Vascular Remodeling in Salivary Glands with Sjögren’s Syndrome

Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disorder that causes secretory dysfunction in the salivary and lacrimal glands. SS is characterized by extensive lymphocytic infiltration into the salivary glands that is associated with decreased of saliva secretion. During the evolution of chronic inflammation, blood vessels have been shown to proliferate, enlarge, and sprout in response to pro-inflammatory mediators. This vascular remodeling is largely mediated by VEGF-A and its receptor VEGFR2 which are potent inducers of blood vessel growth. Remodeling of the blood vessels has implications for saliva secretion, as it can result in changes to the physiological forces that mediate secretion. Despite these potential effects, very little is known about the role or degree of angiogenesis in SS.

Objectives: Our goal was to expand on previous studies and determine the degree and localization of the vascular changes in human minor salivary glands from patients with SS. Furthermore, we studied whether similar changes also occur in submandibular glands of the SS mouse model, NOD/ShiLtJ.

Methods: For these studies, salivary gland tissue sections were stained with markers for endothelial cells (PECAM-1 and VE-cadherin). Markers for endothelial cell proliferation (VEGF and VEGFR-2) were quantified by western blot analyses.

Results: Our results indicate that human minor salivary glands with SS show an increase in blood vessel coverage area when compared to control glands. However, NOD/ShiLtJ mice do not show a similar increase in blood vessel coverage as compared to the C57BL/6 control mice.

Conclusions: These results help us understand the physiological importance of blood vessel remodeling during the progression of SS, especially as it relates to lymphocytic trafficking and saliva secretion. These studies also allow us to evaluate pre-clinical models for evaluation of novel treatments, especially those targeting blood vessels.