Science｜周斌/吕爱兰合作揭示心肌缺血后新生冠状侧支动脉形成机制

TL;DR - A Science study used multiple genetic lineage-tracing systems to show that most new coronary collateral arteries formed after myocardial ischemia arise from capillary endothelial cells, not rearranged pre-existing arteries. It also identified a VEGFA-driven epigenetic pathway that could inform regenerative treatments for ischemic heart disease.

• Dual-recombinase tracing and a tamoxifen-independent synNotch recording system addressed limitations of prior Cx40-CreER lineage studies.
• Most de novo collateral arteries originated through capillary-to-artery conversion; ablating these vessels increased fibrosis and myocardial damage.
• Transient VEGFA expression via modified mRNA promoted functional artery formation, reduced cardiac scarring, and improved heart function, whereas sustained VEGF receptor activation impaired vessel maturation.
• VEGFA induced YY1, which recruited SETD1A to increase H3K4me3 and HES1 transcription, driving endothelial cells toward an arterial fate.