Nestin represents a potential marker of pulmonary vascular remodeling in pulmonary arterial hypertension associated with congenital heart disease.
OBJECTIVE
Reportedly, nestin was re-expressed in proliferative synthetic-type pulmonary artery smooth muscle cells (PASMCs) and obligatory for PASMC proliferation in pulmonary arterial hypertension (PAH). Accordingly, nestin is increased in pulmonary vascular lesions of congenital heart disease (CHD)-associated PAH patients. We tested the hypothesis whether nestin was re-expressed in proliferative synthetic-type PASMCs and associated with pulmonary vascular remodeling in CHD-PAH.


MATERIALS AND METHODS
Nestin expression was tested using lung tissues from CHD-PAH patients and monocrotaline (MCT) plus aortocaval (AV) shunt-induced PAH rats, human PASMCs (HPASMCs), and pulmonary artery endothelial cells (PAECs) and PASMCs from MCT-AV-induced PAH rats. The role and possible mechanism of nestin on HPASMC proliferation, apoptosis, cell cycle and migration were investigated by assays of CCK-8, EdU, TUNEL, flow cytometry, transwell chamber and immunoblotting assays.


RESULTS
Nestin was solely expressed in proliferative synthetic-type PASMCs, but rarely detected in PAECs. Nestin was barely detected in normal pulmonary arterioles and occlusive pulmonary vascular lesions. Its expression was robustly increased in developing pulmonary vasculature, but returned to normal levels at the late stage of pulmonary vascular remodeling in lung tissues from CHD-PAH patients and MCT-AV-induced PAH rats. Besides, nestin peaks were consistent with the histological features in lung tissues of MCT-AV-induced PAH rats. Moreover, nestin overexpression effectively promoted HPASMC phenotypic transformation, proliferation, apoptosis resistance and migration via enhancing Wnt/β-catenin activation.


CONCLUSIONS
These data indicated that nestin was re-expressed in proliferative synthetic-type PASMCs and might represent a potential marker of pulmonary vascular remodeling in CHD-PAH.
['Zhou|Jing-Jing|JJ|', 'Li|Huang|H|', 'Qian|Yu-Ling|YL|', 'Quan|Rui-Lin|RL|', 'Chen|Xiao-Xi|XX|', 'Li|Li|L|', 'Li|Yue|Y|', 'Wang|Pei-He|PH|', 'Meng|Xian-Min|XM|', 'Jing|Xiao-Li|XL|', 'He|Jian-Guo|JG|']
D000293:Adolescent D000328:Adult D000368:Aged D000818:Animals D015415:Biomarkers D002648:Child D002675:Child, Preschool D042783:Endothelial Cells D005260:Female D006330:Heart Defects, Congenital D006801:Humans D008168:Lung D008297:Male D008875:Middle Aged D016686:Monocrotaline D032389:Myocytes, Smooth Muscle D064231:Nestin D010641:Phenotype D018809:Proliferating Cell Nuclear Antigen D000081029:Pulmonary Arterial Hypertension D011651:Pulmonary Artery D017207:Rats, Sprague-Dawley D013997:Time Factors D066253:Vascular Remodeling D060449:Wnt Signaling Pathway D055815:Young Adult
Nestin Pulmonary arterial hypertension Congenital heart disease Pulmonary arterial smooth muscle cell Wnt/β-catenin