Asymmetric dimethylarginine (ADMA) inhibits the effect of erythropoietin on endothelial cell

SCHIAPPACASSE AGUSTINA; CHAMORRO MARÍA EUGENIA; NESSE ALCIRA; MALTANERI ROMINA EUGENIA; VITTORI DANIELA

Congreso; LXIV Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2019

Hyperhomocysteinemia induces vascular endothelial dysfunction, an early hallmark of atherogenesis. Previously, we found a sensitizing effect of the inflammatory cytokine TNF-alpha on a promigratory action of erythropoietin (Epo), which was not observed when the molecule was modified by N-homocysteinylation with homocysteine thiolactone, the reactive derivative of homocysteine. The strong correlation found between hyperhomocysteinemia and levels of asymmetric dimethylarginine (ADMA), the amino acid formed during methylation of proteins, has been considered of interest in endothelial dysfunction. Therefore, the aim of this work was to study whether ADMA accumulation could affect the ability of different factors to induce endothelial cell migration. Wound healing assays of EA.hy926 endothelial cells stimulated by 10% fetal bovine serum (FBS), 20 ng/mL VEGF or Epo+TNF-alpha (80 ng/mL and 30 ng/mL, respectively) were performed in the presence or absence of ADMA (30 or 100 µM). Results are expressed as a percentage of the cell migration obtained in the presence of FBS. FBS: 100; Control: 22.0±2.4; ADMA: 20.1±3.4; *FBS+ADMA30: 66.6±3.5; **FBS+ADMA100: 43.3±3.9; Epo+TNF-alpha: 56.4±1.2; *Epo+TNF-alpha+ADMA30: 37.4±2.9; **Epo+TNF-alpha+ADMA100: 31.1±1.6; VEGF: 44.5±2.9; *VEGF+ADMA30: 30.3±2.1; **VEGF+ADMA100: 19.6±2.8; *P