Among the three nonmuscle myosin 2 (NM2) paralogs, NM 2A and 2B, but not 2C, are detected in endothelial cells. To study the role of NM2 in vascular formation, we ablate NM2 in endothelial cells in mice. Ablating NM2A, but not NM2B, results in reduced blood vessel coverage and increased vascular branching in the developing mouse skin and coronary vasculature. NM2B becomes essential for vascular formation when NM2A expression is limited. Mice ablated for NM2B and one allele of NM2A develop vascular abnormalities similar to those in NM2A ablated mice. Using the embryoid body angiogenic sprouting assay in collagen gels reveals that NM2A is required for persistent angiogenic sprouting by stabilizing the endothelial cell cortex, and thereby preventing excessive branching and ensuring persistent migration of the endothelial sprouts. Mechanistically, NM2 promotes focal adhesion formation and cortical protrusion retraction during angiogenic sprouting. Further studies demonstrate the critical role of Rho kinase–activated NM2 signaling in the regulation of angiogenic sprouting in vitro and in vivo.

在三个非肌肉肌球蛋白2（NM2）旁系同源物中，在内皮细胞中检测到NM 2A和2B，但未检出2C。为了研究NM2在血管形成中的作用，我们在小鼠内皮细胞中消融NM2。消融NM2A（而不是NM2B）会导致血管覆盖面积减少，并在发育中的小鼠皮肤和冠状血管中增加血管分支。当NM2A表达受到限制时，NM2B对于血管形成至关重要。NM2B消融的小鼠和NM2A的一个等位基因发生血管异常，类似于NM2A消融的小鼠。在胶原蛋白凝胶中使用胚状体血管新生芽试验表明，NM2A通过稳定内皮细胞皮层，从而防止过度分支并确保内皮芽的持久迁移，来持续进行血管新生。机械上，NM2促进血管生成发芽过程中的粘着斑形成和皮质突出回缩。进一步的研究表明，在体内外，Rho激酶激活的NM2信号在调节血管新生方面起着关键作用。