0074 : Resident PW1+ progenitor cells participate in vascular remodeling during pulmonary arterial hypertension

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• 作者：France Dierick¹ ; Tiphaine Hé ; ry¹ ; Bé ; né ; dicte Hoareau¹ ; Nathalie Mougenot¹ ; Virginie Monceau¹ ; Caroline Claude¹ ; Mihaela Crisan² ; Vanessa Besson¹ ; Peter Dö ; rfmuller³ ; Gilles Marodon⁴ ; Elie Fadel⁵ ; Marc Humbert⁶ ; Elisa Yaniz-Galende¹ ; Jean-Sé ; bastien Hulot¹ ; Giovanna Marazzi¹ ; David Sassoon¹ ; Florent Soubrier¹ ; Sophie Nadaud¹ ; ^{sophie.nadaud@upmc.fr" class="auth_mail" title="E-mail the corresponding author}
• 刊名：Archives of Cardiovascular Diseases Supplements
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：8
• 期：3
• 页码：247
• 全文大小：51 K

文摘

Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling and neomuscularization. PW1+ progenitor cells can differentiate into smooth muscle cells (SMC) in vitro.

Objective

To determine the role of pulmonary PW1+ progenitor cells in vascular remodeling characteristic of PAH.

Methods and results

We investigated their contribution during chronic hypoxia (CH)-induced vascular remodeling in Pw1nLacZ+/– mouse expressing β-galactosidase in PW1+ cells and in differentiated cells derived from PW1+ cells. PW1+ progenitor cells are present in the perivascular zone in rodent and human control lungs. Using progenitor markers, three distinct myogenic PW1+ cell populations were isolated from the mouse lung of which two were significantly increased after 4 days of CH. The number of proliferating pulmonary PW1+ cells and the proportion of β-gal+ vascular SMC were increased, indicating a recruitment of PW1+ cells and their differentiation into vascular SMC during early CH-induced neomuscularization. CXCR4 inhibition using AMD3100 prevented PW1+ cells differentiation into SMC but did not inhibit their proliferation. Bone marrow transplantation experiments showed that the newly formed β-gal+ SMC were not derived from circulating bone marrow-derived PW1+ progenitor cells, confirming a resident origin of the recruited PW1+ cells. The number of pulmonary PW1+ cells was also increased in rats after monocrotaline (MCT) injection. In the human PAH lung, PW1-expressing cells were observed in large numbers in remodeled vascular structures.

Conclusions

These results demonstrate the existence of a novel population of resident SMC progenitor cells expressing PW1 and participating in PAHassociated vascular remodeling.

The author hereby declares no conflict of interest