title: The ATP-binding cassette transporter ABCG2 protects against pressure overload-induced cardiac hypertrophy and heart failure by promoting angiogenesis and antioxidant response.
abstract: OBJECTIVE
  ATP-binding cassette transporter subfamily G member 2 (ABCG2), expressed in microvascular endothelial cells in the heart, has been suggested to regulate several tissue defense mechanisms. This study was performed to elucidate its role in pressure overload-induced cardiac hypertrophy.
  
  
  RESULTS
  Pressure overload was induced in 8- to 12-week-old wild-type and Abcg2-/- mice by transverse aortic constriction (TAC). Abcg2-/- mice showed exaggerated cardiac hypertrophy and ventricular remodeling after TAC compared with wild-type mice. In the early phase after TAC, functional impairment in angiogenesis and antioxidant response in myocardium was found in Abcg2-/- mice. In vitro experiments demonstrated that ABCG2 regulates transport of glutathione, an important endogenous antioxidant, from microvascular endothelial cells. Besides, glutathione transported from microvascular endothelial cells in ABCG2-dependent manner ameliorated oxidative stress-induced cardiomyocyte hypertrophy. In vivo, glutathione levels in plasma and the heart were increased in wild-type mice but not in Abcg2-/- mice after TAC. Treatment with the superoxide dismutase mimetic ameliorated cardiac hypertrophy in Abcg2-/- mice after TAC to the same extent as that in wild-type mice, although cardiac dysfunction with impaired angiogenesis was observed in Abcg2-/- mice.
  
  
  CONCLUSIONS
  ABCG2 protects against pressure overload-induced cardiac hypertrophy and heart failure by promoting angiogenesis and antioxidant response.
authors: Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan.
authors: Yasutomi
authors: Y
authors: Higashikuni
authors: Julie
authors: J
authors: Sainz
authors: Kazuto
authors: K
authors: Nakamura
authors: Minoru
authors: M
authors: Takaoka
authors: Soichiro
authors: S
authors: Enomoto
authors: Hiroshi
authors: H
authors: Iwata
authors: Kimie
authors: K
authors: Tanaka
authors: Makoto
authors: M
authors: Sahara
authors: Yasunobu
authors: Y
authors: Hirata
authors: Ryozo
authors: R
authors: Nagai
authors: Masataka
authors: M
authors: Sata
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005838:Genotype; D005978:Glutathione / Q000097:blood / Q000378:metabolism*; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D006614:Hindlimb; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007511:Ischemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000098:blood supply; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D018384:Oxidative Stress / Q000187:drug effects; D010641:Phenotype; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014162:Transfection; D016276:Ventricular Function; D020257:Ventricular Remodeling
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; D000975:Antioxidants; D009363:Neoplasm Proteins; D005978:Glutathione