Renal denervation in experimental autoimmune myocarditis: association with cardiac function and changes in calcium...

Renal denervation (RDN) has emerged as a potential therapeutic strategy to modulate autonomic imbalance and attenuate inflammation in cardiovascular disease. However, the mechanisms underlying its cardioprotective effects remain incompletely understood. In this study, we evaluated the functional and molecular effects of RDN in a rabbit model of experimental autoimmune myocarditis (EAM). A total of twenty-four male New Zealand white rabbits were randomly assigned to four groups: control, EAM, EAM with RDN for 4 weeks (EAM-RDN4W), and EAM with RDN for 6 weeks (EAM-RDN6W). Echocardiographic assessment demonstrated that EAM induced marked systolic dysfunction, as reflected by a reduction in left ventricular ejection fraction (LVEF) (approximately 65% in CTRL vs. 36% in EAM), whereas RDN was associated with partial preservation of cardiac performance, with recovery of LVEF to ~ 52% at 6 weeks after RDN. Histological analysis and TUNEL staining showed that RDN was associated with attenuation of myocardial inflammatory infiltration and cardiomyocyte apoptosis. RDN also reduced sympathetic activation, as evidenced by reduced ChAT-positive area in cardiac tissue and decreased circulating catecholamine levels. At the molecular level, RDN was associated with a shift toward improved calcium-handling balance, characterized by downregulation of Cav1.2, NCX, and RyR and upregulation of SERCA2a and phosphorylated phospholamban (p-PLB). Furthermore, RDN was associated with reduced activation of the MAPK/ERK pathway, as evidenced by decreased phosphorylation of Raf, MEK, ERK, and CREB. Collectively, these findings indicate that RDN is associated with improved cardiac function in EAM and with mitigation of inflammation-related myocardial injury, in parallel with coordinated changes in neurohumoral activity, calcium signaling, and MAPK/ERK pathway activation.