Capillaries drive new collateral artery formation after heart blockage

New research in mice challenges a long-standing view of how the heart builds backup blood vessels after a coronary artery blockage, showing that new collateral arteries arise primarily from capillaries rather than existing arteries.

The findings offer insight into a molecular pathway that could be leveraged to promote cardiac repair. Coronary artery disease – a leading cause of death worldwide – can result in blocked blood flow to heart muscle, causing heart attacks. Although medical procedures like stents and bypass surgery can restore circulation, they are invasive, pose risks, and are not always effective. As such, there is a need for alternative approaches.

Coronary collateral arteries act as natural bypasses, diverting blood around blocked vessels and improving outcomes after injury. Developing ways to stimulate the formation of collateral arteries could therefore provide an important therapeutic strategy. Traditionally, coronary collaterals were thought to form when preexisting arterial connections enlarge in response to increased blood-flow forces following an obstruction. Yet recent research has shown that these vessels can arise de novo, with arterial endothelial cells playing a central role in their development. However, the mechanisms by which these vessels arise remain poorly understood.

To address this gap, Mingjun Zhang and colleagues used genetically engineered mouse models and dual genetic lineage-tracing tools to track the origins of different types of endothelial cells during coronary collateral formation. Zhang et al. found that capillary endothelial cells, rather than arterial endothelial cells, are major building blocks of new coronary collaterals. The conversion of capillaries into collateral arteries is essential for cardiac repair. The authors also identified a VEGF-driven molecular pathway that promotes this capillary-to-artery conversion, pointing to a potential strategy for enhancing de novo collateral formation and cardiac repair.