Circulating angiogenic precursors in idiopathic pulmonary arterial hypertension

Kewal Asosingh, Micheala A. Aldred, Amit Vasanji, Judith Drazba, Jacqueline Sharp, Carol Farver, Suzy A.A. Comhair, Weiling Xu, Lauren Licina, Lan Huang, Bela Anand-Apte, Mervin C. Yoder, Rubin M. Tuder, Serpil C. Erzurum

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

Vascular remodeling in idiopathic pulmonary arterial hypertension (IPAH) involves hyperproliferative and apoptosis-resistant pulmonary artery endothelial cells. In this study, we evaluated the relative contribution of bone marrow-derived proangiogenic precursors and tissue-resident endothelial progenitors to vascular remodeling in IPAH. Levels of circulating CD34 +CD133+ bone marrow-derived proangiogenic precursors were higher in peripheral blood from IPAH patients than in healthy controls and correlated with pulmonary artery pressure, whereas levels of resident endothelial progenitors in IPAH pulmonary arteries were comparable to those of healthy controls. Colony-forming units of endothelial-like cells (CFU-ECs) derived from CD34+CD133+ bone marrow precursors of IPAH patients secreted high levels of matrix metalloproteinase-2, had greater affinity for angiogenic tubes, and spontaneously formed disorganized cell clusters that increased in size in the presence of transforming growth factor-β or bone morphogenetic protein-2. Subcutaneous injection of NOD SCID mice with IPAH CFU-ECs within Matrigel plugs, but not with control CFU-ECs, produced cell clusters in the Matrigel and proliferative lesions in surrounding murine tissues. Thus, mobilization of high levels of proliferative bone marrow-derived proangiogenic precursors is a characteristic of IPAH and may participate in the pulmonary vascular remodeling process.

Original languageEnglish (US)
Pages (from-to)615-627
Number of pages13
JournalAmerican Journal of Pathology
Volume172
Issue number3
DOIs
StatePublished - Mar 2008

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Asosingh, K., Aldred, M. A., Vasanji, A., Drazba, J., Sharp, J., Farver, C., Comhair, S. A. A., Xu, W., Licina, L., Huang, L., Anand-Apte, B., Yoder, M. C., Tuder, R. M., & Erzurum, S. C. (2008). Circulating angiogenic precursors in idiopathic pulmonary arterial hypertension. American Journal of Pathology, 172(3), 615-627. https://doi.org/10.2353/ajpath.2008.070705