Biomedical subjects
Publications and source records attributed to Steven D Zangwill.
We report a case of histiocytoid cardiomyopathy in a 30-month-old child. This rare disorder has been identified in <100 patients worldwide and no previous reports of cardiac transplantation with this condition have been identified. We reviewed the clinical and pathologic findings and compared them to previous studies.
Commotio cordis is ventricular fibrillation that results from blunt chest trauma and is a life threatening condition; early resuscitation and defibrillation are critical. This may occur during sporting events or from child abuse and most patients are boys who are younger than 16 years. Commotio cordis' prognosis depends on the availability of cardiac defibrillation. Automatic defibrillators at convenient locations near sporting events, combined with improved cardiopulmonary resuscitation education, may improve chances of survival after this rare phenomenon. Transient cardiac conduction abnormalities and arrhythmias have been observed in survivors; therefore, cardiac clearance before resumption of sports is indicated.
Nuclear factor of activated T cells, Cytoplasmic 1 (NFATc1) is required for heart valve formation. Vascular endothelial growth factor (VEGF) signaling, mediated by NFATc1 activation, positively regulates growth of valvular endothelial cells. However, regulators of VEGF/NFATc1 signaling in valve endothelium are poorly understood. Peroxisome proliferator-activated receptor gamma (PPARgamma) inhibits NFATc1 activity in T cells and cardiomyocytes, but it is not known if PPARgamma controls NFATc1 function in endothelial cells. The authors hypothesize PPARgamma antagonizes VEGF signaling in valve endothelium by inhibiting NFATc1. Endothelial cells isolated from human valve leaflet tissue were shown by immunocytochemistry to express the endothelial-specific markers von Willebrand factor (vWF) and platelet endothelial cell adhesion molecule (PECAM)-1. VEGF-induced proliferation and migration of human pulmonary valve endothelial cells (HPVECs) were inhibited by rosiglitazone (ROSI), a specific ligand of PPARgamma activation, suggesting that PPARgamma disrupts VEGF signaling in the valve endothelium. ROSI also antagonized VEGF-mediated NFATc1 nuclear translocation in HPVECs, suggesting that PPARgamma inhibits VEGF signaling of NFATc1 activation in the valve. The effect of ROSI on nonvalve human umbilical vein endothelial cells (HUVECs) was tested in parallel and a similar inhibition of NFATc1 activation was observed. These data provide the first demonstration that ROSI negatively regulates VEGF signaling in the valve endothelium by a mechanism involving NFATc1 activation and nuclear translocation.