The prevalence of complex multivessel coronary artery and peripheral vascular disease is steadily rising and it is especially this patient population that will benefit from adjunct therapy to conventional revascularization methods. The recent failures of clinical therapeutic angiogenesis trials emphasize a need for a more rational approach to this important area of clinical cardiovascular medicine.
DZHK scientists from Heidelberg with colleagues from München (TUM), Göttingen (DPZ), and Berlin (MDC) now identified a novel mechanism to improve arteriogenesis involving enlargement of endothelial cells, resulting in the formation of large diameter arteries in developing vascular networks. Arterial endothelial cell enlargement requires the guanine nucleotide exchange factor Trio to modulate the cytoskeleton in the endothelial cell periphery.
The authors show that Trio can be activated selectively in developing arteries by precisely titrating Vegf signaling strength in the arterial wall, which is achieved by targeting soluble Vegf receptor Flt1. Endothelial cell enlargement is a fast process, independent of shear stress or inflammatory processes and within several hours results in 2-3 fold structurally larger arterioles that can attract flow to hypoperfused regions. Due to the rapid nature of this process, the authors believe that this approach has significant advantages over the (relatively slow) conventional angiogenesis approaches aimed at improving vessel number.
Link to Paper
February 2021