ANGPTL4 suppresses the profibrogenic functions of atrial fibroblasts induced by angiotensin II by up-regulating PPAR?

Objective(s): The present study's objective was to investigate the association between angiopoietin-like 4 (ANGPTL4) levels and the prognosis of Atrial fibrillation (AF), the causative effect in angiotensin II-(Ang II) induced AF, and its underlying mechanisms. Materials and Methods: Baseline serum ANGPTL-4 concentrations were measured in 130 patients with AF. Rat atrial fibroblasts were isolated from 14-day-old SD rats and transfected with Ang II treatment. Transfected cells were divided into: The control group, ANGPTL4-OE group, Ang II group, and Ang II+ANGPTL4-OE group. Transfected cells were used to analyze fibroblasts' proliferation, migration, and collagen production at the cellular level. RT-qPCR and western blotting evaluated the ANGPTL4-targeted gene and PPAR gamma-Akt pathway. Results: In patients with AF, serum ANGPTL4 concentrations decreased significantly compared with the healthy group. ANGPTL4 mRNA and protein expressions were significantly down-regulated in Ang II-induced cardiac fibroblasts. ANGPTL4 overexpression potentially attenuated Ang II-induced fibroblast proliferation, migration, and collagen production in atrial tissue. ANGPTL4 inhibited the signaling proteins, such as PPAR gamma, alpha-SMA, and Akt. Conclusion: Our experimental data speculate that ANGPTL4 is a key factor in regulating AF progression. Therefore, increasing ANGPTL4 expression could be an effective strategy for AF treatment.