(A) Neonatal (P2) hearts subjected to left coronary artery ligation are able to restore blood flow to the injured region through the formation of collateral arteries by arterial reassembly. After the regenerative window (P7) hearts subjected to left coronary artery (LCA) ligation do not form collateral arteries.
(B) Neonatal hearts lacking Cxcr4 in the arterial endothelial cells or Cxcl12 in the capillary bed are unable to recruit arterial endothelial cells (AECs) for arterial reassembly and form fibrotic scars after LCA ligation. Collateral artery reassembly is triggered by CXCL12-expressing capillaries, which activate and recruit CXCR4-expressing AECs to migrate, proliferate, and form new collateral arteries.
(C)The injection of a high dose of CXCL12 rescues the formation of collateral arteries in P7 hearts.