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

## TL;DR

Endothelial cells use actomyosin bundles anchored by CCM1 to contract and control blood vessel size during development.

## Contribution

The study identifies circumferential actomyosin bundles and CCM1 as key drivers of endothelial cell contraction and vessel diameter regulation.

## Key findings

- Circumferential actomyosin bundles in endothelial cells drive contraction and vessel constriction.
- Loss of CCM1 disrupts actin bundle anchoring, leading to vessel dilation and malformations.
- Endothelial cell number and shape changes are coordinated to regulate vessel diameter.

## Abstract

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.

Dysregulation of blood vessel size can cause vascular malformations. Here, the authors demonstrate that endothelial cells generate circumferential actomyosin cables to control the size of cells and vessels.