ArticleProceedings of the National Academy of Sciences of the United States of America2021
MEKK3-TGFβ crosstalk regulates inward arterial remodeling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Inhibition of MEKK3 Prevents Cerebral Cavernous Malformation Progression Via Restoring Endothelial Integrity and Restricting Microglial Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From Byproduct to Regulator: The Expanding Role of Lactate and Lactylation in Cardiovascular Physiology and Disease.Biology · 2026Review
- FOXO1 Integrates Endothelial Hemodynamic, Inflammatory, and Metabolic Pathways in Atherosclerosis.Circulation research · 2026Article
- Endothelial to mesenchymal transition in cardiovascular diseases: molecular insights and clinical perspectives.European heart journal · 2026Review
- TGF-β: The Molecular Mechanisms of Atherosclerosis - insights into SMAD Pathways and Gene Therapy Prospects.Current medicinal chemistry · 2026Review
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Hemodynamic forces prevent myxomatous valve disease in mice through KLF2/4 signaling.The Journal of clinical investigation · 2025Article
- Fluid Shear Stress-Regulated Vascular Remodeling: Past, Present, and Future.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- cSTAR analysis identifies endothelial cell cycle as a key regulator of flow-dependent artery remodeling.Science advances · 2025Article
- Advances in Shear Stress Stimulation of Stem Cells: A Review of the Last Three Decades.Biomedicines · 2024Review
- A KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling.Nature cardiovascular research · 2024Article
- BMPER regulates arterial adaptation to flow.Nature cardiovascular research · 2024Article
- New progress in roles of TGF-β signaling crosstalks in cellular functions, immunity and diseases.Cell regeneration (London, England) · 2024Article
- NKX2-5 regulates vessel remodeling in scleroderma-associated pulmonary arterial hypertension.JCI insight · 2024Article
- Endothelial to mesenchymal transition: at the axis of cardiovascular health and disease.Cardiovascular research · 2024Review
- TRAF7 is an essential regulator of blood vessel integrity during mouse embryonic and neonatal development.iScience · 2023Article
- Endothelial-to-mesenchymal transition: advances and controversies.Current opinion in physiology · 2023Article
- Relationship of Sulfatides Physiological Function and Peroxisome Proliferator-Activated Receptor α.Neurochemical research · 2023Review
- High-resolution visualization of pial surface vessels by flattened whole mount staining.iScience · 2023Article
- Single Nucleotide Polymorphism rs9277336 Controls the Nuclear Alpha Actinin 4-Human Leukocyte Antigen-DPA1 Axis and Pulmonary Endothelial Pathophenotypes in Pulmonary Arterial Hypertension.Journal of the American Heart Association · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Arterial remodeling is an important adaptive mechanism that maintains normal fluid shear stress in a variety of physiologic and pathologic conditions. Inward remodeling, a process that leads to reduction in arterial diameter, plays a critical role in progression of such common diseases as hypertension and atherosclerosis. Yet, despite its pathogenic importance, molecular mechanisms controlling inward remodeling remain undefined. Mitogen-activated protein kinases (MAPKs) perform a number of functions ranging from control of proliferation to migration and cell-fate transitions. While the MAPK ERK1/2 signaling pathway has been extensively examined in the endothelium, less is known about the role of the MEKK3/ERK5 pathway in vascular remodeling. To better define the role played by this signaling cascade, we studied the effect of endothelial-specific deletion of its key upstream MAP3K, MEKK3, in adult mice. The gene's deletion resulted in a gradual inward remodeling of both pulmonary and systematic arteries, leading to spontaneous hypertension in both vascular circuits and accelerated progression of atherosclerosis in hyperlipidemic mice. Molecular analysis revealed activation of TGFβ-signaling both in vitro and in vivo. Endothelial-specific TGFβR1 knockout prevented inward arterial remodeling in MEKK3 endothelial knockout mice. These data point to the unexpected participation of endothelial MEKK3 in regulation of TGFβR1-Smad2/3 signaling and inward arterial remodeling in artery diseases.
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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.