BMP9 induces cord blood-derived endothelial progenitor cell differentiation and ischemic neovascularization via ALK1

Jihye Kim, Minhyung Kim, Yoonjeong Jeong, Wook Bin Lee, Hyojin Park, Ja Young Kwon, Young Myeong Kim, Daehee Hwang, Young-Guen Kwon

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective - Modulating endothelial progenitor cells (EPCs) is essential for therapeutic angiogenesis, and thus various clinical trials involving EPCs are ongoing. However, the identification of environmental conditions and development of optimal methods are required to accelerate EPC-driven vasculogenesis. Approach and Results - We evaluated gene expression profiles of cord blood-derived EPCs and endothelial cells to identify the key factors in EPC→endothelial cell differentiation and to show that transforming growth factor-β family members contribute to EPC differentiation. The expression levels of activin receptor-like kinase 1 (ALK1) and its high-affinity ligand, bone morphogenetic protein 9 (BMP9) were markedly changed in EPC→endothelial cell differentiation. Interestingly, BMP9 induced EPC→endothelial cell differentiation and EPC incorporation into vessel-like structures by acting on ALK1 expressed on EPCs in vitro. BMP9 also induced neovascularization in mice with hindlimb ischemia by increasing vessel formation and the incorporation of EPCs into vessels. Conversely, neovascularization was impaired when ALK1 signaling was blocked. Furthermore, EPCs exposed to either short- or long-term BMP9 stimulation demonstrated these functions in EPC-mediated neovascularization. Conclusions - Collectively, our results indicated that BMP9/ALK1 augmented vasculogenesis and angiogenesis, and thereby enhanced neovascularization. Thus, we suggest that BMP9/ALK1 may improve the efficacy of EPC-based therapies for treating ischemic diseases.

Original languageEnglish
Pages (from-to)2020-2031
Number of pages12
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume35
Issue number9
DOIs
Publication statusPublished - 2015 Jan 1

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this