Heparan Sulfates Regulate Vascular Reactivity in Syndecan 1 Knockout Mice

Heparan sulfates (HS) are polysaccharides abundantly expressed in the extracellular matrix and the glycocalyx of endothelial cells, having a putative role in vascular function. The role of HS in vascular reactivity remains unclear. Herein, we sought to determine whether HS regulate the vascular tone in physiological conditions. Using male, 6-8-weeks-old, CD1, C57BL/6, syndecan 1 (<i>Sdc1^-/-</i>) and glypican 1 (<i>Gpc1^-/-</i>) knockout mice, we investigated if the degradation of HS with heparinase III altered vascular reactivity to norepinephrine (NE), acetylcholine (ACh) and potassium chloride (KCl). Our findings indicate that HS are crucial players in the vascular response to NE and ACh in CD1, C57BL/6, and <i>Sdc1^-/-</i> but not in <i>Gpc1^-/-</i> mice. Both <i>Sdc1^-/-</i> and <i>Gpc1^-/-</i> showed increased compensatory expression of syndecan 2 and syndecan 4. However, while <i>Sdc1^-/-</i> showed decreased expression of glypican 1, <i>Gpc1^-/-</i> showed increased expression of syndecan 1 in aortic homogenates. The lack of response to the vascular reactivity effects of heparinase III in <i>Gpc1^-/-</i> suggests a differential role of HS to proteoglycan function in the regulation of the vascular tone. Our data demonstrate a physiological role for HS in the regulation of the vascular tone in physiological conditions.