title: Novel strategy to prevent atrial fibrosis and fibrillation.
abstract: To explore a novel strategy of preventing atrial fibrosis and atrial fibrillation (AF), we have established 3 appropriate experimental models of AF. Firstly, atrial fibrosis was induced by pressure overload by abdominal aortic constriction (AAC). AAC enhanced left atrial (LA) expression of monocyte chemoattractant protein-1. Scanning electron microscopy revealed that LA endothelial cells were irregularly hypertrophied, with disarrangement of lines of cells. Possible "arrested" leukocyte-derived cells were observed on the surface of LA endothelial cells. Treatment with pioglitazone, a peroxisome proliferator-activated receptor-γ agonist, resulted in attenuation of pressure overload-induced LA fibrosis. Secondly, LA fibrosis was induced by continuous infusion of angiotensin II (AII). Repeated whole-body hyperthermia led to the induction of heat shock protein (HSP) 72, which resulted in attenuation of AII-induced LA fibrosis. Thirdly, atrial fibrosis was induced by 5/6 nephrectomy as a model of AF associated with chronic kidney disease. Because the amount of nicotinamide adenine dinucleotide phosphate oxidase was increased and the potent antioxidant agent was effective, oxidative stress may be involved in the pathogenesis of LA fibrosis and enhanced AF vulnerability in this model. These observations suggest that inflammatory profibrotic processes are essential for the development of atrial fibrosis in these 3 models. Pioglitazone, induction of HSPs and antioxidant agent could be novel therapeutic approaches to preventing atrial fibrosis and AF.
authors.affiliation: Department of Laboratory Examination and Diagnostics, Oita University Faculty of Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Oita 879-5593, Japan. takanao@oita-u.ac.jp
authors.forename: Naohiko
authors.initials: N
authors.lastname: Takahashi
authors.forename: Osamu
authors.initials: O
authors.lastname: Kume
authors.forename: Osamu
authors.initials: O
authors.lastname: Wakisaka
authors.forename: Naoya
authors.initials: N
authors.lastname: Fukunaga
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Teshima
authors.forename: Masahide
authors.initials: M
authors.lastname: Hara
authors.forename: Tetsunori
authors.initials: T
authors.lastname: Saikawa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D005786:Gene Expression Regulation; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007035:Hypothermia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D047495:PPAR gamma / Q000096:biosynthesis; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D050884:HSP72 Heat-Shock Proteins; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone