Low-flow intussusception and metastable VEGFR2 signaling launch angiogenesis in ischemic muscle.

ABSTRACT: Efforts to promote sprouting angiogenesis in skeletal muscles of individuals with peripheral artery disease have not been clinically successful. We discovered that, contrary to the prevailing view, angiogenesis following ischemic muscle injury in mice was not driven by endothelial sprouting. Instead, real-time imaging revealed the emergence of wide-caliber, primordial conduits with ultralow flow that rapidly transformed into a hierarchical neocirculation by transluminal bridging and intussusception. This process was accelerated by inhibiting vascular endothelial growth factor receptor-2 (VEGFR2). We probed this response by developing the first live-cell model of transluminal endothelial bridging using microfluidics. Endothelial cells subjected to ultralow shear stress could reposition insi

SUBMITTER: Arpino JM 

PROVIDER: S-EPMC8626079 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature