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Riesinger, Lisa; Saemisch, Michael; Nickmann, Markus and Methe, Heiko (2018): CD34(+) circulating cells display signs of immune activation in patients with acute coronary syndrome. In: Heart and Vessels, Vol. 33, No. 12: pp. 1559-1569

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Bone marrow-derived endothelial progenitor cells (EPC) are released into the peripheral blood in situations of vascular repair/angiogenesis. Regulation of vascular repair and angiogenesis by EPC depends not only on the number of circulating EPC but also on their functionality. As endothelial cells can act as antigen-presenting cells in coronary artery disease (CAD), we postulated that EPC can be immune activated here as well. CD34(+)-EPC were isolated from peripheral blood of patients with ST-elevation myocardial infarction (STEMI, n=12), non-STEMI/unstable angina (UA, n=15), and stable CAD (SA, n=18). Expression of HLA-DR, adhesion and costimulatory molecules by isolated CD34(+)-EPC were compared with levels in healthy controls (n=18). There were no significant differences in VCAM-1 and CD80 expression by peripheral circulating CD34(+)-EPC between the four groups, yet expression of CD86 was highest in UA (p<0.05). ICAM-1 expression was lowest in SA (p<0.01). CD34(+)-EPC constitutively expressed HLA-DR across all groups. Of note, patients pretreated with HMG-CoA reductase inhibitors exhibited lower expression of VCAM-1 by CD34(+)-EPC throughout all patient groups;furthermore, statins significantly limited ex vivo-induced upregulation of ICAM-1 by TNF-alpha. To the best of our knowledge, this is the first study to examine the expression of immune markers in peripheral circulating CD34(+)-EPC ex vivo. We demonstrate that CD34(+)-EPC display different patterns of adhesion and costimulatory molecules in various states of CAD. Expression levels were affected by pretreatment with statins. Hence, immune activity of peripheral circulating CD34(+) cells might play a pathophysiologic role in evolution of CAD.

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