Heme oxygenase-1 expression in the left atrial myocardium of patients with chronic atrial fibrillation related to mitral valve disease: its regional relationship with structural remodeling

Domenico Corradi, Sergio Callegari, Roberta Maestri, Stefano Benussi, Silvia Bosio, Giuseppe De Palma, Rossella Alinovi, Andrea Caglieri, Matteo Goldoni, Paola Mozzoni, Paolo Pastori, Laura Manotti, Simona Nascimbene, Enrica Dorigo, Raffaella Rusconi, Ettore Astorri, Ottavio Alfieri

Research output: Contribution to journalArticlepeer-review

Abstract

Atrial fibrillation becomes a self-perpetuating arrhythmia as a consequence of electrophysiogic and structural remodeling involving the atrium. Oxidative stress may be a link between this rhythm disturbance and electrophysiogic remodeling. The aim of this study was to evaluate whether the heme oxygenase-1 (HO-1) marker of oxidative stress was more expressed in left atrial sites with stronger structural remodeling in patients affected by chronic atrial fibrillation (CAF) and mitral valve disease (MD). Myocardial samples were taken from the left atrial posterior wall (LAPW) and left atrial appendage (LAA) of 24 patients with CAF-MD in addition to 10 autopsy controls. The levels of HO-1 messenger RNA (mRNA) and HO-1 protein in each pathologic LAPW and LAA were quantified using reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Furthermore, light microscopy was used to morphometrically evaluate the differential myocyte and interstitial changes in the same CAF-MD LAPW and LAA samples. In controls, HO-1 protein was quantified using enzyme-linked immunosorbent assay. Unlike controls, patients with CAF-MD had higher levels of HO-1 mRNA and its protein product, expressed as LAPW/LAA ratios, in the LAPW (2.18 ± 1.18, P <.0001, and 1.55 ± 0.67, P <.005), and their LAPW also showed greater histologic changes in myocytolytic myocytes (15.1% ± 3.1% versus 6.9% ± 3.3%, P <.0001), interstitial fibrosis (8.2% ± 2.2% versus 2.8% ± 1.2%, P <.0001), and capillary density (816 ± 120 number/mm2 versus 1114 ± 188 number/mm2; P <.05). In addition, markers of oxidative stress were immunohistochemically studied with antinitrotyrosine and anti-iNOS antibodies. In patients with CAF-MD, the inducible enzyme HO-1 is more expressed in the left atrial areas that show greater structural remodeling. This finding strongly suggests a pathogenetic relationship between oxidative stress and the degree of histologic change.

Original languageEnglish
Pages (from-to)1162-1171
Number of pages10
JournalHuman Pathology
Volume39
Issue number8
DOIs
Publication statusPublished - Aug 2008

Keywords

  • Atrial fibrillation
  • Heme oxygenase-1
  • Mitral valve disease
  • Oxidative stress
  • Structural remodeling

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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