DECREASED EXPRESSION OF ETS-2 IN EPCS AS AN EARLY MARKER OF CARDIOVASCULAR INSTABILITY IN CABG PATIENTS, BENEFICIAL EFFECTS OF SITAGLIPTIN

AimIn patients with cardiovascular disease (CVD), the endothelial progenitor cells (EPCs) play a key role in endothelial repair processes. It has been hypothesized that Ets2 transcription factor could be involved in the instability of CVD/hyperlipidaemia. Recent studies have shown that the dipeptidyl peptidase‐4 (DPP‐4) is expressed on endothelial cells and appears to modulate their kinetics. Our main objective was to determine the degree of expression of transcription factor Ets2 and the endothelial repair factors Endoglin and CXCR4 in peripheral blood mononuclear cells from patients undergoing coronary artery‐bypass grafting (CABG), and to prove a possible beneficial effect of Sitagliptin.Methodsseventy patients undergoing CABG from the cardiac surgery service were selected for the study and categorized into five CVD stages. The Expression of Ets‐2, CXCR4, and Endoglin were measured by Western blot. Sitagliptin effect on EPCs and on the expression of different factors was studied by Western blot, ELISA and immunofluorescence. This study was conducted according to the World Medical Association Declaration of Helsinki and informed consent was obtained from all subjects before sampling.Resultsan increase in the expression of the transcription factor Ets‐2 in patients, without CV predictor risk factor associated with early stages of CV instability was observed (GI: 2.16 ± 1.4). Ets‐2 expression decreased in patients with longer evolution of CVD (GII: 1.16±0.8; GIII1.06±0.5; GIV: 0.91±0.3; GV: 0.56±0.3). A direct association of expression of Ets‐2 with age (p=0.04) and Endoglin expression (p=0.008), and indirectly with the evolution of CVD (p=0.008) and hyperlipidaemia (p=0.03) was found. A direct effect of Sitagliptin 1μM on the colony formation of EPCs at 6 and 12 hours (p=0.0077) and on expression of CXCR at 24 hours (p=0.0201) and SDF1 at 6 and 24 hours (p=0.0085) was observed.ConclusionsThe transcription factor Ets‐2 could be an early marker of cardiovascular instability associated with states of hyperlipidaemia. Our data suggest that a poor functionality of circulating EPCs could be associated with decreased expression of the transcription factor Ets‐2 in advanced stages of cardiovascular disease. Sitagliptin treatment of cultured EPCs, could help to revert EPCs deficient functionality. Therefore, the activatory response might depend on the SDF1‐CXCR4 axis.Support or Funding InformationFIS PI12/00590. Convocatoria CONACYT‐Gobierno del Estado de San Luis Potosí‐México 2012.