ArticleArteriosclerosis, thrombosis, and vascular biology2023
Flk1 Deficiency and Hypoxia Synergistically Promote Endothelial Dysfunction, Vascular Remodeling, and Pulmonary Hypertension.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Ambient PMEnvironment & health (Washington, D.C.) · 2026Article
- Advances in the pathogenesis and clinical management of pulmonary hypertension.Medical review (2021) · 2026Review
- The emerging role of integrin signaling in pulmonary vascular disease.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Deciphering the Counterintuitive Role of Vascular Endothelial Growth Factor Signaling Pathways in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2026Review
- Risk Factors, Pathogen Distribution, and Treatment Strategies for Mortality in Elderly Patients with Pulmonary Bacterial Infections.Clinical interventions in aging · 2026Article
- Nanoparticle delivery of VEGF and SDF-1α as an approach for treatment of pulmonary arterial hypertension.Pulmonary circulation · 2024Article
- Systematical Evaluation of the Structure-Cardiotoxicity Relationship of 7-Azaindazole-based PI3K Inhibitors Designed by Bioisosteric Approach.Cardiovascular toxicology · 2023Article
- Angiogenesis Redux: An Overall Protective Role of VEGF/KDR Signaling in the Microvasculature in Pulmonary Arterial Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe mechanisms underlying pulmonary hypertension (PH) remain largely unknown; further, why advanced vascular remodeling preferentially occurs in arterioles is yet to be answered. VEGF (vascular endothelial growth factor) regulates angiogenesis through Flk1 (fetal liver kinase 1) and Flt1 (fms-like tyrosine kinase 1) on endothelial cells (ECs), which may be related to PH pathogenesis. However, spatiotemporal expression patterns of Flk1 and Flt1 in the pulmonary vascular system and the role of endothelial Flk1 in PH development remain poorly understood.
methodsWe analyzed multiple reporter mice, including Flk1-GFP (green fluorescent protein) bacterial artificial chromosome transgenic (Tg), Flt1-DsRed bacterial artificial chromosome Tg, and Flk1-GFP/Flt1-DsRed double Tg mice, to determine the spatiotemporal expression of Flk1 and Flt1 in hypoxia-induced PH. We also used Cdh5
resultsFlk1 was specifically expressed in the ECs of small pulmonary vessels, including arterioles. Conversely, Flt1 was more broadly expressed in the ECs of large- to small-sized vessels in adult mouse lungs. Intriguingly, Flk1
conclusionsFlk1 and Flt1 were differentially expressed in pulmonary ECs. Flk1 deficiency and hypoxia jointly dysregulated arteriolar ECs to promote vascular remodeling. Thus, dysfunction of Flk1
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