title: Low Cardiac Output Leads Hepatic Fibrosis in Right Heart Failure Model Rats.
abstract: BACKGROUND
  Hepatic fibrosis progresses with right heart failure, and becomes cardiac cirrhosis in a severe case. Although its causal factor still remains unclear. Here we evaluated the progression of hepatic fibrosis using a pulmonary artery banding (PAB)-induced right heart failure model and investigated whether cardiac output (CO) is responsible for the progression of hepatic fibrosis.
  
  
  RESULTS
  Five-week-old Sprague-Dawley rats divided into the PAB and sham-operated control groups. After 4 weeks from operation, we measured CO by echocardiography, and hepatic fibrosis ratio by pathological examination using a color analyzer. In the PAB group, CO was significantly lower by 48% than that in the control group (78.2±27.6 and 150.1±31.2 ml/min, P<0.01). Hepatic fibrosis ratio and serum hyaluronic acid, an index of hepatic fibrosis, were significantly increased in the PAB group than those in the control group (7.8±1.7 and 1.0±0.2%, P<0.01, 76.2±27.5 and 32.7±7.5 ng/ml, P<0.01). Notably, the degree of hepatic fibrosis significantly correlated a decrease in CO. Immunohistological analysis revealed that hepatic stellate cells were markedly activated in hypoxic areas, and HIF-1α positive hepatic cells were increased in the PAB group. Furthermore, by real-time PCR analyses, transcripts of profibrotic and fibrotic factors (TGF-β1, CTGF, procollargen I, procollargen III, MMP 2, MMP 9, TIMP 1, TIMP 2) were significantly increased in the PAB group. In addition, western blot analyses revealed that the protein level of HIF-1α was significantly increased in the PAB group than that in the control group (2.31±0.84 and 1.0±0.18 arbitrary units, P<0.05).
  
  
  CONCLUSIONS
  Our study demonstrated that low CO and tissue hypoxia were responsible for hepatic fibrosis in right failure heart model rats.
authors: Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan.|Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
authors: Yoshitaka
authors: Y
authors: Fujimoto
authors: Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
authors: Takashi
authors: T
authors: Urashima
authors: Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan.
authors: Daisuke
authors: D
authors: Shimura
authors: Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
authors: Reiji
authors: R
authors: Ito
authors: Division of Cardiology, Saitama Children's Medical Center, Saitama, Japan.
authors: Sadataka
authors: S
authors: Kawachi
authors: Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan.
authors: Ichige
authors: I
authors: Kajimura
authors: Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan.
authors: Toru
authors: T
authors: Akaike
authors: Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan.
authors: Yoichiro
authors: Y
authors: Kusakari
authors: Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
authors: Masako
authors: M
authors: Fujiwara
authors: Division of Cardiology, Saitama Children's Medical Center, Saitama, Japan.
authors: Kiyoshi
authors: K
authors: Ogawa
authors: Department of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan.
authors: Nobuhito
authors: N
authors: Goda
authors: Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
authors: Hiroyuki
authors: H
authors: Ida
authors: Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan.
authors: Susumu
authors: S
authors: Minamisawa
mesh_terms: D000818:Animals; D002303:Cardiac Output, Low / Q000097:blood / Q000150:complications*; D015687:Cell Hypoxia; D004195:Disease Models, Animal; D015870:Gene Expression; D006333:Heart Failure / Q000097:blood / Q000150:complications*; D006820:Hyaluronic Acid / Q000097:blood; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology*; D008297:Male; D058628:Myofibroblasts / Q000473:pathology; D017207:Rats, Sprague-Dawley
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D006820:Hyaluronic Acid