PT  - JOURNAL ARTICLE
AU  - Farhan Saboor
AU  - Ansgar N. Reckmann
AU  - Claudia U.M. Tomczyk
AU  - Dorothea M. Peters
AU  - Norbert Weissmann
AU  - Andre Kaschtanow
AU  - Ralph T. Schermuly
AU  - Tatyana V. Michurina
AU  - Grigori Enikolopov
AU  - Dieter Müller
AU  - Andrea Mietens
AU  - Ralf Middendorff
TI  - Nestin-expressing vascular wall cells drive development of pulmonary hypertension
AID  - 10.1183/13993003.00574-2015
DP  - 2016 Mar 01
TA  - European Respiratory Journal
PG  - 876--888
VI  - 47
IP  - 3
4099  - http://erj.ersjournals.com/content/47/3/876.short
4100  - http://erj.ersjournals.com/content/47/3/876.full
SO  - Eur Respir J2016 Mar 01; 47
AB  - Nestin, a well-known marker of neuronal stem cells, was recently suggested to characterise stem cell-like progenitors in non-neuronal structures during development and tissue repair. Integrating novel morphological approaches (CLARITY), we investigate whether nestin expression defines the proliferating cell population that essentially drives vascular remodelling during development of pulmonary hypertension.The role of nestin was investigated in lungs of nestin-GFP (green fluorescent protein) mice, models of pulmonary hypertension (rat: monocrotaline, SU5416/hypoxia; mouse: hypoxia), samples from pulmonary hypertension patients and human pulmonary vascular smooth muscle cells (VSMCs).Nestin was solely found in lung vasculature and localised to proliferating VSMCs, but not bronchial smooth muscle cells. Nestin was shown to affect cell number and was significantly enhanced in lungs early during development of pulmonary hypertension, correlating well with increased VSMC proliferation, expression of phosphorylated (activated) platelet-derived growth factor receptor β and downregulation of the smooth muscle cell differentiation marker calponin. At later time points when pulmonary hypertension became clinically evident, nestin expression and proliferation returned to control levels. Increase of nestin-positive VSMCs was also found in human pulmonary hypertension, both in vessel media and neointima.Nestin expression seems to be obligatory for VSMC proliferation, and specifies lung vascular wall cells that drive remodelling and (re-)generation. Our data promise novel diagnostic tools and therapeutic targets for pulmonary hypertension.In lung, nestin is solely found in vascular smooth muscle cells and drives remodelling in pulmonary hypertension http://ow.ly/StPCS