toulouse, France.
³ Neurobiology of Nutrition and Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, CA, United States.
⁴ Department of Cardiology, Toulouse University Hospital, Toulouse, France.

Abstract

The regulatory peptide galanin is broadly distributed in the central nervous systems and peripheral tissues where it modulates numerous physiological and pathological processes through binding to its three G-protein-coupled receptors, GalR1-3. However, the function and identity of the galaninergic system in the heart remain unclear. Therefore, we investigated the expression of the galanin receptors in cardiac cells and tissues and found that GalR2 is the dominant receptor subtype in adult mouse hearts, cardiomyocytes and H9C2 cardiomyoblasts. In vivo, genetic suppression of GalR2 promotes cardiac hypertrophy, fibrosis and mitochondrial oxidative stress in the heart. In vitro, GalR2 silencing by siRNA abolished the beneficial effects of galanin on cell hypertrophy and mitochondrial reactive oxygen species (ROS) production. These findings unravel new insights into the role of galaninergic system in the heart and suggest novel therapeutic strategies in heart disease.

Keywords: cardiac remodeling; galanin; galanin receptors; hypertrophy; oxidative stress.