Action of modified erythropoietins on endothelial cells in a proinflammatory environment

CHAMORRO, ME; SCHIAVINATO, D; MALTANERI, R; SHIAPPACASSE, A; NESSE, A; VITTORI, D

Mar del Plata

Congreso; LXII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2017

Erythropoietin (Epo), the erythropoiesis growth factor, is also known as an antiapoptotic agent. In this context, carbamylated Epo (cEpo) maintains the neuroprotective effect but fails to stimulate erythropoiesis. Despite the benefit of Epo treatment to overcome anemia associated to different pathologies, a significant number of patients, particularly those with cardiovascular or chronic renal diseases, fail to respond. This may be related to the simultaneous presence of other independent risk factors, such as hyperhomocysteinemia. This study was aimed at identifying Epo structural changes due to carbamylation and N-homocysteinylation, and investigating whether these changes could affect Epo activity on EA.hy926 endothelial cells in a proinflammatory environment. cEpo was prepared by reaction with potassium cyanate while homocysteine thiolactone was incubated with Epo to yield the N-homocysteinylated protein. Analysis by gel and capillary electrophoresis revealed structural changes with respect to the native protein. Wound healing assays showed a stimulatory effect of TNF-α on cell migration which was significantly increased by TNF-α+Epo combination (C 21±2%, *TNF-α 44±3%, Epo 30±2%, *EpoTNF-α 66±4%, *P