Renal denervation attenuates cardiac fibrosis and improves left ventricular function in rats with myocardial infarction

Abstract

Abstract The sympathetic nervous system (SNS) plays a critical role in regulating inflammatory responses after myocardial infarction (MI). We aimed to investigate whether modulation of the SNS through renal denervation (RDN) influences myocardial remodeling following MI. MI in rats was induced 2 days after bilateral RDN or Sham surgery. Cardiac MRI showed that left ventricular ejection fraction was significantly higher in RDN-treated MI rats compared to Sham-treated MI rats. RNA sequencing of left ventricular tissue revealed that RDN suppresses fibrosis and inflammation related pathways at the whole transcriptome level, with clear separation of the experimental groups. These findings were confirmed by histochemical, gene, and protein expression analyses, which found a significantly higher extent of fibrosis and CD206 expression in the MI rats compared to RDN-treated MI rats. To simulate SNS activity, PMA-differentiated THP-1 cells were incubated with the β-adrenoceptor agonist isoprenaline. This resulted in upregulation of profibrotic macrophage gene expression, which was not the case after co-stimulation with a β1-adrenoceptor antagonist. Modulation of the SNS through RDN mitigates left ventricular remodeling post-MI by reducing myocardial fibrosis and scar size. Heightened SNS activity promotes a profibrotic macrophage phenotype. These findings support investigation into the therapeutic potential of RDN for managing MI patients.