Collateral artery is a unique artery sub-type that connects a healthy perfused artery to an injured artery, providing an alternate route for blood flow and allowing preservation of affected tissue. Only a small percentage of patients with coronary artery disease develop collateral arteries and have been correlated with improved survivability. Hence, stimulating formation of coronary collateral arteries in rest of the patient population, that fail to develop them, may improve their prognosis. Our goal is to identify cellular and molecular drivers of collateral artery formation and stimulate them in injured hearts. Our current work has revealed a unique way neonatal mouse heart builds collateral artery and preserves myocardial function in response to coronary artery blockage. Upon occlusion, single artery cells migrate out of their resident arteries, proliferate and coalesce with each other to create collateral artery connections. Blood flow through these collateral arteries then stimulates cardiomyocyte proliferation and facilitates neonatal heart regeneration. This cellular process, termed as Artery Reassembly, is driven by CXCL12/CXCR4 chemokine signaling axis. Artery Reassembly was restricted to early neonatal stages and did not occur in later stages. However, one exogenous dose of a chemokine, CXCL12, allowed the adult hearts to build collateral arteries by Artery Reassembly an improved their heart function after myocardial infarction.

Key words: Coronary arteries, Collateral arteries, Endothelial cells, Heart Regeneration, CXCL12