title: Monocyte-secreted Wnt5a interacts with FZD5 in microvascular endothelial cells and induces angiogenesis through tissue factor signaling.
abstract: Angiogenesis during reactive and pathologic processes is characteristically associated with inflammation. Inflammatory cells participate in angiogenesis by secreting different molecules that affect endothelial cell functions. We had previously shown that induced tissue factor (TF) expression in activated microvascular endothelial cells (mEC) is able to induce angiogenesis via autocrine regulation. However, the signals that induce TF expression in mEC are not fully known. Here, we demonstrate that monocyte paracrine cross-talk with mECs triggers mEC-TF expression. We have identified that monocyte-secreted Wnt5a induces TF expression in mEC and functionally induces cell monolayer repair and angiotube formation in vitro as well as microvessel formation in vivo. Monocyte-secreted Wnt5a activates FZD5 in mECs, which signals to induce the release of intracellular Ca(2+) and increase NFκB transcription activity and TF gene expression. In sum, Wnt5a secreted by monocytes signals through the noncanonical Wnt-FZD5 pathway in mECs to induce TF expression that induces angiogenesis by autocrine regulation.
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC), Institut d'Investigació Biomèdica Sant Pau (IIB-Sant Pau) and Universitat Autònoma de Barcelona (UAB), Barcelona 08025, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Arderiu
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC), Institut d'Investigació Biomèdica Sant Pau (IIB-Sant Pau) and Universitat Autònoma de Barcelona (UAB), Barcelona 08025, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Espinosa
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC), Institut d'Investigació Biomèdica Sant Pau (IIB-Sant Pau) and Universitat Autònoma de Barcelona (UAB), Barcelona 08025, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Peña
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC), Institut d'Investigació Biomèdica Sant Pau (IIB-Sant Pau) and Universitat Autònoma de Barcelona (UAB), Barcelona 08025, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Aledo
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC), Institut d'Investigació Biomèdica Sant Pau (IIB-Sant Pau) and Universitat Autònoma de Barcelona (UAB), Barcelona 08025, Spain lbadimon@csic-iccc.org.
authors.forename: Lina
authors.initials: L
authors.lastname: Badimon
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D055806:Microvessels / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000071818:Wnt-5a Protein
chemical_list: C498589:FZD5 protein, human; D051157:Frizzled Receptors; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D013925:Thromboplastin
keywords: angiogenesis; microvascular endothelial cells; monocytes; tissue factor; wnt5a