Reduced apelin expression and atrial fibrosis in postoperative atrialfibrillation following coronary artery bypass grafting

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Postoperative atrial fibrillation (POAF) and atrial fibrosis following coronary artery bypass grafting (CABG) (n=18). Intervention: Postoperative atrial fibrillation (POAF) and reduced apelin expression (clinical exposure); exogenous apelin 10 nM or apelin siRNA knockdown in TGF-beta1-stimulated neonatal rat atrial fibroblasts (experimental) vs. CABG patients remaining in sinus rhythm without POAF (n=6) and congenital heart disease patients in sinus rhythm (n=6). Primary outcome: Atrial apelin expression, serum apelin concentration (postoperative day 2), atrial collagen deposition, and TGF-beta1/Smad2 signaling protein levels (p=<0.05).

Q: What does this research mean for the field?

CABG patients who develop postoperative atrial fibrillation exhibit lower atrial and serum apelin levels alongside increased atrial fibrosis and TGF-β1/Smad2 pathway activation, which apelin can functionally attenuate. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Yijun Xu; Zhi Chen; Peng Liu; Wen Wen; Xiaowei Li; Hao Wang

doi:10.17305/bb.2026.14946

November 6, 2026Biomolecules and BiomedicineOpen Access

Reduced apelin expression and atrial fibrosis in postoperative atrialfibrillation following coronary artery bypass grafting

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Key result

Reduced atrial and serum apelin levels were significantly associated with increased atrial collagen deposition and elevated TGF-beta1/Smad2 phosphorylation in patients developing POAF after CABG.

Why the study?

The role of apelin in atrial fibrosis linked to POAF following CABG and its impact on profibrotic signaling were not fully understood.

Is reduced apelin expression associated with atrial fibrosis and TGF-beta1/Smad2 signaling activation in patients who develop postoperative atrial fibrillation following coronary artery bypass grafting?

Key Points

Investigate the link between apelin expression, atrial fibrosis, and postoperative atrial fibrillation after coronary artery bypass grafting, and assess apelin's impact on profibrotic signaling.
Evaluated preoperative left atrial appendage tissue histology and postoperative day 2 serum apelin levels across 18 patients (six CABG with POAF, six CABG without POAF, and six congenital heart disease reference controls).
Stimulated primary neonatal rat atrial fibroblasts with TGF-β1 with or without apelin, and measured fibrosis-associated marker expression after apelin siRNA knockdown.
Compared with CABG patients without POAF, the CABG with POAF group exhibited lower atrial apelin expression, lower serum apelin concentrations, increased collagen deposition, elevated TGF-β1 expression, and enhanced Smad2 phosphorylation, with total Smad2 unchanged.
In cultured atrial fibroblasts, apelin attenuated TGF-β1-induced fibroblast activation, collagen expression, and Smad2 phosphorylation, whereas apelin silencing increased α-SMA, Collagen I, Collagen III, and TIMP-1 protein levels.

Study Design

Type

Observational (n=18)

Blinding

Histological and immunohistochemical analyses were quantified by two independent investigators blinded to group allocation

Multicenter

No

Structured PICO

Is reduced apelin expression associated with atrial fibrosis and TGF-beta1/Smad2 signaling activation in patients who develop postoperative atrial fibrillation following coronary artery bypass grafting?

P

Population

18 patients at a single center in China (6 off-pump CABG patients with postoperative atrial fibrillation, 6 CABG patients without POAF, and 6 congenital heart disease patients in sinus rhythm) without prior documented atrial fibrillation, monitored for 7 days postoperatively, alongside primary neonatal rat atrial fibroblast experiments.

E

Exposure

Clinical exposure: Development of postoperative atrial fibrillation (POAF, episode >5 min within 7 days post-CABG) and endogenous apelin expression. In vitro intervention: Pretreatment with 10 nM apelin for 20 min followed by 10 ng/mL TGF-beta1 for 48 h, or apelin gene silencing via siRNA.

C

Comparator

Clinical: Patients undergoing elective isolated off-pump CABG who remained in sinus rhythm without POAF (n=6), and patients with congenital heart disease in sinus rhythm (n=6). In vitro: Untreated control fibroblasts or TGF-beta1 stimulation without apelin.

O

Outcome

Atrial fibrosis (collagen deposition via Masson's trichrome staining; Collagen I, Collagen III, MMP-2, TIMP-1, and alpha-SMA expression), apelin expression in preoperative left atrial appendage tissue and postoperative day 2 serum, and TGF-beta1/Smad2 pathway activation (TGF-beta1, total Smad2, and phosphorylated Smad2).surrogate

Main Result

p-value: p=<0.05

This exploratory translational study identifies an association between reduced atrial and circulating apelin levels, enhanced TGF-beta1/Smad2 signaling, and pre-existing atrial fibrosis in patients developing POAF after off-pump CABG, while demonstrating in vitro that apelin attenuates TGF-beta1-induced fibroblast activation.

Limitations

Small clinical cohort (n=18) recruited from a single center, limiting statistical power, precision, and generalizability
Clinical analyses were unadjusted univariate comparisons and could not account for potential confounding factors
Congenital heart disease reference group was not clinically comparable to the CABG cohort
Serum samples were collected on postoperative day 2 while POAF could occur anywhere within 7 days, so timing relative to POAF onset was not established
Clinical associations do not establish a causal relationship between reduced apelin expression and atrial fibrosis
Primary atrial fibroblasts isolated from 1-2-day-old rats may not fully reproduce the phenotype of adult human atrial fibroblasts
Small clinical sample size (n=18 total, n=6 per group) from a single center, limiting statistical power and generalizability
Unadjusted univariate clinical analyses without multivariable adjustment for potential confounders
Uncertain temporal relationship between postoperative day 2 serum sampling and POAF onset within the 7-day window
Observational clinical associations cannot establish causality between apelin deficiency and atrial remodeling
In vitro model used neonatal (1-2-day-old) rat atrial fibroblasts rather than adult human atrial fibroblasts

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Implication

Apelin assessment should not yet guide POAF risk stratification after CABG; leaves open whether apelin supplementation attenuates TGF-β1/Smad2-driven atrial fibrosis.

Abstract

The role of apelin in atrial fibrosis linked to postoperative atrial fibrillation (POAF) following coronary artery bypass grafting (CABG) is not fully understood. This exploratory study investigated apelin's association with POAF-related atrial fibrosis and its impact on profibrotic signaling. The study included 18 patients: six CABG patients with POAF, six CABG patients without POAF, and six patients with congenital heart disease in sinus rhythm (serving as a secondary reference). Left atrial appendage tissue was analyzed histologically and molecularly, and serum apelin levels were measured on postoperative day 2 in CABG patients. Primary neonatal rat atrial fibroblasts were treated with transforming growth factor-β1 (TGF-β1) both with and without apelin, or subjected to apelin silencing. Compared with CABG patients without POAF, the POAF group exhibited lower atrial apelin expression and serum concentrations, increased collagen deposition, elevated TGF-β1 expression, and enhanced phosphorylation of mothers against decapentaplegic homolog 2 (Smad2), while total Smad2 remained unchanged. Experimentally, apelin attenuated TGF-β1-induced fibroblast activation, collagen expression, and Smad2 phosphorylation. Conversely, apelin silencing increased the expression of fibrosis-associated proteins. These preliminary findings suggest a link between reduced apelin and atrial fibrosis, as well as POAF after CABG. They also indicate antifibrotic effects of apelin, potentially mediated through TGF-β1/Smad2 signaling. Further research with larger clinical cohorts and complementary experimental models is necessary to fully elucidate the pathway mediation and clinical significance of these findings.

Discussion

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Cite This Study

Xu et al. (2026) conducted an observational in Postoperative atrial fibrillation (POAF) and atrial fibrosis following coronary artery bypass grafting (CABG) (n=18). Postoperative atrial fibrillation (POAF) and reduced apelin expression (clinical exposure); exogenous apelin 10 nM or apelin siRNA knockdown in TGF-beta1-stimulated neonatal rat atrial fibroblasts (experimental) vs. CABG patients remaining in sinus rhythm without POAF (n=6) and congenital heart disease patients in sinus rhythm (n=6) was evaluated on Atrial apelin expression, serum apelin concentration (postoperative day 2), atrial collagen deposition, and TGF-beta1/Smad2 signaling protein levels (p=<0.05). Reduced atrial and serum apelin levels were significantly associated with increased atrial collagen deposition and elevated TGF-beta1/Smad2 phosphorylation in patients developing POAF after CABG.

synapsesocial.com/papers/6aefbd4950d2071ffda4bbca https://doi.org/10.17305/bb.2026.14946

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Reduced apelin expression and atrial fibrosis in postoperative atrialfibrillation following coronary artery bypass grafting

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Reduced apelin expression and atrial fibrosis in postoperative atrialfibrillation following coronary artery bypass grafting

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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