Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Arrhythmia/Electrophysiology
Is Structural Remodeling of Fibrillated Atria the Consequence of Tissue Hypoxia?
Hiroshi Ogi, Yukiko Nakano, Shumpei Niida, Keigo Dote, Yukoh Hirai, Kazuyosi Suenari, Yukiji Tonouchi, Noboru Oda, Yuko Makita, Shigeyuki Ueda, Kenta Kajihara, Katsuhiko Imai, Taijro Sueda, Kazuaki Chayama, Yasuki Kihara
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Keywords: Atrial fibrillation, Hypoxia, Hypoxia-induced transcription factor-1α (HIF-1α), Matrix metalloproteinase 9 (MMP-9), Vascular endothelial growth factor (VEGF)
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2010 Volume 74 Issue 9 Pages 1815-1821

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Abstract

Background: Matrix metalloproteinases (MMPs) play an important role in degradation of the extracellular matrix of injured tissue. MMP-9 expression increases in fibrillating atrial tissue; however, the mechanism for this increase has not been clarified. Methods and Results: Changes in the expression of vascular endothelial growth factor (VEGF), VEGF receptors, and hypoxia-induced transcription factor-1α (HIF-1α) in fibrillating atrial tissue were investigated. Atrial tissue samples were obtained from 13 patients with atrial fibrillation (AF) and 25 patients without a history of AF (regular sinus rhythm, RSR) undergoing cardiac operations. Western blot, real-time polymerase chain reaction, and immunofluorescence analyses of the expression of VEGF, VEGF receptors, and HIF-1α were performed. The VEGF mRNA and protein levels increased significantly in the AF group compared with the RSR group (P<0.05), and the expression of HIF-1α protein was also significantly higher in the AF group. VEGF receptor-1 mRNA, a high-affinity receptor for VEGF, but not VEGF receptor-2 mRNA, was upregulated in the atria of the AF group (P<0.05). Immunofluorescence staining revealed excess production and co-localization of HIF-1α, VEGF and MMP-9 in the endothelium of the atrial arteries in the AF group. Conclusions: It is possible that upregulation of HIF-1/VEGF is involved in the enhancement of MMP-9 expression under hypoxic conditions.  (Circ J 2010; 74: 1815 - 1821)

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© 2010 THE JAPANESE CIRCULATION SOCIETY
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