title: The ATP-binding cassette transporter BCRP1/ABCG2 plays a pivotal role in cardiac repair after myocardial infarction via modulation of microvascular endothelial cell survival and function.
abstract: OBJECTIVE
  To clarify the impact of breast cancer resistance protein 1 (BCRP1)/ATP-binding cassette transporter subfamily G member 2 (ABCG2) expression on cardiac repair after myocardial infarction (MI).
  
  
  RESULTS
  The ATP-binding cassette transporter BCRP1/ABCG2 is expressed in various organs, including the heart, and may regulate several tissue defense mechanisms. BCRP1/ABCG2 was mainly expressed in endothelial cells of microvessels in the heart. MI was induced in 8- to 12-week-old wild-type (WT) and Bcrp1/Abcg2 knockout (KO) mice by ligating the left anterior descending artery. At 28 days after MI, the survival rate was significantly lower in KO mice than in WT mice because of cardiac rupture. Echocardiographic, hemodynamic, and histological assessments showed that ventricular remodeling was more deteriorated in KO than in WT mice. Capillary, myofibroblast, and macrophage densities in the peri-infarction area at 5 days after MI were significantly reduced in KO compared with WT mice. In vitro experiments demonstrated that inhibition of BCRP1/ABCG2 resulted in accumulation of intracellular protoporphyrin IX and impaired survival of microvascular endothelial cells under oxidative stress. Moreover, BCRP1/ABCG2 inhibition impaired migration and tube formation of endothelial cells.
  
  
  CONCLUSIONS
  BCRP1/ABCG2 plays a pivotal role in cardiac repair after MI via modulation of microvascular endothelial cell survival and function.
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Higashikuni
authors.forename: Julie
authors.initials: J
authors.lastname: Sainz
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nakamura
authors.forename: Minoru
authors.initials: M
authors.lastname: Takaoka
authors.forename: Soichiro
authors.initials: S
authors.lastname: Enomoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwata
authors.forename: Makoto
authors.initials: M
authors.lastname: Sahara
authors.forename: Kimie
authors.initials: K
authors.lastname: Tanaka
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Koibuchi
authors.forename: Sumito
authors.initials: S
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kusuhara
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D002470:Cell Survival; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D055806:Microvessels / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000502:physiology*; D020127:Recovery of Function; D014945:Wound Healing
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins