Mitochondrial dysfunction and redox signaling in atrial tachyarrhythmia
Alicja Bukowska1, Lorenz Schild, Gerburg Keilhoff
1University Hospital Magdeburg, Institute of Experimental Internal Medicine, Leipzigerstrasse 44, 39120 Magdeburg, Germany.
Experimental Biology and Medicine (Maywood, N.J.)
|April 1, 2008
Summary
Calcium overload contributes to atrial fibrillation by causing mitochondrial dysfunction and oxidative stress. This leads to increased expression of adhesion molecules and oxidative stress markers in atrial tissue.
Area of Science:
- Cardiovascular Research
- Mitochondrial Biology
- Molecular Cardiology
Background:
- Atrial remodeling in atrial fibrillation (AF) is linked to calcium overload and oxidative stress.
- Remodeling increases thrombogenicity via elevated adhesion molecule expression.
Purpose of the Study:
- To investigate mitochondrial dysfunction and oxidative stress signaling pathways in AF atrial tissue.
- To assess the role of calcium influx in AF-related molecular changes.
Main Methods:
- Ex vivo human atrial tissue analysis (AF patients vs. controls).
- In vitro rapid pacing of human atrial tissue slices.
- Mitochondrial electron microscopy and respiration assays.
- Gene expression (RT-PCR) and protein analysis (immunoblot, ELISA, gel-shift assays).
Main Results:
- AF atrial tissue showed impaired mitochondrial structure and respiration, increased oxidative stress.
- Nuclear factor-kappaB (NF-kappaB) accumulation and elevated ICAM-1, HO-1, and LOX-1 expression were observed.
- Rapid pacing mimicked these changes; verapamil blocked them, as did antioxidants and an angiotensin II receptor blocker.
Conclusions:
- Calcium influx through L-type channels drives oxidative stress and mitochondrial dysfunction in AF.
- This process upregulates oxidative stress markers and adhesion molecules, contributing to atrial remodeling.
- Targeting calcium channels or oxidative stress pathways may offer therapeutic strategies for AF.
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