Vascular chondroitin/dermatan sulfate proteoglycans remodeling induced by Apo A- I and natural variants. Probable role in settlement of amyloidosis.

BIROCCO, AM; CALABRESE, GRACIELA C.; EIGUREN, AC; ROSU SILVANA A.; FUNEZ, F; M. A. TRICERRI

Manchester

Congreso; Matriz Biology Europe 2018; 2018

Federation of European Connective Tissue Societies

Amyloidosis constitutes a heterogeneous group of diseases involving protein misfolding and deposition of fibrils. Apolipoprotein A-I (apoA-I), the main protein of plasma high-density lipoproteins (HDL), removes excess cell cholesterol and protects against atherosclerosis. Nevertheless, some natural variants (R173P) or their N-terminal fragments (IOWA, N-terminal peptide of G26R) of the native protein with structural disorder elicit their propensity to suffer misfolding or aggregation. Moreover, amyloidosis due to the protein with the native sequence has been described as diffuse protein aggregates in atherosclerotic plaques. Our previous reports suggest that specific interactions of ApoA-I with glycosaminoglycans could elicit its retention and/or aggregation. Furthermore, recent studies indicate that protein cores of proteoglycans (PGs) may influence the type and modification patterns of the subsequently attached glycosaminoglycan chains. We hypothesize that mutations in human Apo A-I may affect the core protein pattern expression of vascular chondroitin/dermatan sulfate PGs, modulating chemical changes in the glycosylation pattern which elicit extracellular ApoA-I aggregation.