ArticleNature cardiovascular research2024
A KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling.
Article in Nature cardiovascular research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Loss of Smad4 drives vascular malformations via c-KIT-dependent high-fluid shear stress mimicry.The Journal of clinical investigation · 2026Article
- Deletion of endothelial KLF4 as a model for preeclampsia.bioRxiv : the preprint server for biology · 2026Article
- FOXO1 Integrates Endothelial Hemodynamic, Inflammatory, and Metabolic Pathways in Atherosclerosis.Circulation research · 2026Article
- Linking cross-species trajectories of cerebrovascular remodeling in aging and Alzheimer's disease to brain vessel transcriptome.bioRxiv : the preprint server for biology · 2026Article
- Endothelial Klf9 fine-tunes Akt signaling to act as a transcriptional brake restraining retinal angiogenesis.International journal of biological sciences · 2026Article
- Aortic dissection as a disease of vascular wall homeostasis: integrating vasa vasorum-inflammation-metabolism axis for mechanistic insight and clinical translation.Frontiers in immunology · 2026Review
- Inhibition of BMPER Mitigates Pulmonary Hypertension by Modulating LRP1-YAP Interaction in Smooth Muscle Cells.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Fluid Shear Stress-Regulated Vascular Remodeling: Past, Present, and Future.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Endothelial heterogeneity shapes shear stress response: a transcriptomic perspective.Research and practice in thrombosis and haemostasis · 2025Article
- cSTAR analysis identifies endothelial cell cycle as a key regulator of flow-dependent artery remodeling.Science advances · 2025Article
- Microfluidic Perfusable Pathological Vasculature for Atherosclerosis Drug Screening.Research (Washington, D.C.) · 2025Article
- Saving KLF2/4 from γ-protocadherin to reduce vascular inflammation and atherosclerosis.Nature cardiovascular research · 2024Article
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Authors and funding
7 authors.
Funding
Abstract
Vascular remodeling to match arterial diameter to tissue requirements commonly fails in ischemic disease. Endothelial cells sense fluid shear stress (FSS) from blood flow to maintain FSS within a narrow range in healthy vessels. Thus, high FSS induces vessel outward remodeling, but mechanisms are poorly understood. We previously reported that Smad1/5 is maximally activated at physiological FSS. Smad1/5 limits Akt activation, suggesting that inhibiting Smad1/5 may facilitate outward remodeling. Here we report that high FSS suppresses Smad1/5 by elevating KLF2, which induces the bone morphogenetic protein (BMP) pathway inhibitor, BMP-binding endothelial regulator (BMPER), thereby de-inhibiting Akt. In mice, surgically induced high FSS elevated BMPER expression, inactivated Smad1/5 and induced vessel outward remodeling. Endothelial BMPER deletion impaired blood flow recovery and vascular remodeling. Blocking endothelial cell Smad1/5 activation with BMP9/10 blocking antibodies improved vascular remodeling in mouse models of type 1 and type 2 diabetes. Suppression of Smad1/5 is thus a potential therapeutic approach for ischemic disease.
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