The protective effect of gamma aminobutyric acid B receptor activation on sympathetic nerve remodeling via the regulation of M2 macrophage polarization after myocardial infarction.
Rev Port Cardiol
; 42(2): 125-135, 2023 02.
Article
em En, Pt
| MEDLINE
| ID: mdl-36759072
ABSTRACT
INTRODUCTION & OBJECTIVES:
Acute myocardial infarction (AMI) in coronary heart disease is a leading cause of sudden death primarily due to malignant ventricular arrhythmias (VAs). Inflammatory cell infiltration and inflammation-induced overactivation of sympathetic nerves are the major cause of VAs in AMI pathophysiological processes. Type 2 macrophages play an anti-inflammatory role in AMI. Targeting macrophages may be a therapeutic strategy to prevent VAs post AMI. We found that gamma aminobutyric acid (GABA) promotes macrophages polarized to M2 and hypothesized that GABA might exert anti-inflammatory effects by promoting type 2 macrophage polarization in AMI. We aim to characterized GABAB receptor distribution, function, and mechanisms in M2 macrophage polarization and explored the functional aspect of GABAB receptor activation in sympathetic remodeling.RESULTS:
Gamma aminobutyric acid B receptors were expressed on macrophage surface both in vitro and in vivo. GABAB receptor agonist baclofen, GABA promoted macrophage switch to M2. While GABAB receptor antagonist CGP52432 blocked a baclofen induced switch to M2 polarization. GABA and baclofen increased M2 macrophage percentage and CGP52432 blocked this process in vivo. Also, IL-10 and TGF-ß1 released by M2 were increased in both AMI and baclofen/AMI group; Serum NE levels were decreased by baclofen. All the above effects were reversed by CGP52432 treatment. Baclofen decreased TH and GAP-43 staining while CGP52432 enhanced their expression post AMI indicating GABAB receptor activation inhibited sympathetic nerve sprouting and activity by reducing NE release.CONCLUSIONS:
Gamma aminobutyric acid B receptor activation promoted M2 polarization and protested AMI heart by regulating sympathetic nerve remodeling.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de GABA
/
Infarto do Miocárdio
Limite:
Humans
Idioma:
En
/
Pt
Revista:
Rev Port Cardiol
Assunto da revista:
CARDIOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China