Atheroprone fluid shear stress-regulated ALK1-Endoglin-SMAD signaling originates from early endosomes.

ABSTRACT:

Background

Fluid shear stress enhances endothelial SMAD1/5 signaling via the BMP9-bound ALK1 receptor complex supported by the co-receptor Endoglin. While moderate SMAD1/5 activation is required to maintain endothelial quiescence, excessive SMAD1/5 signaling promotes endothelial dysfunction. Increased BMP signaling participates in endothelial-to-mesenchymal transition and inflammation culminating in vascular diseases such as atherosclerosis. While the function of Endoglin has so far been described under picomolar concentrations of BMP9 and short-term shear application, we investigated Endoglin under physiological BMP9 and long-term pathophysiological shear conditions.

Results

We report here that knock-down of Endoglin leads to exacerbated SMAD1/5 phosphorylation and atheropr

SUBMITTER: Mendez PL 

PROVIDER: S-EPMC9520843 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature