Abstract 5901: Cardiac Expression of CCN1, Capable of Promoting Adhesion of CD34+ Progenitor Cells, Is Strongly Induced in Parvovirus B19-Associated Cardiomyopathy
The clinical phenotype of human dilated cardiomyopathy (DCM) encompasses a broad spectrum of etiologically distinct disorders. We obtained the cardiac expression profile of a DCM subtype (DCMi-B19) characterized by cardiac inflammation and parvovirus B19 (B19) persistence, to identify possible new therapeutic targets in humans. By microarray analysis and TaqMan PCR endomyocardial biopsies from DCMi-P19 patients (n=8) were compared to controls w/o cardiac disease. In DCMi-B19 an expression profile with dysbalance between several gene regulatory networks was observed. Tab. 1/2 classify deregulated genes in a group closely correlated (p<0.01) with left ventricular ejection fraction (EF) and another one w/o correlation to EF. CCN1 was the most strongly upregulated of the EF-independent genes which encompass further members of the CCN1 regulatory network including CCN2=CTGF. In contrast the genes in tab. 2 are closely EF-correlated. We have previously shown that CCN1 is induced in endothelial cells by pro-inflammatory cytokines in vitro, which may also be the mechanism of its induction in human DCMi-B19 hearts. Two recent studies described the potential of CCN1 to promote migration/adhesion of CD34+ stem cells, and of activated monocytes via alphaMbeta2 integrin. This suggests that the CCN1 induction in DCMi-B19 may influence the influx of CD34+ stem cells and activated monocytes to the inflamed heart, and obviously this may occur independent of hemodynamic impairment. B19 viruses infect cardiac microvascular endothelium, and endothelial CCN1 induction may therefore be involved in disease pathogenesis by altering circulating cell interactions with the inflamed heart.