ArticleThe Journal of clinical investigation2016
Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 300 papers, 1 of them a synthesis that pooled it.
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Who cites it
300 citing papers in PubMed, 1 synthesis or guideline pooled it, 428 citations in OpenAlex.
- Mapping arterial stiffness metabolic biomarkers: a bibliometric analysis.Frontiers in medicine · 2025Pooled it
- H3K18la in periodontal ligament fibroblasts regulates immune niches and alveolar bone remodeling under mechanical loads.International journal of oral science · 2026Article
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- The microenvironment dictates glyco-immune surveillance via HSF1-mediated metabolism.Science advances · 2026Article
- Mechanobiology-Driven Metabolic Reprogramming: Integrative Roles of YAP/TAZ Signaling and Extracellular Matrix Dynamics.Cell biology international · 2026Review
- Cardiometabolic reprogramming in pulmonary arterial hypertension: Implications for right ventricular dysfunction and therapeutic strategies.Chinese herbal medicines · 2026Review
- From force to fate: Implications of mechanomemory in lung disease.Respiratory research · 2026Review
- Response to Kawamoto et al.EMBO reports · 2026Article
- Mechanical compression causes lung hypoplasia in congenital diaphragmatic hernia with GATA4 genetic variants.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Loss of Endothelial YAP/TAZ Reduces the Size of Chronic Stroke Lesions and Alters the Endothelial Environment.Journal of the American Heart Association · 2026Article
- Glutaminase 1 in Vascular Disease: Linking Metabolic Reprogramming to Atherosclerosis Progression and Stability.Journal of cardiovascular translational research · 2026Review
- Hydrostatic pressure regulates glutamine metabolism to promote bladder fibroblast activation via the Piezo1/YAP1/GLS1 axis.Journal of translational medicine · 2026Article
- The Glutamine-α-Ketoglutarate Metabolic Axis Controls Vascular Smooth Muscle Cell Function.Cells · 2026Article
- A Comprehensive Review of Epigenetic Regulation of Vascular Smooth Muscle Cells During Development and Disease.Biomolecules · 2026Review
- Mechanical regulation of metabolism, epigenetics, and their interplay.npj biomedical innovations · 2026Review
- Sotatercept in Pulmonary Arterial Hypertension: Molecular Mechanisms, Clinical Evidence, and Emerging Role in Reverse Remodelling.International journal of molecular sciences · 2026Review
- Endothelial ADAR1 Deficit Induces the NOCT-IRF7 Axis in Pulmonary Hypertension.Circulation research · 2026Article
- Role and Molecular Mechanisms of Aerobic Glycolysis in Gastrointestinal Tumors.Journal of Cancer · 2026Review
- Mechanobiological Dynamics-Inspired Mechanomodulatory Biomaterials.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
240 more citing papers are in PubMed but not listed here.
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31 authors at 8 institutions in 1 country.
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Abstract
Dysregulation of vascular stiffness and cellular metabolism occurs early in pulmonary hypertension (PH). However, the mechanisms by which biophysical properties of the vascular extracellular matrix (ECM) relate to metabolic processes important in PH remain undefined. In this work, we examined cultured pulmonary vascular cells and various types of PH-diseased lung tissue and determined that ECM stiffening resulted in mechanoactivation of the transcriptional coactivators YAP and TAZ (WWTR1). YAP/TAZ activation modulated metabolic enzymes, including glutaminase (GLS1), to coordinate glutaminolysis and glycolysis. Glutaminolysis, an anaplerotic pathway, replenished aspartate for anabolic biosynthesis, which was critical for sustaining proliferation and migration within stiff ECM. In vitro, GLS1 inhibition blocked aspartate production and reprogrammed cellular proliferation pathways, while application of aspartate restored proliferation. In the monocrotaline rat model of PH, pharmacologic modulation of pulmonary vascular stiffness and YAP-dependent mechanotransduction altered glutaminolysis, pulmonary vascular proliferation, and manifestations of PH. Additionally, pharmacologic targeting of GLS1 in this model ameliorated disease progression. Notably, evaluation of simian immunodeficiency virus-infected nonhuman primates and HIV-infected subjects revealed a correlation between YAP/TAZ-GLS activation and PH. These results indicate that ECM stiffening sustains vascular cell growth and migration through YAP/TAZ-dependent glutaminolysis and anaplerosis, and thereby link mechanical stimuli to dysregulated vascular metabolism. Furthermore, this study identifies potential metabolic drug targets for therapeutic development in PH.
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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.