ATP-binding cassette transporter Abcg2 lineage contributes to the cardiac vasculature after oxidative stress.

ABSTRACT

Due to their specialized location, stem and progenitor cells are often exposed to oxidative stress. Although ATP-binding cassette transporter subfamily G member 2 (Abcg2)-expressing cells have been implicated in cardiac protective mechanisms involving oxidative stress, there remains a lack of understanding regarding the behavior of cardiac Abcg2-expressing cells when exposed to ROS. The aim of the present study was to characterize the response of the cardiac Abcg2 lineage to oxidative stress. In vitro analysis demonstrated that the antioxidant program regulated by Abcg2 is dependent on a functional transporter. Delivery of paraquat dichloride (PQ), a systemic oxidative stress-inducing agent, to mice confirmed that Abcg2 provides a survival benefit. When exposed to PQ, reporter mice showed an increase in the Abcg2 lineage. Transcriptional and immunohistochemical analysis of Abcg2 lineage-positive cells revealed an enhanced vascular commitment after stress. Finally, preconditioning with PQ demonstrated a reduction in scar size and an increase in angiogenesis after permanent left coronary artery ligation. In conclusion, the data suggest that Abcg2 plays a cytoprotective role in response to in vivo oxidative stress. The contribution of the Abcg2 lineage to the vasculature in the heart is increased after PQ delivery.