Prostaglandin G/H synthase 1 promotes thrombosis in atrial fibrillation through modulation of platelet activation, macrophage infiltration, inflammation, and autophagy inhibition.

Abstract

Background: Prostaglandin G/H synthase 1 (PTGS1) is known to regulate platelet function and inflammation. However, its role in atrial fibrillation (AF)-related thrombosis is not well understood. This study investigates the role of PTGS1 in AF-associated thrombus formation and its underlying mechanisms.

Methods: Left atrial appendage (LAA) tissues were collected from 48 patients undergoing valve replacement surgery, divided into three groups: sinus rhythm (SR), AF with thrombus [AF (+) T (+)], and AF without thrombus [AF (+) T (-)]. PTGS1 expression, platelet activation markers (MPA, sCD40L, and d-dimer), macrophage phenotypes (M1 and M2), inflammatory cytokines (IL-1β, TNF-α, IL-6), and autophagy-related proteins (LC3II and p62) were assessed. Furthermore, the effect of PTGS1 manipulation on autophagy in endocardial endothelial cells (EECs) was examined using cell transfection experiments.

Results: PTGS1 expression was significantly higher in LAA tissues of AF (+) T (+) patients compared to AF (+) T (-) and SR groups. It was positively correlated with reduced LAA emptying velocity (LAAEV), higher CHA2DS2-VASc scores, and elevated platelet activation markers (MPA, sCD40L, and d-dimer). Data also showed increased M1 macrophage infiltration and higher pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) in AF (+) T (+) patients, with PTGS1 expression strongly linked to these markers. Furthermore, PTGS1 overexpression inhibited autophagy in EECs by decreasing LC3II/LC3I ratio and increasing p62 levels, while PTGS1 knockdown promoted autophagy, protecting against endothelial dysfunction.

Conclusions: PTGS1 is overexpressed in AF patients with thrombosis and may play an important role in promoting thrombus formation through enhanced platelet activation, inflammation, and inhibition of autophagy.