Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation

Anne, W.; Willems, R.; Roskams, T.; Sergeant, P.; Herijgers, P.; Holemans, P.; Ector, H.; Heidbüchel, H.

doi:10.1016/J.CARDIORES.2005.04.016

Title

Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation

Author

Anne, W.

Willems, R.

Roskams, T.

Sergeant, P.

Herijgers, P.

Holemans, P.

Ector, H.

Heidbüchel, H.

Abstract

Background: Atrial fibrillation (AF) is associated with extracellular matrix remodeling involving atrial fibrosis and atrial dilatation. Angiotensin II mediated pathways and matrix metalloproteinases (MMPs) have been implicated in these processes. Our aim was to study atrial structural remodeling and the expression of the angiotensin receptor subtypes and MMPs and their inhibitors (TIMPs) in patients with mitral valve disease with and without AF. Methods and results: Biopsies from right and left atrial appendages (RA and LA) were taken from patients undergoing CABG (n=9, all in sinus rhythm (SR)) or mitral valve surgery (MVS; n = 19; 9 with permanent AF and 10 in SR). Patients with MVS and AF had significantly larger atria (versus MVS and SR: p=0.02; versus CABG: p < 0.01). The MVS patients had significantly more fibrosis than the control CABG group. Fibrosis was increased in both the AF and SR MVS groups in the LA, but only in the MVS-AF group in the RA. These AF patients had significantly more tricuspid regurgitation than SR patients. MMP-1 was down-regulated in LA of MVS patients (p=0.02) independent of the underlying rhythm (SR or AF; p=0.95). In RA biopsies, MMP-1 was down-regulated only in the MVS and AF group. MMP-9 was down-regulated in the MVS patients compared to CABG both in the RA and LA, and without a difference between the SR and AF groups. Protein expression of AT-1, AT-2, MMP-2, TIMP-1, -2 and -4, TNF-alpha, and TNF-alpha-converting enzyme did not differ significantly between the 3 groups. Conclusions: Concordant changes between NIMP-expression and fibrosis during mitral valve disease, both in LA and RA, suggest involvement of MMT's in structural atrial remodeling. AF itself did not contribute to altered fibrosis or MMP-expression in the LA. The association between AF and RA changes may be precipitated by greater hemodynainic load due to tricuspid regurgitation in these patients. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Language

English

Source (journal)

Cardiovascular research / European Society of Cardiology [Biot] - London

Publication

London : 2005

ISSN

0008-6363 [print]

1755-3245 [online]

DOI

10.1016/J.CARDIORES.2005.04.016

Volume/pages