Atrial fibrillation is associated with cardiac hypoxia

Gramley, Felix; Lorenzen, Johann; Jedamzik, Britta; Gatter, Kevin; Koellensperger, Eva; Munzel, Thomas; Pezzella, Francesco

doi:10.1016/j.carpath.2008.11.001

« Previous Next »Cardiovascular Pathology
Volume 19, Issue 2 , Pages 102-111, March 2010

Atrial fibrillation is associated with cardiac hypoxia

Felix Gramley
- Department of Cardiology and Vascular Medicine, Mainz University, Germany
- Corresponding author. Department of Cardiology and Vascular Medicine, University Hospital Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. Tel.: +49 6131 170.
Johann Lorenzen
- Institute for Pathology, RWTH Aachen University, Germany
Britta Jedamzik
- Institute for Pathology, RWTH Aachen University, Germany
Kevin Gatter
- Nuffield Department of Clinical Laboratory Sciences, Oxford University, UK
Eva Koellensperger
- Department for Plastic and Hand Surgery, University of Heidelberg, Germany
Thomas Munzel
- Department of Cardiology and Vascular Medicine, Mainz University, Germany
Francesco Pezzella
- Nuffield Department of Clinical Laboratory Sciences, Oxford University, UK

Received 8 January 2008; received in revised form 2 November 2008; accepted 18 November 2008. published online 12 February 2009.

Abstract

Background

Atrial fibrillation (AF), the most common human arrhythmia, is responsible for substantial morbidity and mortality and may be promoted by selective atrial ischemia and atrial fibrosis. Consequently, we investigated markers for hypoxia and angiogenesis in AF.

Methods

Right atrial appendages (n=158) were grouped according to heart rhythm [sinus rhythm (SR) or AF]. The degree of fibrosis and microvessel density of all patients were determined morphometrically using Sirius-Red- and CD34/CD105-stained sections, respectively. Next, sections (n=77) underwent immunostaining to detect hypoxia- and angiogenesis-related proteins [hypoxia-inducible factor (HIF)1α, HIF2α, vascular endothelial growth factor (VEGF), VEGF receptor 2 (KDR), phosphorylated KDR (pKDR), carboanhydrase IX, platelet-derived growth factor] and the apoptosis-related B-cell lymphoma 2 protein.

Results

Fibrosis progressed significantly from 14.7±0.8% (SR) to 22.3±1.4% (AF). While the positive cytoplasmic staining of HIF1α, HIF2α, VEGF, KDR, and pKDR rose significantly from SR to AF, their nuclear fractions fell (only pKDR significantly). The median CD34/CD105-positive microvessel size increased significantly from SR to AF.

Conclusions

AF is closely associated with an atrial up-regulation of hypoxic and angiogenic markers. Whether this is cause, effect, or co-phenomenon of fibrosis remains to be investigated. It is conceivable that fibrosis might lead to an increased O₂ diffusion distance and thus induce ischemic signaling, which, in turn, leads to angiogenesis.

Keywords: Atrial, Hypoxia, HIF1, Fibrosis, Arrhythmia, Angiogenesis