Erythrocytes in the combined milieu of high glucose and high cholesterol shows glycosaminoglycan-dependent cytoadherence to extracellular matrix components

Pathological conditions are bound to affect the molecules on erythrocytes, and accordingly affect their
functions. Chondroitin sulphate/dermatan sulphate (CS/DS), one of the classes of molecules found to be
expressed in erythrocytes was previously observed by us to be either overexpressed in diabetic condition
or undergo structural changes in hypercholesterolemic condition. Both of them had implications
on their binding to extracellular matrix components (ECM). In the present work, we have explored the
quantitative changes in erythrocyte glycosaminoglycans (GAGs) and their role in erythrocyte binding
towards ECM components in the combined milieu of both diabetes and hypercholesterolemia (SFHD).
Membrane cholesterol was significantly higher in SFHD group compared to control (SFC) and diabetic
groups (SFD). Interestingly, there were no quantitative changes in CS/DS compared to SFC erythrocytes,
but showed significantly increased cytoadherence to selected ECM components to various extents. Binding
was partly dependent on CS/DS as digesting the chains resulted in relatively decreased cytoadherence.
It also showed significantly increased binding to chondroitin sulphate and heparan sulphate. Thus, combined
milieu of high glucose and high cholesterol can have more deleterious consequences than either
of them independently.