title: Aliskiren suppresses atrial electrical and structural remodeling in a canine model of atrial fibrillation.
abstract: Aliskiren, a direct renin inhibitor is expected to achieve sufficient suppression of renin-angiotensin system. We evaluated the effect of aliskiren on the electrical and structural remodeling in a canine atrial fibrillation (AF) model. Twenty-eight dogs were divided into three groups: (1) pacing control group (n = 12), with continuous atrial rapid pacing for 3 or 6 weeks, (2) pacing + aliskiren group (n = 12), with oral aliskiren (30 mg/kg/day), and (3) sham group (n = 4), no pacing nor drug administration. Electrophysiological properties and AF inducibility were evaluated every week. After the protocol, the left atrial tissue was sampled for the further histological and mRNA analysis. The electrical remodeling, AF inducibility, the left atrial enlargement and interstitial fibrosis were observed in pacing control group and were more prominent in the 6-week protocol (vs. 3 week, p < 0.05). The mRNA expressions of matricellular proteins exhibited upregulation in 3-week pacing control, but these upregulations became insignificant in 6 weeks. In contrast, collagen type 3 exhibited significant upregulation in 6 week but not in 3-week protocol. These changes were suppressed in the pacing + aliskiren group. Aliskiren suppressed the atrial remodeling in a canine AF model. This effect was accompanied by the suppression of tissue fibrosis.
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0329, Japan. akira310@med.kitasato-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Satoh
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0329, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Niwano
authors.affiliation: Department of Education, Tamagawa University, College of Education, Machida, Japan.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Niwano
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0329, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kishihara
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0329, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Aoyama
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0329, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Oikawa
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0329, Japan.
authors.forename: Hidehira
authors.initials: H
authors.lastname: Fukaya
authors.affiliation: Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tamaki
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0329, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Ako
mesh_terms: D000577:Amides / Q000008:administration & dosage*; D000818:Animals; D001281:Atrial Fibrillation / Q000628:therapy*; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D004195:Disease Models, Animal; D004285:Dogs; D004452:Echocardiography; D005260:Female; D005355:Fibrosis; D005650:Fumarates / Q000008:administration & dosage*; D015870:Gene Expression; D006325:Heart Atria / Q000503:physiopathology*; D006439:Hemodynamics; D012083:Renin / Q000008:administration & dosage*; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D000577:Amides; D005650:Fumarates; C446481:aliskiren; D012083:Renin
keywords: Aliskiren; Atrial fibrillation; Atrial remodeling; Fibronectin1; Fibrosis