Remodelling of vascular proteoglycans of the extracelular matrix induced by human apolipoprotein A-I. Probable role in the function-cytotoxicity equilibrium.

ROSU, S. A.; CALABRESE G; BARIANDARÁN, A.; TRICERRI, M. A.; BLACHMAN, A.

Mar del Plata

Congreso; Reunión Conjunta 2016 entre la Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Farmacología Experimental (SAFE); 2016

Sociedad Argentina de Investigación Clínica (SAIC)

Apolipoprotein A-I (apoA-I) is the major constituent of human high density lipoproteins (HDL), which play a key role in reverse cholesterol transport. In addition, apoA-I exhibits antioxidant and anti-inflammatory properties and inhibit the aggregation and neurotoxicity of the amyloid- peptide. Nevertheless, wild-type apo-A-I could also be amyloidogenic, as it was associated to atherosclerosis lesions. Changes in the microenvironment have been suggested to explain protein missfolding and tissue deposition. The aim of this work was to analyze the expression and the chemical structure of proteoglycans (PGs) in human umbilical vein endothelial cells (HUVEC) in the presence of wilde type apoA-I. Recombinant apoA-I which behaved as the native protein was employed in the assays. HUVEC were cultured for 24 hs in the presence of increasing doses of apoA-I (1.5?100 µg/mL) to determine the cytotoxicity by MTT assay. After treatment, PGs were characterized through: (1) their core protein mRNA and (2) the levels of glucuronyl C-5 epimerase (DS-epi1/2) mRNA by reverse transcriptase-PCR (RT-PCR). In addition, chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) mRNA was also determined by RT-PCR. No cell cytotoxicity was determined through all the apoA-I doses analyzed. A significant decrease in biglycan and versican CS/DS PGs was detected at 1.5 µg/ml apoA-I (p