title: Is structural remodeling of fibrillated atria the consequence of tissue hypoxia?
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.
  
  
  RESULTS
  Changes in the expression of vascular endothelial growth factor (VEGF), VEGF receptors, and hypoxia-induced transcription factor-1alpha (HIF-1alpha) 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-1alpha 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-1alpha 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-1alpha, 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.
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Science, Hiroshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ogi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakano
authors.forename: Shumpei
authors.initials: S
authors.lastname: Niida
authors.forename: Keigo
authors.initials: K
authors.lastname: Dote
authors.forename: Yukoh
authors.initials: Y
authors.lastname: Hirai
authors.forename: Kazuyosi
authors.initials: K
authors.lastname: Suenari
authors.forename: Yukiji
authors.initials: Y
authors.lastname: Tonouchi
authors.forename: Noboru
authors.initials: N
authors.lastname: Oda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Makita
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Ueda
authors.forename: Kenta
authors.initials: K
authors.lastname: Kajihara
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Imai
authors.forename: Taijro
authors.initials: T
authors.lastname: Sueda
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kihara
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000201:enzymology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis* / Q000235:genetics; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis* / Q000235:genetics
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9