Hypothesis Article: Exosomal miR-210-3p derived from atrial myocytes as a novel mechanism contribute to cardiac fibrosis in atrial fibrillation

Cardiac fibrosis plays a critical role in the development of atrial fibrillation (AF). However, the pathogenesis of atrial fibrosis remains unclear. Recent studies suggest that exosomes mediated cellular crosstalk leads to diverse cardiovascular diseases. The aim of our study is to investigate the role of exosomal miR-210-3p derived from atrial myocytes in promoting the proliferation and differentiation of atrial fibroblasts and resulting in atrial fibrosis during AF. miRNAs sequencing analysis revealed that miR-210-3p expression significantly increased in exosomes of tachypacing atrial myocytes, and serum of AF patients. In vitro, miR-210-3p inhibitor reversed tachypacing-induced proliferation and collagen synthesis of atrial fibroblasts. miR-210-3p KO could reduce the inducibility of AF and ameliorate atrial fibrosis induced by Ang Ⅱ. mRNA sequencing and dual-luciferase reporter assay proved that glycerol-3-phosphate dehydrogenase 1-like (GPD1L) is the potential target gene of miR-210-3p. GPD1L regulated atrial fibrosis via PI3K/AKT signaling pathway in vivo and in vitro. Besides, si-GPD1L intensified atrial fibroblasts proliferation and these effects could be reversed by PI3K inhibitor (LY294002). We demonstrate that atrial myocytes derived exosomal miR-210-3p promoted the proliferation and collagen synthesis via inhibiting GPD1L in atrial fibroblasts. Preventing pathological crosstalk between atrial myocytes and fibroblasts may as a novel target to improve atrial fibrosis in AF.