Implications of naturally occurring variations in arterial glycosaminoglycans for the pathogenesis of atherosclerosis

RESUMO

Proteoglycans and their constituent glycosaminoglycan (GAG) side chains participate in the pathogenesis of atherosclerosis by holding and modifying plasma lipoproteins (LDL). Of the GAGs existing in arteries, only chondroitin sulfate and dermatan sulfate interact with LDL.In addition, these LDL-binding GAGs show some naturally occurring variations that have direct consequences to their participation in atherogenesis. These variations are: (1) Polydispersity: GAGs normally vary widely in molecular weight and in human aortas there are longer chains of chondroitin sulfate/dermatan sulfate presenting stronger affinity to LDL; (2) Ageing: steric factors play a role in GAG-LDL interaction, and with ageing there is an increase in the relative content of the 6-sulfated isomer of aortic chondroitin sulfate; this isomer binds to LDL, whereas the 4-sulfated isomer does not: (3) Anatomic heterogeneity: The risk to develop atherosclerotic lesions is different among arteries, and the composition and LDL binding affinity of chondroitin sulfate/dermatan sulfate from normal arteries correlate with their susceptibility to atherosclerosis. The participation of GAGs in atherosclerosis should therefore be viewed as variable.