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<p>Blood vessels undergo extensive remodelling to acquire appropriate diameters, yet how endothelial cells coordinate changes in their number and shape to achieve this remains unclear. Here we show that endothelial cell contraction and rearrangements underlie the inverse relationship between cell number and vessel diameter during development. Using high-resolution imaging and manipulation of actin cytoskeleton organisation, in vivo laser ablation experiments and mathematical simulations, we reveal that tension-bearing, circumferential actomyosin bundles form in the endothelial cortex to drive endothelial cell contraction and vessel constriction. The anchorage of circumferential actin bundles to cell-cell junctions is mediated by Ccm1/Krit1 protein. Importantly, the loss of circumferential actin bundles in <i>ccm1</i>-deficient endothelial cells causes cell enlargement and impaired vessel constriction, culminating in vessel dilation characteristic of cerebral cavernous malformations. Our multiscale study demonstrates how circumferential actomyosin-driven endothelial cell contractions regulate vessel diameter and provides insights into mechanisms of both normal vascular development and disease pathogenesis.</p>

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Circumferential actomyosin bundles anchored by CCM1 drive endothelial cell contraction and vessel constriction

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月27日

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  • Yan Chen,
  • Nuria Taberner,
  • Jason da Silva,
  • Vivek Semwal,
  • Biplab Bhattacherjee,
  • Julia Eckert,
  • Igor Kondrychyn,
  • Mingzhao Hu,
  • Nitish Aswani,
  • Guihua Chen,
  • Yasushi Okada,
  • Anne Karine Lagendijk,
  • Tatsuo Shibata,
  • Satoru Okuda,
  • Li-Kun Phng

摘要

Blood vessels undergo extensive remodelling to acquire appropriate diameters, yet how endothelial cells coordinate changes in their number and shape to achieve this remains unclear. Here we show that endothelial cell contraction and rearrangements underlie the inverse relationship between cell number and vessel diameter during development. Using high-resolution imaging and manipulation of actin cytoskeleton organisation, in vivo laser ablation experiments and mathematical simulations, we reveal that tension-bearing, circumferential actomyosin bundles form in the endothelial cortex to drive endothelial cell contraction and vessel constriction. The anchorage of circumferential actin bundles to cell-cell junctions is mediated by Ccm1/Krit1 protein. Importantly, the loss of circumferential actin bundles in ccm1-deficient endothelial cells causes cell enlargement and impaired vessel constriction, culminating in vessel dilation characteristic of cerebral cavernous malformations. Our multiscale study demonstrates how circumferential actomyosin-driven endothelial cell contractions regulate vessel diameter and provides insights into mechanisms of both normal vascular development and disease pathogenesis.