Phosphatidylserine feeding reduces the presence of glycocalyx components glypican-1 and CD44 in the aortic wall of diabetic mice

The vascular glycocalyx, in particular, that which protrudes from the endothelium into the vascular lumen, is an important player in multiple functions of blood vessels. The glycocalyx is a mesh of glycoproteins and proteoglycans present on the outer layer of the cellular plasmalemma. In endothelial cells, the glycocalyx participates in the process of mechanotransduction that converts shear stress forces generated by the flow of blood into intracellular signals that produce functional molecules such as the potent vasodilator, nitric oxide. The glycocalyx is in a constant remodeling process of degradation and synthesis. A major participant in its degradation is a disintegrin and metalloproteinase-17 (ADAM17), a proteolytic cell-anchored enzyme that sheds diverse components of the glycocalyx from the cell surface. ADAM17 is also a proinflammatory enzyme that is upregulated in multiple disease conditions including obesity and diabetes. As the endothelial glycocalyx has been shown to be reduced in such conditions, we hypothesized that ADAM17 inhibition would increase the presence of vascular glycocalyx structures in diabetes. To test this hypothesis while improving the translatability of our study, we fed the dietary supplement and competitive inhibitor of ADAM17, phosphatidylserine, to 9-week-old diabetic db/db mice (n=10) for 4 weeks. Peanut butter vehicle control was fed to 10 db/db mice and an additional 10 wild-type untreated mice served as reference controls. All differences reported here are significant at P<0.05. Contrary to our expectations, neither plasma ADAM17 activity nor its presence in the aortic wall was different between db/db mice vs wild-types or between phosphatidylserine-treated vs. untreated db/db mice. Immunohistochemistry analyses of aortic samples further indicated that compared to wild-types, db/db mice had increased presence of the glycocalyx components glypican-1 and CD44 and that these glycocalyx components were lesser in aortas from db/db mice treated with phosphatidylserine than in those from db/db mice fed vehicle. As for the presence of the major extracellular matrices collagen and elastin, treatment with phosphatidylserine reduced collagen-to-elastin ratios in the aortas of db/db mice. All these results suggest that dietary supplementation with phosphatidylserine decreases the expression of arterial glycocalyx components in diabetic mice. The implications of these specific vascular structural changes on cardiovascular pathophysiology remain to be fully elucidated. National Institutes of Health grant: R01HL153264 to LM-L and JP This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.