Korean Circ J.  2004 Jul;34(7):693-705. 10.4070/kcj.2004.34.7.693.

Gene Expression and Ultrastructural Remodeling in Persistent Atrial Fibrillation

• Hwang GS
• Kim YH
• Kim MK
• Lee JH
• Rha SW
• Lim DS
• Ro YM
• Park HL

• KMID: 1858922
• DOI: http://doi.org/10.4070/kcj.2004.34.7.693

Abstract

BACKGROUND
Atrial fibrillation (AF) has a tendency to become persistent over time and is known to induce atrial electrical, mechanical and ionic remodeling. However, the underlying mechanisms by which AF persists were not fully determined. The present study was carried out to assess alterations in the gene expression, including the oxidative stress-related genes of atrial myocardial cells in patients with persistent AF, and ultrastructural remodeling, as assessed by electron microscopy (EM) in pacing-induced sustained AF canine models.
METHODS
cDNA microarray technique and Western blot studies were performed, with tissue samples (right atrial appendage) from 10 patients, 4 with persistent AF and 6 used as controls, which had undergone coronary artery bypass surgery. Four dogs were subjected to continuous left atrial pacing at 400 bpm for at least 12 weeks to induce AF. One dog in sinus rhythm was used as a control sham operation. Tissue samples (1 mm3) were obtained from 4 sites of both atria for EM examination.
RESULTS
Thirty up-regulated and 25 down-regulated gene expressions were observed in the patients with AF. Eight of the up-regulated and 6 of the down-regulated genes were oxidative stress-related, which were confirmed by Western blot analyses. The characteristics of ultrastructural remodeling by persistent AF were: 1) an increased number of minimitochondria, 2) disarrayed myofilaments, 3) rarefaction of myofilaments, 4) disintegrated cristae and alignment in mitochondria and 5) vacuolization.
CONCLUSIONS
Persistent AF leads to alterations in the gene expression related to oxidative stress in the atrium, and also results in ultrastructural changes similar to those of an ischemia-reperfusion injury.

Keyword

Atrial fibrillation; Oxidative stress; Myocytes

MeSH Terms

Animals
Atrial Fibrillation*
Blotting, Western
Coronary Artery Bypass
Dogs
Gene Expression*
Humans
Microscopy, Electron
Mitochondria
Muscle Cells
Myofibrils
Oligonucleotide Array Sequence Analysis
Oxidative Stress
Reperfusion Injury