title: Importance of Pulmonary Vein Preferential Fibrosis for Atrial Fibrillation Promotion in Hypertensive Rat Hearts.
abstract: Hypertension is one of the independent risk factors for atrial fibrillation (AF). Pulmonary veins (PVs) play an important role as the substrate for AF and triggers of AF. The purpose of this study was to determine the structural remodelling of the PVs and its effect on promoting AF in hypertensive (HT) rat hearts.
  
  
  
  Eighteen-week-old Dahl salt-sensitive HT rats and their controls were used for histological and immunohistological analyses, and electrophysiological studies were performed in Langendorff perfused hearts.
  
  
  
  Masson-trichrome staining revealed that hypertension significantly increased the fibrosis in the PVs, particularly in subendocardial and perivascular areas, compared with that in control rats, however, at this early stage of hypertension, left atrial fibrosis was not prominent. In the HT rat hearts with PVs, electrical stimulation significantly increased the number of repetitive atrial firing and atrial tachycardia inducibility, which significantly diminished after the excision of the PVs. An immunofluorescent analysis revealed that HT rats had PV specific endocardial smooth muscle actin (αSMA)-positive cells with remarkable proliferation of platelet-derived growth factor (PDGF)-C and vascular endothelial growth factor (VEGF), which was lacking in the left atrial structures of the control and the HT rats. Pretreatment with imatinib, a PDGF receptor activity blocker, in HT rats reduced the αSMA-positive cell proliferation and fibrosis in the PVs and also induced a significant reduction in VEGF expression. Also, the drug pretreatment effectively prevented repetitive atrial firing promotion without affecting the blood pressure.
  
  
  
  PV preferential fibrosis might play an important role in the arrhythmogenic substrate of AF in HT rat hearts.
authors.affiliation: The Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan. Electronic address: iwasaki@nms.ac.jp.
authors.forename: Yu-Ki
authors.initials: YK
authors.lastname: Iwasaki
authors.affiliation: The Cardiovascular Institute, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: The Cardiovascular Institute, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sekiguchi
authors.affiliation: The 4th Department of Internal Medicine, Teikyo University School of Medicine, Kanagawa, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Hayami
authors.affiliation: The Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005355:Fibrosis / Q000473:pathology; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D066298:In Vitro Techniques; D009206:Myocardium / Q000473:pathology*; D011667:Pulmonary Veins / Q000473:pathology*; D051381:Rats; D020303:Rats, Inbred Dahl; D012307:Risk Factors