{"entity": "researcher", "timestamp": "2026-03-09T08:41:44.576Z", "family": "Petkova", "given": "Milena", "initials": "M", "orcid": "0000-0002-7186-7256", "affiliations": ["Department of Immunology, Genetics and Pathology, Uppsala University , Uppsala, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/458b9dbc408c4118b97be343da8b3b49.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/458b9dbc408c4118b97be343da8b3b49"}}, "publications": [{"entity": "publication", "iuid": "8da9f8bb7e024de5b9d404a6ed360d99", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8da9f8bb7e024de5b9d404a6ed360d99.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8da9f8bb7e024de5b9d404a6ed360d99"}}, "title": "Angiopoietin-TIE2 feedforward circuit promotes PIK3CA-driven venous malformations.", "authors": [{"family": "Kraft", "given": "Marle", "initials": "M", "orcid": "0000-0002-3523-7003", "researcher": {"href": "https://publications.scilifelab.se/researcher/6bac6d144f4143b7ad9ad0a9058d95a0.json"}}, {"family": "Schoofs", "given": "Hans", "initials": "H", "orcid": "0000-0003-3429-912X", "researcher": {"href": "https://publications.scilifelab.se/researcher/32c662013aae42298c0776802f3628fa.json"}}, {"family": "Petkova", "given": "Milena", "initials": "M", "orcid": "0000-0002-7186-7256", "researcher": {"href": "https://publications.scilifelab.se/researcher/458b9dbc408c4118b97be343da8b3b49.json"}}, {"family": "Andrade", "given": "Jorge", "initials": "J", "orcid": "0000-0002-4577-8620", "researcher": {"href": "https://publications.scilifelab.se/researcher/477b341b9d0048dab408f6106fc5b915.json"}}, {"family": "Grosso", "given": "Ana Rita", "initials": "AR", "orcid": "0000-0001-6974-4209", "researcher": {"href": "https://publications.scilifelab.se/researcher/07a33297431f417eaabbdbe477c06c4f.json"}}, {"family": "Benedito", "given": "Rui", "initials": "R", "orcid": "0000-0003-2458-3055", "researcher": {"href": "https://publications.scilifelab.se/researcher/e15242bf49384c309118be8db7abe19a.json"}}, {"family": "De Roo", "given": "An-Katrien", "initials": "AK", "orcid": "0000-0002-0000-1260", "researcher": {"href": "https://publications.scilifelab.se/researcher/108ee3be589741e28c1e676b248ec20f.json"}}, {"family": "Boon", "given": "Laurence M", "initials": "LM", "orcid": "0000-0001-8273-3328", "researcher": {"href": "https://publications.scilifelab.se/researcher/5bdedae62ce74bd08d22df3bd007e76a.json"}}, {"family": "Vikkula", "given": "Miikka", "initials": "M", "orcid": "0000-0002-6236-338X", "researcher": {"href": "https://publications.scilifelab.se/researcher/14ec2db8cf364aa383bcac2ebf64cc39.json"}}, {"family": "Kapp", "given": "Friedrich G", "initials": "FG", "orcid": "0000-0002-2729-6177", "researcher": {"href": "https://publications.scilifelab.se/researcher/392ca5f5f1914e0585da18619bda2c00.json"}}, {"family": "H\u00e4gerling", "given": "Ren\u00e9", "initials": "R", "orcid": "0000-0002-6830-2043", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc9254578d4a4ee8b7d24b2e4a3025ab.json"}}, {"family": "Potente", "given": "Michael", "initials": "M", "orcid": "0000-0002-5689-0036", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2fbc439106a4708b03a324aa5499f47.json"}}, {"family": "M\u00e4kinen", "given": "Taija", "initials": "T", "orcid": "0000-0002-9338-1257", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf99a0589d1f4532b532bfc575edaada.json"}}], "type": "journal article", "published": "2025-07-00", "journal": {"title": "Nat Cardiovasc Res", "issn": "2731-0590", "volume": "4", "issue": "7", "pages": "801-820", "issn-l": null}, "abstract": "Venous malformations (VMs) are vascular anomalies lacking curative treatments, often caused by somatic PIK3CA mutations that hyperactivate the PI3K\u03b1-AKT-mTOR signaling pathway. Here, we identify a venous-specific signaling circuit driving disease progression, where excessive PI3K\u03b1 activity amplifies upstream TIE2 receptor signaling through autocrine and paracrine mechanisms. In Pik3caH1047R-driven VM mouse models, single-cell transcriptomics and lineage tracking revealed clonal expansion of mutant endothelial cells with a post-capillary venous phenotype, characterized by suppression of the AKT-inhibited FOXO1 and its target genes, including the TIE2 antagonist ANGPT2. An imbalance in TIE2 ligands, likely exacerbated by aberrant recruitment of smooth muscle cells producing the agonist ANGPT1, increased TIE2 activity in both mouse and human VMs. While mTOR blockade had limited effects on advanced VMs in mice, inhibiting TIE2 or ANGPT effectively suppressed their growth. These findings uncover a PI3K-FOXO1-ANGPT-TIE2 circuit as a core driver of PIK3CA-related VMs and highlight TIE2 as a promising therapeutic target.", "doi": "10.1038/s44161-025-00655-9", "pmid": "40410415", "labels": {"Bioinformatics (NBIS)": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12259471"}, {"db": "pii", "key": "10.1038/s44161-025-00655-9"}], "notes": [], "created": "2025-11-18T11:56:53.465Z", "modified": "2025-11-28T10:48:02.845Z"}, {"entity": "publication", "iuid": "4371a4380e6d4e3294f5c4116411dd13", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4371a4380e6d4e3294f5c4116411dd13.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4371a4380e6d4e3294f5c4116411dd13"}}, "title": "Immune-interacting lymphatic endothelial subtype at capillary terminals drives lymphatic malformation.", "authors": [{"family": "Petkova", "given": "Milena", "initials": "M", "orcid": "0000-0002-7186-7256", "researcher": {"href": "https://publications.scilifelab.se/researcher/458b9dbc408c4118b97be343da8b3b49.json"}}, {"family": "Kraft", "given": "Marle", "initials": "M", "orcid": "0000-0002-3523-7003", "researcher": {"href": "https://publications.scilifelab.se/researcher/6bac6d144f4143b7ad9ad0a9058d95a0.json"}}, {"family": "Stritt", "given": "Simon", "initials": "S", "orcid": "0000-0002-4299-4934", "researcher": {"href": "https://publications.scilifelab.se/researcher/b561f8d6fb1a46d0ae76c66e440956a1.json"}}, {"family": "Martinez-Corral", "given": "Ines", "initials": "I", "orcid": "0000-0001-9194-2412", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f961131890c4422b8ce5a5d2d1f1dc9.json"}}, {"family": "Orts\u00e4ter", "given": "Henrik", "initials": "H", "orcid": "0000-0002-4046-4702", "researcher": {"href": "https://publications.scilifelab.se/researcher/1f597cc7c8104728ae168db36a8ee9e7.json"}}, {"family": "Vanlandewijck", "given": "Michael", "initials": "M", "orcid": "0000-0002-0709-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa2148fbafb44d59bd110e36bd77769c.json"}}, {"family": "Jakic", "given": "Bojana", "initials": "B", "orcid": "0000-0002-2339-5928", "researcher": {"href": "https://publications.scilifelab.se/researcher/31f0bb6137144060a45a40650aacadc7.json"}}, {"family": "Baselga", "given": "Eul\u00e0lia", "initials": "E", "orcid": "0000-0003-1086-8439", "researcher": {"href": "https://publications.scilifelab.se/researcher/12b835a79f01492e82d1280c8050e01b.json"}}, {"family": "Castillo", "given": "Sandra D", "initials": "SD", "orcid": "0000-0002-7007-3155", "researcher": {"href": "https://publications.scilifelab.se/researcher/de3d0367a9d8474197f66365c1b5c040.json"}}, {"family": "Graupera", "given": "Mariona", "initials": "M", "orcid": "0000-0003-4608-4185", "researcher": {"href": "https://publications.scilifelab.se/researcher/76ead57229884f90bff307099a9a70ea.json"}}, {"family": "Betsholtz", "given": "Christer", "initials": "C", "orcid": "0000-0002-8494-971X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a00cfe9d521047f280978d84d7dcf1b3.json"}}, {"family": "M\u00e4kinen", "given": "Taija", "initials": "T", "orcid": "0000-0002-9338-1257", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf99a0589d1f4532b532bfc575edaada.json"}}], "type": "journal article", "published": "2023-04-03", "journal": {"title": "J. Exp. Med.", "issn": "1540-9538", "volume": "220", "issue": "4", "issn-l": "0022-1007"}, "abstract": "Oncogenic mutations in PIK3CA, encoding p110\u03b1-PI3K, are a common cause of venous and lymphatic malformations. Vessel type-specific disease pathogenesis is poorly understood, hampering development of efficient therapies. Here, we reveal a new immune-interacting subtype of Ptx3-positive dermal lymphatic capillary endothelial cells (iLECs) that recruit pro-lymphangiogenic macrophages to promote progressive lymphatic overgrowth. Mouse model of Pik3caH1047R-driven vascular malformations showed that proliferation was induced in both venous and lymphatic ECs but sustained selectively in LECs of advanced lesions. Single-cell transcriptomics identified the iLEC population, residing at lymphatic capillary terminals of normal vasculature, that was expanded in Pik3caH1047R mice. Expression of pro-inflammatory genes, including monocyte/macrophage chemokine Ccl2, in Pik3caH1047R-iLECs was associated with recruitment of VEGF-C-producing macrophages. Macrophage depletion, CCL2 blockade, or anti-inflammatory COX-2 inhibition limited Pik3caH1047R-driven lymphangiogenesis. Thus, targeting the paracrine crosstalk involving iLECs and macrophages provides a new therapeutic opportunity for lymphatic malformations. Identification of iLECs further indicates that peripheral lymphatic vessels not only respond to but also actively orchestrate inflammatory processes.", "doi": "10.1084/jem.20220741", "pmid": "36688917", "labels": {"Bioinformatics Support and Infrastructure": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9884640"}, {"db": "pii", "key": "213817"}], "notes": [], "created": "2023-11-16T12:40:26.995Z", "modified": "2024-01-16T13:48:33.714Z"}]}