The clinical phenotype of human dilated cardiomyopathy (DCM) encompasses a broad spectrum of etiologically distinct disorders. As targeting of etiologyrelated pathogenic pathways may be more efficient than current standard heart failure treatment, we obtained the genomic expression profile of a DCM subtype characterized by cardiac inflammation to identify possible new therapeutic targets in humans. In this inflammatory cardiomyopathy (DCMi), a distinctive cardiac expression pattern not described in any previous study of cardiac disorders was observed. Two significantly altered gene networks of particular interest and possible interdependence centered around the cysteine-rich angiogenic inducer 61 (CYR61) and adiponectin (APN) gene. CYR61 overexpression, as in human DCMi hearts in situ, was similarly induced by inflammatory cytokines in vascular endothelial cells in vitro. APN was strongly downregulated in DCMi hearts and completely abolished cytokine-dependent CYR61 induction in vitro. Dysbalance between the CYR61 and APN networks may play a pathogenic role in DCMi and contain novel therapeutic targets. Multiple immune cellassociated genes were also deregulated (e.g., chemokine ligand 14, interleukin-17D, nuclear factors of activated T
These data indicate the existence of a local cardiac adiponectin system regulated independent of adiponectin and TNFalpha serum levels and its disturbance in cardiac pathology. The study suggests a role for adiponectin in the pathogenesis of DCM and implicates the adipocytokine as a possible future therapeutic target in DCM.
We report on a rare case of a late-onset drug-induced lupus erythematosus. A 35 year old male patient complained about dyspnea, chest pain and reduced physical activity for three months. His medical history consisted of epilepsy treated with carbamazepine for 20 years. After diagnosis of a large pericardial effusion and percardiocentesis (1200 ml) the diagnosis of viral perimyocarditis was suspected. Under antiphlogistic treatment the symptoms vanished initially. Four weeks later the pericardial effusion recurred and a livedo reticularis became evident. A structural or infectious heart disease, in particular viral myocarditis, was ruled out invasively. Serologic testing revealed antinuclear antibodies and antibodies against histones without presence of antibody against ds-DNA, thereby confirming the diagnosis of carbamazepine-induced lupus erythematodes. After discontinuation of carbamazepine and immunosuppressive medication the patient recovered completely.
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.
Table 1:
EF-Independent Gene Deregulation
Table 2:
EF-Correlated Gene Deregulation
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