# Heparan Sulfates Regulate Vascular Reactivity in Syndecan 1 Knockout Mice

## TL;DR

This study shows that heparan sulfates play a key role in regulating blood vessel function, especially in mice lacking syndecan 1.

## Contribution

The study reveals a physiological role of heparan sulfates in vascular reactivity and identifies compensatory mechanisms in knockout mice.

## Key findings

- Heparan sulfates regulate vascular reactivity to norepinephrine and acetylcholine in wild-type and Sdc1−/− mice.
- Gpc1−/− mice do not show vascular reactivity changes after heparinase III treatment.
- Knockout mice show compensatory expression of other syndecans and glypicans.

## Abstract

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 (Sdc1−/−) and glypican 1 (Gpc1−/−) 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 Sdc1−/− but not in Gpc1−/− mice. Both Sdc1−/− and Gpc1−/− showed increased compensatory expression of syndecan 2 and syndecan 4. However, while Sdc1−/− showed decreased expression of glypican 1, Gpc1−/− showed increased expression of syndecan 1 in aortic homogenates. The lack of response to the vascular reactivity effects of heparinase III in Gpc1−/− 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.