P167Dynamic course of serum-induced endothelial cell apoptosis in ST-segment elevation myocardial infarction patients treated with primary angioplasty: implications for a deregulation of immune response

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PurposeAcute loss of endothelial cells may play a role in the ischemia-reperfusion injury process. The aim of this study was to evaluate the pro-apoptotic effect of blood serum on endothelial cells in reperfused ST-segment elevation myocardial infarction (STEMI) patients.MethodsHuman umbilical vein endothelial cells (HUVEC) were incubated with serum of 20 patients with a first STEMI treated with primary angioplasty drawn before reperfusion and 24h, 96h and 30 days afterwards. Apoptosis, necrosis and viability percentages were evaluated by flow cytometry. Cytokine levels and lymphocyte subtypes were evaluated by multiplexed immunoassay and flow cytometry respectively. Values were compared with serum of 12 age- and sex- matched control subjects with normal coronary arteries. ResultsIn comparison with controls, serum of STEMI patients induced a loss of HUVEC viability mainly due to apoptosis but not necrosis. In patients, the pro-apoptotic effect of serum was maximum at 96h post-reperfusion (Figure). A pro-inflammatory response paralleled the pro-apoptotic effect of serum. In comparison with controls, at 96 hours anti-inflammatory cytokines IL-4 and IL-10 did not vary but pro-inflammatory cytokines IL-6 (p < 0.001) and IL-1β (p < 0.001) and pro-apoptotic cytokines TNF-α (p < 0.01) and TGF-β (p < 0.05) increased. Similarly a pro-inflammatory response in adaptative immune cells occurred: CD4 + cells count and Th1/Th2 ratio increased but FOXP3 + T regulatory cells count diminished (p < 0.05 in all cases). ConclusionSerum of STEMI patients induces apoptosis on endothelial cells. This effect progressively increases in the days following reperfusion and it is acompanied by an acute pro-inflammatory deregulation of the adpatative immune system.

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