Abstract：
Endothelial cells lining the blood vessel wall communicate intricately with the surrounding extracellular matrix, translating mechanical cues into biochemical signals. Moreover, vessels require the capability to enzymatically degrade the matrix surrounding them, to facilitate vascular expansion. c-Src plays a key role in blood vessel growth, with its loss in the endothelium reducing vessel sprouting and focal adhesion signalling. Here, we show that constitutive activation of c-Src in endothelial cells results in rapid vascular expansion, operating independently of growth factor stimulation or fluid shear stress forces. This is driven by an increase in focal adhesion signalling and size, with enhancement of localised secretion of matrix metalloproteinases responsible for extracellular matrix remodelling. Inhibition of matrix metalloproteinase activity results in a robust rescue of the vascular expansion elicited by heightened c-Src activity. This supports the premise that moderating focal adhesion-related events and matrix degradation can counteract abnormal vascular expansion, with implications for pathologies driven by unusual vascular morphologies.
摘要：
血管壁内的内皮细胞与周围的细胞外基质错综复杂地沟通，将机械线索转化为生化信号。此外，血管需要酶降解周围基质的能力，以促进血管扩张。c-Src在血管生长中起关键作用，其在内皮中的损失减少了血管发芽和局灶性粘附信号。这里,我们显示内皮细胞中c-Src的组成型激活导致血管快速扩张，独立于生长因子刺激或流体剪切应力。这是由局灶性粘附信号和大小的增加驱动的，增强了负责细胞外基质重塑的基质金属蛋白酶的局部分泌。基质金属蛋白酶活性的抑制导致由提高的c-Src活性引起的血管扩张的有力挽救。这支持了一个前提，即缓和局灶性粘连相关事件和基质降解可以抵消异常血管扩张，与异常血管形态驱动的病理有关。
