Abstract 17106: Transition From Adipose to Fibrotic Tissue in the Atrial Subepicardium in Humans and in a Sheep Model of Atrial Fibrillation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Peter Haemers ◽  
Hadhami Hamdi ◽  
Piet Claus ◽  
Patrick Farahmand ◽  
Patrick Bruneval ◽  
...  

Epicardial adipose tissue (EAT) is recognized as potentially involved in the pathophysiology of atrial fibrillation (AF). In addition to EAT fatty infiltration commonly observed in myocardium might be also associated with the substrate for AF. We conducted a histological study in 93 human right atrial samples obtained during cardiac surgery and in a sheep model of long-term persistent AF (PAF) induced by atrial tachypacing (24±8 weeks) (15 PAF, 11 SR). Upon Sirius Red and Harris Haematoxylin staining, human atria showed various degree of fatty infiltration starting from the epicardium (rarely from vessels), which could be associated with various degree of subepicardial fibrosis realizing in some cases a true fibro-fatty infiltration. The extent of remodeled epicardium was assessed as % of infiltrating and fibrotic epicardium±adipose tissue to total epicardial length; 44±26 % of the epicardium was remodeled. A multiple regression model (including history of AF, % adipose tissue, age, BodyMassIndex, coronary artery bypass, ejection fraction) significantly predicted the percentage of epicardial remodeling (R=0.501, p=0.003). Only AF and the % adipose tissue were significant predictors (respectively β=0.27;p=0.016 and β=-0.267;p=0.016). To further analyze the relationship between fibro-fatty infiltration and AF, a histological study was performed in LA specimen of a sheep PAF model which revealed 4 grades of subepicardial infiltrates from pure fatty to dense fibro-fatty infiltration (fig A). EAT infiltrates (316) were graded, demonstrating a shift towards more severe grades in the AF group p<0.0001) (fig B). Inflammatory cells were detected in 14 fatty infiltrations (grade 2 and 3) of 6 AF sheep (and only in 1 fatty infiltration of SR sheep). Conclusion: , AF is associated with the transformation of fat into fibro-fatty infiltrations suggesting that the subepicardial adipose tissue plays a role in the atrial fibrotic remodeling.

2012 ◽  
Vol 44 (3) ◽  
pp. 211-219 ◽  
Author(s):  
Nicola Cooley ◽  
Mark J. Cowley ◽  
Ruby C. Y. Lin ◽  
Silvana Marasco ◽  
Chiew Wong ◽  
...  

Chronic atrial fibrillation (AF) is a complication associated with the dilated atria of patients with valvular heart disease and contributes to worsened pathology. We examined microRNA (miRNA) expression profiles in right and left atrial appendage tissue from valvular heart disease (VHD) patients. Right atrial (RA) appendage from patients undergoing coronary artery bypass grafting and left atrial (LA) appendage from healthy hearts, not used for transplant, were used as controls. There was no detectable effect of chronic AF on miRNA expression in LA tissue, but miRNA expression in RA was strongly influenced by AF, with 47 miRNAs (15 higher, 32 lower) showing differential expression between the AF and control sinus rhythm groups. VHD induced different changes in miRNA expression in LA compared with RA. Fifty-three (12 higher, 41 lower) miRNAs were altered by VHD in LA, compared with 5 (4 higher, 1 lower) in RA tissue. miRNA profiles also differed between VHD-LA and VHD-RA (13 higher, 26 lower). We conclude that VHD and AF influence miRNA expression patterns in LA and RA, but these are affected differently by disease progression and by the development of AF. These findings provide new insights into the progression of VHD.


2016 ◽  
Vol 220 ◽  
pp. 580-588 ◽  
Author(s):  
Junaid A.B. Zaman ◽  
Leanne Harling ◽  
Hutan Ashrafian ◽  
Ara Darzi ◽  
Nigel Gooderham ◽  
...  

EP Europace ◽  
2005 ◽  
Vol 7 (2) ◽  
pp. 170-174 ◽  
Author(s):  
T HAKALA ◽  
A VALTOLA ◽  
A TURPEINEN ◽  
A HEDMAN ◽  
R VUORENNIEMI ◽  
...  

2020 ◽  
Vol 126 (10) ◽  
pp. 1330-1342 ◽  
Author(s):  
Nadine Suffee ◽  
Thomas Moore-Morris ◽  
Bernd Jagla ◽  
Nathalie Mougenot ◽  
Gilles Dilanian ◽  
...  

Rationale: Fibro-fatty infiltration of subepicardial layers of the atrial wall has been shown to contribute to the substrate of atrial fibrillation. Objective: Here, we examined if the epicardium that contains multipotent cells is involved in this remodeling process. Methods and Results: One hundred nine human surgical right atrial specimens were evaluated. There was a relatively greater extent of epicardial thickening and dense fibro-fatty infiltrates in atrial tissue sections from patients aged over 70 years who had mitral valve disease or atrial fibrillation when compared with patients aged less than 70 years with ischemic cardiomyopathy as indicated using logistic regression adjusted for age and gender. Cells coexpressing markers of epicardial progenitors and fibroblasts were detected in fibro-fatty infiltrates. Such epicardial remodeling was reproduced in an experimental model of atrial cardiomyopathy in rat and in Wilms tumor 1 (WT1) CreERT2/+ ;ROSA-tdT +/− mice. In the latter, genetic lineage tracing demonstrated the epicardial origin of fibroblasts within fibro-fatty infiltrates. A subpopulation of human adult epicardial-derived cells expressing PDGFR (platelet-derived growth factor receptor)-α were isolated and differentiated into myofibroblasts in the presence of Ang II (angiotensin II). Furthermore, single-cell RNA-sequencing analysis identified several clusters of adult epicardial-derived cells and revealed their specification from adipogenic to fibrogenic cells in the rat model of atrial cardiomyopathy. Conclusions: Epicardium is reactivated during the formation of the atrial cardiomyopathy. Subsets of adult epicardial-derived cells, preprogrammed towards a specific cell fate, contribute to fibro-fatty infiltration of subepicardium of diseased atria. Our study reveals the biological basis for chronic atrial myocardial remodeling that paves the way of atrial fibrillation.


2016 ◽  
Vol 788 ◽  
pp. 286-293 ◽  
Author(s):  
Torsten Christ ◽  
Peter P. Kovács ◽  
Karoly Acsai ◽  
Michael Knaut ◽  
Thomas Eschenhagen ◽  
...  

2020 ◽  
Vol 109 (10) ◽  
pp. 1271-1281
Author(s):  
Linghe Wu ◽  
R. W. Emmens ◽  
J. van Wezenbeek ◽  
W. Stooker ◽  
C. P. Allaart ◽  
...  

Abstract Objective Inflammation of the atria is an important factor in the pathogenesis of atrial fibrillation (AF). Whether the extent of atrial inflammation relates with clinical risk factors of AF, however, is largely unknown. This we have studied comparing patients with paroxysmal and long-standing persistent/permanent AF. Methods Left atrial tissue was obtained from 50 AF patients (paroxysmal = 20, long-standing persistent/permanent = 30) that underwent a left atrial ablation procedure either or not in combination with coronary artery bypass grafting and/or valve surgery. Herein, the numbers of CD45+ and CD3+ inflammatory cells were quantified and correlated with the AF risk factors age, gender, diabetes, and blood CRP levels. Results The numbers of CD45+ and CD3+ cells were significantly higher in the adipose tissue of the atria compared with the myocardium in all AF patients but did not differ between AF subtypes. The numbers of CD45+ and CD3+ cells did not relate significantly to gender or diabetes in any of the AF subtypes. However, the inflammatory infiltrates as well as CK-MB and CRP blood levels increased significantly with increasing age in long-standing persistent/permanent AF and a moderate positive correlation was found between the extent of atrial inflammation and the CRP blood levels in both AF subtypes. Conclusion The extent of left atrial inflammation in AF patients was not related to the AF risk factors, diabetes and gender, but was associated with increasing age in patients with long-standing persistent/permanent AF. This may be indicative for a role of inflammation in the progression to long-standing persistent/permanent AF with increasing age. Graphic abstract


2014 ◽  
Vol 2 (4) ◽  
pp. 127 ◽  
Author(s):  
Ali Ü Yener ◽  
Adem Bekler ◽  
M Turgut A Özkan ◽  
Mesut Erbaş ◽  
Sedat Özcan ◽  
...  

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