Proteoglycan 4 (lubricin) is a highly sialylated glycoprotein associated with cardiac valve damage in animal models of infective endocarditis

Streptococcus gordonii and Streptococcus sanguinis are primary colonizers
of tooth surfaces and are generally associated with oral health, but can
also cause infective endocarditis (IE). These species express
“Siglec-like” adhesins that bind sialylated glycans on host glycoproteins,
which can aid the formation of infected platelet–fibrin thrombi
(vegetations) on cardiac valve surfaces. We previously determined that the
ability of S. gordonii to bind sialyl T-antigen (sTa) increased
pathogenicity, relative to recognition of sialylated core 2 O-glycan
structures, in an animal model of IE. However, it is unclear when and
where the sTa structure is displayed, and which sTa-modified host factors
promote valve colonization. In this study, we identified sialylated
glycoproteins in the aortic valve vegetations and plasma of rat and rabbit
models of this disease. Glycoproteins that display sTa vs. core 2 O-glycan
structures were identified by using recombinant forms of the streptococcal
Siglec-like adhesins for lectin blotting and affinity capture, and the
O-linked glycans were profiled by mass spectrometry. Proteoglycan 4
(PRG4), also known as lubricin, was a major carrier of sTa in the infected
vegetations. Moreover, plasma PRG4 levels were significantly higher in
animals with damaged or infected valves, as compared with healthy animals.
The combined results demonstrate that, in addition to platelet GPIbα, PRG4
is a highly sialylated mucin-like glycoprotein found in aortic valve
vegetations and may contribute to the persistence of oral streptococci in
this protected endovascular niche. Moreover, plasma PRG4 could serve as a
biomarker for endocardial injury and infection.