Abstract 15950: Increased Expression of the Neuronal/Mesenchymal Stem Cell Marker Nestin in Plexiform Lesions of Patients With Severe PAH
Progenitor cells has been shown in remodeled pulmonary arteries of patients with severe pulmonary arterial hypertension (PAH) and of animals with PAH induced by chronic hypoxia. But the primitive cells in the plexiform lesions of PAH patients are incompletely characterized. Nestin, a class VI family intermediate filament, has been originally identified in neuroepithelial stem cells of rats. Although Nestin expression has been later also found in mesenchymal stem cells, pericytes and neo-angiogenic endothelial cells, Nestin+ cells have not been identified in the vascular lesions on PAH patients.
We hypothesized that Nestin expression would be increased in the plexiform lesions of PAH patients.
We performed immunofluorescence stainings on lung tissue from patients with idiopathic PAH (iPAH), collagen vascular disease-associated pulmonary hypertension (PH-CVD) and from control subjects without evident pulmonary vascular disease.
We detected in images acquired by confocal microscopy in a randomized and blinded manner, increased numbers of Nestin+ cells in the remodeled pulmonary arteries of iPAH and PH-CVD. Nestin+ cells were frequently found in the vascular channels of plexiform lesions. Nestin+ cells were frequently positive for the endothelial cell marker von Willebrand factor (vWF), in particular in colander-like plexiform lesions. Some Nestin+ cells also expressed α-smooth muscle actin (α-SMA). Nestin+ vWF+ cells were more frequent in remodeled pulmonary arteries of PH-CVD patients. We then investigated whether Nestin+ cells may serve as a source of growth factors that regulate cell growth, stem cell differentiation and angiogenesis, such as Wnt1, bone morphogenic protein 4 (BMP4) and CXC chemokine ligand 12 (CXCL12). Nestin+ cells frequently expressed Wnt1, BMP4 and CXCL12. Whereas Nestin+ Wnt1+ and Nestin+ BMP4+ cells were more common in the remodeled vessels of PH-CVD patients, the number of Nestin+ CXCL12+ cells were equally elevated in the plexiform lesions of the iPAH and PH-CVD groups.In conclusion, cells expressing the intermediate filament Nestin can be found in pulmonary vascular lesions of patients with iPAH and PH-CVD. Our results indicate potential differences between the vascular lesions from different PAH entities.
- © 2013 by American Heart Association, Inc.