Key result
Cardiac TGF-β1 overexpression increases pacing-induced AF duration ~6-fold compared with wild-type controls.
Why the study?
Atrial fibrosis mediated by the pro-fibrotic molecule TGF-β1 plays a primary role in AF, prompting investigation into whether cardiac TGF-β1 overexpression modulates AF susceptibility and related gene expression in a transgenic goat model.
Does cardiac-specific TGF-β1 overexpression increase atrial fibrosis, alter molecular remodeling, and increase atrial fibrillation inducibility without increasing inflammation in a transgenic female goat model compared to wild-type controls?
Does cardiac-specific TGF-β1 overexpression increase atrial fibrosis, alter molecular remodeling, and increase atrial fibrillation inducibility without increasing inflammation in a transgenic female goat model compared to wild-type controls?
This large-animal transgenic model demonstrates that TGF-β1-driven atrial fibrosis and extracellular matrix remodeling are sufficient to significantly increase atrial fibrillation susceptibility and duration independently of tissue inflammation.
Answers are grounded in this paper and cite their sources.
TGF-β1-driven fibrosis may increase AF susceptibility without inflammation in goats; leaves open relevance to human AF mechanisms and therapies.
Atrial Fibrillation (AF) is the most common cardiac arrhythmia in adult humans. Atrial fibrosis plays a primary role in developing and sustaining this disease phenotype. Specifically, TGF-β1, a potent pro-fibrotic molecule, is implicated in cell turnover, increasing the amount of extracellular matrix in the heart. This increase leads to aberrant electrical signaling and can produce AF. In this study, we hypothesized that TGF-β1 modulates AF susceptibility in TGF-β1 transgenic goats and that genes related to TGF-β1 and AF would be differentially expressed when compared to wild-type (WT) controls. Transgenic (TG) female goats expressing the active form of human TGF-β1 in an atrial-specific manner and age-matched wild-type female goats were utilized in the study. Pacemakers were implanted in all animals for continuous arrhythmia monitoring and AF inducibility, which was evaluated using five separate 10s bursts of atrial pacing (200–160 ms). Tissue samples were collected from both atria of TG and WT goats. RNA was extracted, and gene expression analyses were run on a selected panel of genes. Immunohistochemistry was performed on atrial tissue to evaluate for the presence of selected inflammatory markers to elucidate AF substrate in these animals. There was a significant increase in AF inducibility in both frequency and duration in TGF-β1 goats compared to their WT counterparts. There was no significant difference in the number of inflammatory cells tested by immunohistochemistry. Differentially expressed genes between the TG and WT groups were found in several functional categories including AF, apoptosis, extracellular matrix, inflammation, and TGF-β1. These data support the hypothesis that fibrosis is an important modulator of AF susceptibility. More specifically, an overexpression of TGF-β1 significantly increases expression levels of ECM proteins and TGF-β1 signaling modulators, adding to elevated AF risk without altering underlying inflammation.
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Regouski et al. (2026) studied Atrial fibrosis and atrial fibrillation susceptibility (n=12). Cardiac-specific human TGF-β1 overexpression (transgenic model) with burst atrial pacing vs. Age- and sex-matched wild-type female goats undergoing identical burst atrial pacing was evaluated on Average duration of pacing-induced atrial fibrillation (AF) episodes (seconds) (p=0.04). Cardiac TGF-β1 overexpression in transgenic female goats significantly increased pacing-induced AF duration compared to wild-type controls (51.30 vs 8.98 s, p=0.04) without increasing immune cells.
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