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Can J Physiol Pharmacol. 2018 Dec 17. doi: 10.1139/cjpp-2018-0424. [Epub ahead of print]

Myeloid angiogenic cells exhibit impaired migration, reduced expression of endothelial markers and increased apoptosis in idiopathic pulmonary arterial hypertension.

Author information

1
St Michael's Hospital, Toronto, Canada ; zhangq@smh.ca.
2
Guy's and St Thomas' Hospital NHS Trust, London, United Kingdom of Great Britain and Northern Ireland ; liana.zucco@gmail.com.
3
University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom of Great Britain and Northern Ireland ; marktoshner@hotmail.com.
4
University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom of Great Britain and Northern Ireland ; nwm23@cam.ac.uk.
5
Univeristy Health Network, Respirology, Toronto, Ontario, Canada ; john.granton@uhn.ca.
6
Ottawa Hospital Research Institute, Ottawa, Canada ; djstewart@ohri.ca.
7
St. Michael's Hospital, Cardiology , 30 Bond Street , Toronto, Ontario, Ontario, Canada , M5B 1W8 ; kutrykm@smh.ca.

Abstract

Idiopathic pulmonary arterial hypertension (IPAH) is a rare and devastating condition. There is no known cure for IPAH, and current treatment options are not always effective. Autologous myeloid angiogenic cells (MACs) have been explored as a novel therapy for IPAH but preliminary data from clinical trials show limited beneficial effects. A complete understanding of IPAH MAC function remains elusive. This study was designed to comprehensively compare cell function between IPAH MACs and healthy control MACs. MACs were procured through the culture of peripheral blood mononuclear cells in endothelial selective medium for 7 days. Compared with healthy MACs, IPAH MACs exhibited 1) significantly lower levels of endothelial markers as shown by fluorescence microscopy; 2) a markedly higher rate of apoptosis under both normal culture condition and serum starvation as shown by the TUNEL assay; 3) significantly decreased migration towards VEGF as shown by a modified Boyden chamber migration assay; and 4) similar VEGF and eNOS mRNA levels as shown by RT-qPCR. In conclusion, various aspects of IPAH MAC function are impaired. In order to achieve greater therapeutic benefits, pharmacologic and/or genetic manipulations to improve IPAH MAC function, particularly to promote cell survival and migration, are warranted.

PMID:
30557040
DOI:
10.1139/cjpp-2018-0424

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