Atrial natriuretic peptide and CD34 overexpression in human idiopathic dilated cardiomyopathies

Abstract

Idiopathic dilated cardiomyopathy (IDCM) is a primary myocardial disease of unknown cause characterized by ventricular chamber enlargement with impaired contractile function. In familial forms of IDCM, mutations of genes coding for cytoskeletal proteins related to force transmission, such as dystrophin, cardiac actin, desmin, and delta-sarcoglycan, have been identified. Here, we report the data of a retrospective investigation carried out to evaluate the expression of atrial natriuretic peptide (ANP), CD34, troponin T and nestin in the myocardium of patients affected with IDCM. Formalin-fixed and paraffin-embedded consecutive tissue sections from the ventricular wall of 10 human normal hearts (NH) following forensic autopsy and 22 IDCM (living explanted hearts) were studied using primary monoclonal antibodies against ANP, CD34, troponin T and nestin by immunohistochemistry. Myocardial fibers were counted independently by three pathologists. Statistics included analysis of variance, log-rank test for Kaplan-Meier analysis, and kappa assessment for intra- and inter-observer variability. ANP and CD34 were significantly overexpressed in IDCM compared to NH (p<0.05). Conversely, troponin T and nestin expression levels did not show significant variation. Inter-observer kappa statistics showed a value of 0.87 and intra-observer kappa statistics a value of 0.98. Evaluation of the marker distribution in the myocardium of patients with IDCM CD34 expression curve was similar to that of troponin T (p<0.0001), although two groups could be identified. Patients with a difference of more than 20 myocardial fibers in expression of CD34 and troponin T had a somewhat less favorable survival although the difference was not significant. The analysis of cells positive for troponin T resulted in a similar number of cardiac fibers between NH and IDCM. This is in agreement with cardiac enlargement present in IDCM, which is due to ventricular dilatation rather than increased number of myocytes. Moreover, the expression of nestin, a marker of activation of myocardial precursors, did not change either, and this may confirm that there are no hyperplastic phenomena in the IDCM pathogenesis. The increase in ANP-positive cells in IDCM could be a consequence of neurohormonal activation due to a decline in the impaired myocyte contractility. Furthermore, since it was already shown that ANP could be important in the control of vascular remodeling, we postulated that the increase in CD34-positive cells might be functionally correlated with the increase in ANP production. Differential expression of CD34 and troponin T might be used in future studies to evaluate their prognostic value.

In Utero Caffeine Exposure Induces Transgenerational Effects on the Adult Heart

“…These genes are associated with dilated cardiomyopathy 63 64 65 and we have demonstrated previously that their expression is sensitive to caffeine exposure 54 . In addition, we observe increased ANP expression in adult F1 hearts which is also increased in human idiopathic dilated cardiomyopathy 66 . From our RNAseq data we identify new genes that we had not previously associated with caffeine exposure and cardiomyopathy, including Nppb which is up regulated in F1 hearts at one year and in dilated cardiomyopathy 67 , and Mylk4 which is down regulated in our caffeine exposed F1 hearts and in human dilated cardiomyopathy patient left ventricle tissue 68 .…”

Predicting the Risk to Develop Preeclampsia in the First Trimester Combining Promoter Variant -98A/C of LGALS13 (Placental Protein 13), Black Ethnicity, Previous Preeclampsia, Obesity, and Maternal Age

“…At the same time, the latter two variants of polymorphisms have been shown to be closely related to other cardiovascular disorders, including congestive cardiomyopathy, supraventricular arrhythmias, reduced exercise capacity, and an increase in left ventricular systolic dimension. These disorders underline high susceptibility for cardiovascular morbidity among women who had experienced hypertensive disorders in pregnancy [41–42]. …”

Dilated cardiomyopathy etio-morphologic investigation

“…In a recent study, atrial natriuretic protein (ANP) and CD34 (an endothelial and stem cell marker) were significantly over-expressed in IDCM compared to normal heart (NH). Patients with a difference of more than 20 myocardial fibers in the compared expression between CD34 and troponin T were associated with a quite less favorable survival although the difference was not significant (13). The increase in ANP positive cells in IDCM could be a consequence of neuro-hormonal activation due to a decline of the impaired myocyte contractility.…”