Abstract 5633: Endothelial Progenitor Cells - A Troian Horse in Systemic Endothelial Damage in Patients With Cardiac Parvovirus B19?
Detection of the vasculotropic parvovirus B19 (B19V) in endomyocardial biopsies (EMB) is strongly associated with endothelial dysfunction and coronary vasospasms mimicking acute myocardial infarction. B19V replicates primarily in erythroblasts in bone marrow (BM). Endothelial progenitors (EPC) mobilised from BM participate in endothelial cell (EC) regeneration. We, therefore, tested the hypothesis of a systemic EC damage with a direct influence of B19V on EPC and endothelial regeneration. Circulating apoptotic mature endothelial cells (CMAEC; CD45−CD146+vWF+Ann+) and CD45dimCD34+KDR+-EPC were quantified from blood by FACS analysis. In 12 patients with B19V (>500 copies/μg DNA) in EMB, numbers of CMAEC (27±12.8/μl) were 6fold higher compared to 9 healthy controls (p<0.05). There were no transcoronary gradients (TCG) of CMAEC, in contrast (p<0.05) to patients with troponin T negative acute coronary syndromes (n=11; +150%; p<0.05), pointing to a systemically induced EC damage. EPC were significantly higher in patients with B19V compared to controls (0.24±0.1%/PMNC vs. 0.008±0.001%/PMNC; p<0.05). In contrast, EPC-function (CFU-Hill) was reduced in these patients (p<0.05). There was a strong trend towards a negative TCG (−33%±40%, p=0.051) of EPC. Intracardiac SDF-1α mRNA was 4.6-fold (p<0.05) and CXCR4 mRNA was twofold (p<0.05) increased in B19V+-patients compared to controls, further supporting the hypothesis of a continuous homing. In a second study, CD34+KDR+-EPC of these patients (n=7) were magnetically separated from BM and blood and B19V DNA with qPCR compared to 5 controls. Compared to controls, only patients had B19V DNA in BM and blood (21399±10378 vs. 16±12 copies/ug DNA in CD34−, p<0.05) and documenting replication intermediates of B19V, mRNA was detected in CD34+KDR+-EPC (4 – 1435 copies cDNA/μg DNA) in BM and blood. Indeed, in one patient with highest copy numbers of B19V mRNA in CD34+KDR+ in blood, B19V mRNA was detected in EMB. Thus, for the first time we present a virally-induced systemic endothelial damage and B19V infection in EPC with replication intermediates. Continuous circulation of BM-derived, B19V-infected EPC could contribute to impaired endothelial regeneration.