Background:The mechanisms by which the PECAM-1⅐G␣ q/11 mechanosensitive complex mediates endothelial flow responses remain unclear. Results: The PECAM-1⅐G␣ q/11 complex contains heparan sulfate proteoglycans (HSPGs) and is disrupted by inhibition of HS. Conclusion:The interaction between PECAM-1 and G␣ q/11 may be mediated by the HS of the HSPG syndecan-1. Significance: Targeting specific HSPGs may be an effective strategy for the therapeutic treatment of vascular diseases.