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.
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.
Higashikuni
Yasutomi
Y
Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan.
Sainz
Julie
J
Nakamura
Kazuto
K
Takaoka
Minoru
M
Enomoto
Soichiro
S
Iwata
Hiroshi
H
Sahara
Makoto
M
Tanaka
Kimie
K
Koibuchi
Nobutaka
N
Ito
Sumito
S
Kusuhara
Hiroyuki
H
Sugiyama
Yuichi
Y
Hirata
Yasunobu
Y
Nagai
Ryozo
R
Sata
Masataka
M
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
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins