Mast Cell Activation Promotes Myocardial Remodeling in Alcoholic Cardiomyopathy
10.11714/jsysu.med.YX20260025
- VernacularTitle:肥大细胞激活促进酒精性心肌病的心肌重构
- Author:
Qinglang LI
1
;
Dongmei XIE
2
;
Xiuren GAO
3
Author Information
1. Department of Cardiology， The Sixth Affiliated Hospital，Sun Yat-sen University// Biomedical Innovation Center， The Sixth Affiliated Hospital， Sun Yat-sen University//NHC Key Laboratory of Assisted Circulation ［Sun Yat-sen University］，Guangzhou 510655， China
2. Department of Cardiology， The Third Affiliated Hospital； Sun Yat-sen University，Guangzhou 510630， China
3. Department of Cardiology， The First Affiliated Hospital；Sun Yat-sen University， Guangzhou 510080， China
- Publication Type:Journal Article
- Keywords:
mast cell;
alcoholic cardiomyopathy;
cardiac remodeling;
chymase;
apoptosis
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2026;47(3):451-458
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the role and related mechanisms of mast cells （MCs） in alcoholic cardiomyopathy （ACM）. MethodsAn ACM model was established in C57BL/6 mice by feeding them with alcohol liquid diet， and some model mice were intervened with cromolyn sodium， a mast cell stabilizer. Cardiac function， myocardial remodeling and the expression of related proteins were evaluated by echocardiography， tissue staining and Western blot. In vitro， neonatal rat ventricular cardiomyocytes （NRVCs） were stimulated with mast cell granules （MCGs） and/or alcohol， and pathway inhibitors were used to explore the underlying mechanisms. ResultsLong-term alcohol feeding caused significant cardiac dysfunction and mast cells activation in mice， accompanied by increased expressions of chymase， NOX2， NOX4 and apoptosis-related protein cleaved Caspase-3 （c-Caspase3） in myocardial tissues （P＜0.05）. Pretreatment with cromolyn sodium improved cardiac function， inhibited mast cell activation， and reduced the expressions of the above proteins. In vitro experiments showed that treatment with MCGs or alcohol alone up-regulated the expressions of c-Caspase3， NOX2， NOX4 and phosphorylated PKCβ1 （p-PKCβ1） in cardiomyocytes， and the combined stimulation of the two had a synergistic effect. Protease-activated receptor 2 （PAR2） inhibitor down-regulated the MCG-induced expressions of the above proteins. PKCβ1 inhibitor also inhibited the MCG-induced expressions of c-Caspase3， NOX2 and NOX4. Chymase inhibitor exerted a partial inhibitory effect on MCG-induced cardiomyocyte apoptosis. ConclusionDuring the development of ACM， mast cells are activated， and the released MCGs may promote cardiomyocyte apoptosis through the PAR2-PKCβ1-NOX2/NOX4 signaling pathway， in which chymase plays an important role.
