Prevention of endothelial cell apoptosis induced by neutrophils and sera from patients with acute myocardial infarction

Apoptosis of cardiomyocytes and vascular endothelial cells has been shown to contribute to disease progression in coronary atherosclerosis, in myocardial infarction and in ischemia-reperfusion injury. Sera were obtained from 13 patients with acute ST elevation myocardial infarction and successful primary percutaneous coronary intervention. Human umbilical venous endothelial cells (HUVECs) were incubated with sera from these patients with or without addition of neutrophil granulocytes. TUNEL staining was performed, and apoptotic cells were quantified with immunofluorescence microscopy. To reduce apoptotic damage, ascorbic acid, vitamin E, ulinastatin, or activated protein C were added to patients' sera, with or without neutrophils, before incubation with endothelial cells. Incubation of endothelial cells with sera from patients increased the apoptosis rate significantly, compared to sera from 7 healthy controls (p < 0.001). Co-incubation of endothelial cells with patients' sera and neutrophils led to a further significant increase of apoptosis. The addition of ascorbic acid, vitamin E, or activated protein C significantly decreased apoptosis rates of endothelial cells in the presence of neutrophils in vitro. Antiapoptotic strategies may be relevant for the therapy of acute coronary syndromes, since elevated leukocyte counts have been shown to be associated with increased morbidity and mortality in coronary heart disease.