Abstract
BACKGROUND:
Atrial tissue fibrosis is linked to inflammatory cells, yet is incompletely understood. A growing body of literatureassociates peripheral blood levels of the antifibrotic hormone BNP (B-type natriuretic peptide) with atrial fibrillation (AF). Weinvestigated the relationship between pro-fibrotic tissue M2 macrophage marker Cluster of Differentiation (CD)163+, atrialprocollagen expression, and BNP gene expression in patients with and without AF.
METHODS AND RESULTS: In a cross-sectional study design, right atrial tissue was procured from 37 consecutive, consenting,stable patients without heart failure or left ventricular systolic dysfunction, of whom 10 had AF and 27 were non-AF controls.Samples were analyzed for BNP and fibro-inflammatory gene expression, as well as fibrosis and CD163+. Primary analysesshowed strong correlations (all P<0.008) between M2 macrophage CD163+ staining, procollagen gene expression, and myocardial BNP gene expression across the entire cohort. In secondary analyses without multiplicity adjustments, AF patients hadgreater left atrial volume index, more valve disease, higher serum BNP, and altered collagen turnover markers versus controls(all P<0.05). AF patients also showed higher atrial tissue M2 macrophage CD163+, collagen volume fraction, gene expressionof procollagen 1 and 3, as well as reduced expression of the BNP clearance receptor NPRC (all P<0.05). Atrial procollagen 3gene expression was correlated with fibrosis and BNP gene expression was correlated with serum BNP.
CONCLUSIONS: Elevated atrial tissue pro-fibrotic M2 macrophage CD163+ is associated with increased myocardial gene expression of procollagen and anti-fibrotic BNP and is higher in patients with AF. More work on modulation of BNP signaling fortreatment and prevention of AF may be warranted.
Atrial tissue fibrosis is linked to inflammatory cells, yet is incompletely understood. A growing body of literatureassociates peripheral blood levels of the antifibrotic hormone BNP (B-type natriuretic peptide) with atrial fibrillation (AF). Weinvestigated the relationship between pro-fibrotic tissue M2 macrophage marker Cluster of Differentiation (CD)163+, atrialprocollagen expression, and BNP gene expression in patients with and without AF.
METHODS AND RESULTS: In a cross-sectional study design, right atrial tissue was procured from 37 consecutive, consenting,stable patients without heart failure or left ventricular systolic dysfunction, of whom 10 had AF and 27 were non-AF controls.Samples were analyzed for BNP and fibro-inflammatory gene expression, as well as fibrosis and CD163+. Primary analysesshowed strong correlations (all P<0.008) between M2 macrophage CD163+ staining, procollagen gene expression, and myocardial BNP gene expression across the entire cohort. In secondary analyses without multiplicity adjustments, AF patients hadgreater left atrial volume index, more valve disease, higher serum BNP, and altered collagen turnover markers versus controls(all P<0.05). AF patients also showed higher atrial tissue M2 macrophage CD163+, collagen volume fraction, gene expressionof procollagen 1 and 3, as well as reduced expression of the BNP clearance receptor NPRC (all P<0.05). Atrial procollagen 3gene expression was correlated with fibrosis and BNP gene expression was correlated with serum BNP.
CONCLUSIONS: Elevated atrial tissue pro-fibrotic M2 macrophage CD163+ is associated with increased myocardial gene expression of procollagen and anti-fibrotic BNP and is higher in patients with AF. More work on modulation of BNP signaling fortreatment and prevention of AF may be warranted.
| Original language | English |
|---|---|
| Article number | e013416 |
| Number of pages | 12 |
| Journal | J Am Heart Assoc |
| Volume | 9 |
| Issue number | 11 |
| Early online date | 20 May 2020 |
| DOIs | |
| Publication status | Published - 02 Jun 2020 |