What is the clinical evidence from this study?

Study design: Other. Population: Chronic atrial fibrillation (n=72). Intervention: Chronic atrial fibrillation vs. Sinus rhythm. Primary outcome: Degree of atrial fibrosis and expression of PDGF-B, PDGFR-β, and collagen type I.

January 1, 2016

The Role of Platelet-Derived Growth Factor-B/Platelet-Derived Growth Factor Receptor-β Signaling in Chronic Atrial Fibrillation

Key Result

Chronic atrial fibrillation was associated with significantly increased atrial fibrosis and expression of PDGF-B, PDGFR-β, and collagen type I compared to sinus rhythm.

Structured PICO

Does PDGF-B/PDGFR-β signaling contribute to atrial fibrosis in chronic atrial fibrillation?

Population

72 patients (39 with chronic atrial fibrillation and 33 with sinus rhythm) evaluated for atrial fibrosis and gene expression, alongside canine and rat models.

Exposure

In vitro treatment with PDGF-BB or PDGF-BB + PDGFR inhibitor AG1295; rapid atrial pacing in canines.

Comparator

Sinus rhythm (in humans); control and sham groups (in canines); PDGF-BB alone (in vitro).

Outcome

Degree of atrial fibrosis and gene/protein expression of PDGF-B, PDGFR-β, and collagen type I (COL1).surrogate

PDGF-B/PDGFR-β signaling promotes atrial fibroblast proliferation and collagen secretion, driving atrial fibrosis in AF and highlighting a potential therapeutic target.

Abstract

OBJECTIVE: To explore the role of platelet-derived growth factor-B (PDGF-B)/platelet-derived growth factor receptor-β (PDGFR-β) signaling in chronic atrial fibrillation (AF). METHODS: Thirty-nine AF patients and 33 patients with sinus rhythm (SR) were enrolled. Twenty canines were randomized into 5 groups: control, sham and AF lasting 1, 2 or 4 weeks. The AF canine models were made by rapid atrial pacing. Rat atrial fibroblasts were treated with PDGF-BB or PDGF-BB + PDGFR inhibitor AG1295, respectively. Gene expression in the right atrial appendage of patients, the left atrium of canines and rat atrial fibroblasts was measured by quantitative real-time PCR and Western blot, respectively. The degree of atrial fibrosis was evaluated by Masson trichrome staining. RESULTS: The degree of atrial fibrosis and the expression of PDGF-B, PDGFR-β and collagen type I (COL1) in AF patients significantly increased compared to patients with SR. The degree of atrial fibrosis and the expression of PDGF-B and COL1 in canines increased progressively with the increased duration of AF. The expression of PDGFR-β increased progressively 2 weeks after AF. PDGF-BB promoted the proliferation and COL1 secretion of rat atrial fibroblasts. AG1295 attenuated these effects. CONCLUSIONS: Our study suggests that PDGF-B/PDGFR-β signaling, which promotes the proliferation and COL1 secretion of atrial fibroblasts, is an important contributor to atrial fibrosis in AF and may represent a novel target for the intervention of AF.

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