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