ArticleMolecular and cellular biology2008
Rap1a is a key regulator of fibroblast growth factor 2-induced angiogenesis and together with Rap1b controls human endothelial cell functions.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
68 citing papers in PubMed, 121 citations in OpenAlex.
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- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Revealing genes related teat number traits via genetic variation in Yorkshire pigs based on whole-genome sequencing.BMC genomics · 2024Article
- Towards Targeting Endothelial Rap1B to Overcome Vascular Immunosuppression in Cancer.International journal of molecular sciences · 2024Review
- Buyang Huanwu decoction ameliorates myocardial injury and attenuates platelet activation by regulating the PI3 kinase/Rap1/integrin α(IIb)β(3) pathway.Chinese medicine · 2024Article
- Mitochondrial reactive oxygen species impact human fibroblast responses to protracted γ-ray exposures.International journal of radiation biology · 2024Article
- The circular RNANeural regeneration research · 2023Article
- Endothelial Rap1B mediates T-cell exclusion to promote tumor growth: a novel mechanism underlying vascular immunosuppression.Angiogenesis · 2023Article
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- Rap1a Activity Elevated the Impact of Endogenous AGEs in Diabetic Collagen to Stimulate Increased Myofibroblast Transition and Oxidative Stress.International journal of molecular sciences · 2022Article
- EPAC2 acts as a negative regulator in Matrigel-driven tubulogenesis of human microvascular endothelial cells.Scientific reports · 2021Article
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- Distinct Signaling Functions of Rap1 Isoforms in NO Release From Endothelium.Frontiers in cell and developmental biology · 2021Article
- Pravastatin-induced changes in expression of long non-coding and coding RNAs in endothelial cells.Physiological reports · 2021Article
- Medicinal Plant Leaf Extract From Sage and Lemon Verbena Promotes Intestinal Immunity and Barrier Function in Gilthead Seabream (Frontiers in immunology · 2021Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Angiogenesis, the formation of new blood vessels from existing vasculature, is regulated primarily by endothelial cell activity. We show herein that the Ras family GTPase Rap1 has a key role in the regulation of angiogenesis by modulating endothelial cell functions. Blood vessel growth into fibroblast growth factor 2 (FGF2)-containing Matrigel plugs was absent from rap1a(-/-) mice, and aortic rings derived from rap1a(-/-) mice failed to sprout primitive tubes in response to FGF2, when the tissue was embedded in Matrigel. Knocking down either rap1a or rap1b, two closely related rap1 family members, in human microvascular endothelial cells (HMVECs) by utilizing siRNA confirmed that Rap1 plays key roles in endothelial cell function. The rap1a or rap1b knockdown resulted in decreased adhesion to extracellular matrices and impaired cell migration. HMVEC monolayers lacking Rap1 had increased permeability, and Rap1-deficient endothelial cells failed to form three-dimensional tubular structures when they were plated on Matrigel in vitro. Finally, the activation levels of extracellular signal-regulated kinase (ERK), p38, and Rac, which are important signaling molecules in angiogenesis, were all reduced in response to FGF2 when either of the Rap1 proteins was depleted. These observations place Rap1 centrally in the human angiogenic process and suggest that both the Rap1a and Rap1b proteins are required for angiogenesis and that Rap1 is a critical mediator of FGF-induced ERK activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.