Jihye Kim1, Minhyung Kim1, Yoonjeong Jeong1, Wook-Bin Lee1, Hyojin Park1, Ja-Young Kwon1, Young-Myeong Kim1, Daehee Hwang1, Young-Guen Kwon2. 1. From the Department of Biochemistry, College of Life Science and Biotechnology (J.K., Y.J., W.-b.L., H.P., Y.-G.K.) and Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, College of Medicine (J.-Y.K.), Yonsei University, Seoul, Korea; School of Interdisciplinary Biosciences and Bioengineering, Pohang University of Science and Technology, Pohang, Korea (M.K., D.H.); Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Korea (M.K.); and Department of new Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea (D.H.). 2. From the Department of Biochemistry, College of Life Science and Biotechnology (J.K., Y.J., W.-b.L., H.P., Y.-G.K.) and Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, College of Medicine (J.-Y.K.), Yonsei University, Seoul, Korea; School of Interdisciplinary Biosciences and Bioengineering, Pohang University of Science and Technology, Pohang, Korea (M.K., D.H.); Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Korea (M.K.); and Department of new Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea (D.H.). ygkwon@yonsei.ac.kr.
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.
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.
Authors: Heon-Woo Lee; Diana C Chong; Roxana Ola; William P Dunworth; Stryder Meadows; Jun Ka; Vesa M Kaartinen; Yibing Qyang; Ondine Cleaver; Victoria L Bautch; Anne Eichmann; Suk-Won Jin Journal: Arterioscler Thromb Vasc Biol Date: 2017-02-23 Impact factor: 8.311
Authors: Cavin K Ward-Caviness; Lucas M Neas; Colette Blach; Carol S Haynes; Karen LaRocque-Abramson; Elizabeth Grass; Elaine Dowdy; Robert B Devlin; David Diaz-Sanchez; Wayne E Cascio; Marie Lynn Miranda; Simon G Gregory; Svati H Shah; William E Kraus; Elizabeth R Hauser Journal: PLoS One Date: 2016-04-15 Impact factor: 3.240
Authors: Sami Mostafa; Mikhail Pakvasa; Elam Coalson; Allen Zhu; Alex Alverdy; Hector Castillo; Jiaming Fan; Alex Li; Yixiao Feng; Di Wu; Elliott Bishop; Scott Du; Mia Spezia; Alissa Li; Ofir Hagag; Alison Deng; Winny Liu; Mingyang Li; Sherwin S Ho; Aravind Athiviraham; Michael J Lee; Jennifer Moriatis Wolf; Guillermo A Ameer; Hue H Luu; Rex C Haydon; Jason Strelzow; Kelly Hynes; Tong-Chuan He; Russell R Reid Journal: Genes Dis Date: 2019-07-24