Interaction of apolipoprotein A-I variants with synthetic polymeric matrices that mimic an extracellular matrix

BARANDIARAN, ALDANA; TOLEDO, LEANDRO; URBANO, BRUNO; CALABRESE, GRACIELA C.; ROSU SILVANA A.; SANCHEZ DONOSO SUSANA; M. A. TRICERRI

La Plata

Congreso; XLVII Reunión Anual de la Sociedad Argentina de Biofísica; 2018

Sociedad Argentina de Biofísica

Specific interactions of apolipoproteins with components of the extracellular matrix, particularly proteoglycans (PGs), have been postulated to play a key role regulating events associated to atherosclerosis. Modification of these interactions seems to be dependent on age, cellular differentiation, and pathological conditions. The mechanism behind these modifications has been reported to be centered on the expression of glycosaminoglycans (GAGs) with different length, position of sulfate substitution and composition. Human apolipoprotein A-I (apoA-I Wt) under physiological conditions does not bind GAGs, but our results interestingly show that ApoA-I Arg173Pro (a natural mutant involved in cardiac amyloidosis) forms heparin/protein complexes at pH 7.4 with higher efficiency than the Wt1. These results indicate that electrostatic interactions could play a key role in the interaction of apo A-I with the extracellular matrix (ECM). In order to further study the specific role of the matrix?s charge on the interaction of apoA-I with GAGs, we synthesized polymers having different ratios of sulfated or hydroxilated monomers (sodium 4-styrene sulfonate (SSNa) and 2-hydroxyethyl methacrylate (HEMA)) and studied the binding of apoA-I Wt or Arg173Pro, both fluorescently labeled.Our results indicate that both proteins are highly retained as long as the negative charge increases, and in addition it was shown that the mutant is more retained than the Wt, indicating that the retention of specific proteins in the ECM could be part of the pathogenicity.We concluded that charge and chemical composition of the ECM could mediate apoA-I binding to GAGs and as a consequence alter the delicate equilibrium of protein and function.1 Rosu, S.A., Rimoldi, O.J., Prieto, E.D. et al. PLoS One 2015; 10: e0124946.AcknowledgementsAuthors acknowledge fundings of ANPCyT (PICT 2016-0849) and UNLP (M187)