Differential structural remodeling of the left-atrial posterior wall in patients affected by mitral regurgitation with or without persistent atrial fibrillation: A morphological and molecular study

Domenico Corradi, Sergio Callegari, Roberta Maestri, David Ferrara, Domenica Mangieri, Rossella Alinovi, Paola Mozzoni, Silvana Pinelli, Matteo Goldoni, Ylenia Adelaide Privitera, Veronica Bartoli, Ettore Astorri, Emilio MacChi, Augusto Vaglio, Stefano Benussi, Ottavio Alfieri

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Atrial fibrillation (AF) in mitral regurgitation (MR) is a complex disease where multiple factors may induce left-atrial structural remodeling (SR). We explored the differential SR of the left-atrial posterior wall (LAPW) of patients affected by MR with or without persistent AF, and the expression of key proteins involved in its pathogenesis. Methods and Results: Light microscopy of LAPW samples from 27 patients with MR and persistent AF (group 1), 33 with MR in sinus rhythm (group 2), and 15 autopsy controls (group 3) was used to measure myocyte diameter, percentage of myocytolytic myocytes, interstitial fibrosis, and capillary density; RT-PCR and Western blotting were used to assess the mRNA and protein levels of SOD-1, SOD-2, HO-1, calpain, MMP-2, MMP-9, TIMP-1, TIMP-2, and VEGF; immunofluorescence was used to locate these proteins. Myocyte diameter was similar in groups 1 and 2, but larger than controls. Compared to group 2, group 1 had more myocytolytic myocytes (20.8 ± 5.6% vs 14.7 ± 4.5%; P <0.0001), increased interstitial fibrosis (10.4 ± 5.1% vs 7.5 ± 4.2%; P <0.05), and decreased capillary density (923 ± 107 No/mm 2 vs 1,040 ± 100 No/mm 2; P <0.0001). All of the proteins were more expressed in groups 1 and 2 than in controls. The protein and mRNA levels of SOD-1, SOD-2, MMP-2, and MMP-9 were higher in group 1 than in group 2. Conclusions: The LAPW of MR patients with or without AF shows considerable SR. The former has more severe histopathological changes and higher levels of proteins involved in SR, thereby reaching a threshold beyond which the sinus impulse cannot normally activate atrial myocardium.

Original languageEnglish
Pages (from-to)271-279
Number of pages9
JournalJournal of Cardiovascular Electrophysiology
Volume23
Issue number3
DOIs
Publication statusPublished - Mar 2012

Keywords

  • atrial fibrillation
  • inflammation
  • left atrium
  • mitral regurgitation
  • remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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