Abstract 13097: Impaired Endothelial Regeneration by Human Parvovirus B19 is Associated with a Disrupted SDF-1/CXCR4 Axis
B19V is associated with endothelial dysfunction and cardiomyopathy. We previously showed induction of apoptosis after infection of circulating angiogenic cells (CAC) with B19V and impaired endothelial regeneration in vivo despite increased numbers of CAC. We thus tested the hypothesis of a disrupted SDF-1/CXCR4 axis, essential for CAC trafficking in symptomatic chronic B19V-cardiomyopathy. Patients with chronic B19V-cardiomyopathy (n=19) had significantly reduced expression of surface CXCR4 on circulating CD34+KDR+ cells (-70%, p<0.05) compared to controls (n=16) despite increased numbers of circulating CD133+KDR+ (2.9-fold, p<0.005) and CD45dimCD34+KDR+ (2.1-fold, p<0.05) measured by FACS from peripheral blood. Contrasting to controls (p<0.05), numbers of circulating CD45dimCD34+KDR+-PC showed a significant reduction (-47%, p<0.05) after transcardiac passage in B19V patients. Increased serum SDF-1α and SDF-1α mRNA from endomyocardial biopsies (EMB) in patients with B19V compared to controls (both p<0.05) and the strong correlation of SDF-1α mRNA with HIF-1α mRNA (r = 0.51, p< 0.05) indicated ischaemia triggered mobilisation causing increased CAC. Reduced migratory function (p<0.05) of eo-EPC from B19V patients compared to controls underlines this finding. Reduced numbers of resident cardiac stem cells (ckit+CD45-)from EMB (3.4-fold, p<0.05) indicate impaired cardiac regeneration in B19V cardiomyopathy. In contrast to chronic B19V infection, increased intracellular and extracellular CXCR4 (4.5-fold and 6-fold, p<0.05) were detected in freshly in vitro B19V infected eo-EPC, without increased migratory capacity. Currently, a gene array is performed to further dissect genes involved in B19V modulated CAC trafficking. In conclusion, we for the first time report B19V interfering with trafficking of target cells. Patients with B19V cardiomyopathy present a disruption of the SDF-1/CXCR4 axis. Despite a cardiac increase of the homing and mobilising factor SDF-1α in B19V, reduced expression of CXCR4 may account for the reduced angiogenic potential of CAC further promoting secondary organ damage.
- © 2012 by American Heart Association, Inc.