ArticleJCI insight2016
Distal vessel stiffening is an early and pivotal mechanobiological regulator of vascular remodeling and pulmonary hypertension.
Open access · goldAbstract read
In one paragraph
Article in JCI insight, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
6.7field-weighted citation impact, top 3% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 73 citations in OpenAlex.
- SAF-A/HNRNPU regulates euchromatin dynamics and is required for nuclear envelope integrity.bioRxiv : the preprint server for biology · 2026Article
- Article
- Mechanobiology and Resolution of Lung Fibrosis.Annual review of physiology · 2026Review
- A Brief Overview of Biomechanics and Mechanobiology of the Pulmonary Circulation.Advances in experimental medicine and biology · 2026Review
- Endothelial-smooth muscle microgauges for modeling pulmonary arterial vasoregulation.Lab on a chip · 2025Article
- A soft-stiff patterned bioengineering model reveals kinase pathways driving directional cell migration in pulmonary arterial hypertension.Biomaterials science · 2025Article
- Development of a Novel, Pulmonary Endovascular Device to Treat Patients With Pulmonary Hypertension.Pulmonary circulation · 2025Article
- Female Fibroblast Activation Is Estrogen-Mediated in Sex-Specific 3D-Bioprinted Pulmonary Artery Adventitia Models.ACS biomaterials science & engineering · 2025Article
- Vascular Remodeling: The Multicellular Mechanisms of Pulmonary Hypertension.International journal of molecular sciences · 2025Review
- Tissue-Informed Biomaterial Innovations Advance Pulmonary Regenerative Engineering.ACS macro letters · 2025Review
- Pulmonary Artery Endothelial Cells from Patients with Pulmonary Arterial Hypertension Exhibit Heterogeneous Responses to Their Mechanical Microenvironment.American journal of respiratory cell and molecular biology · 2025Article
- LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Dynamically stiffening biomaterials reveal age- and sex-specific differences in pulmonary arterial adventitial fibroblast activation.Matrix biology plus · 2024Article
- Non-canonical IKB kinases regulate YAP/TAZ and pathological vascular remodeling behaviors in pulmonary artery smooth muscle cells.Physiological reports · 2024Article
- Potential of Current Direct Mechanical Testing Methods in Assessing Intraoperative Samples of Aortic Aneurysm Caused by Uncontrolled Arterial Hypertension.Sovremennye tekhnologii v meditsine · 2024Article
- Article
- 3D-bioprinted, phototunable hydrogel models for studying adventitial fibroblast activation in pulmonary arterial hypertension.Biofabrication · 2022Article
- Cross-talk between TSC2 and the extracellular matrix controls pulmonary vascular proliferation and pulmonary hypertension.Science signaling · 2022Article
- Engineering Hybrid-Hydrogels Comprised of Healthy or Diseased Decellularized Extracellular Matrix to Study Pulmonary Fibrosis.Cellular and molecular bioengineering · 2022Article
- Dichotomous role of integrin-β5 in lung endothelial cells.Pulmonary circulation · 2022Article
Corrections and comments
- Commented on by
Authors and funding
22 authors at 5 institutions in 2 countries.
Fei LiuMolecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
Christina Mallarino HaegerDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Paul B DieffenbachDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Delphine SicardDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA.
Izabela ChrobakLovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
Anna Maria F CoronataDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Margarita M Suárez VelandiaDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Sally VitaliDepartment of Anesthesia, Boston Children's Hospital, Boston, Massachusetts, USA.
Romain A ColasCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Paul C NorrisCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Aleksandar MarinkovićMolecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
Xiaoli LiuDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Jun MaDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Chase D RoseDepartment of Anesthesia, Boston Children's Hospital, Boston, Massachusetts, USA.
Seon-Jin LeeDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Suzy A A ComhairDepartment of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Serpil C ErzurumDepartment of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Jacob D McDonaldLovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
Charles N SerhanCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Stephen R WalshDivision of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Daniel J TschumperlinMolecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA.
Laura E FredenburghDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Brigham and Women's Hospital · USBoston Children's Hospital · USCleveland Clinic Lerner College of Medicine · USLovelace Respiratory Research Institute · USMayo Clinic · US
Funding
Targeting pathological hyaluronan matricesP01HL103453 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI ERZURUM, SERPIL C. · 2011 to 2020
$26.8MRESPIRATORY RESEARCHT32HL007633 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI George R Washko · 1985 to 2026
$14.9MResolution Mechanisms in Acute Inflammation: Resolution PharmacologyP01GM095467 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI LEVY, BRUCE D · 2011 to 2020
$14.8MTraining Program in Molecular and Integrative Physiological SciencesT32HL007118 · NHLBI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI LU, QUAN · 1985 to 2025
$14.3MMesenchymal Stromal Cell Conditioning by Carbon MonoxideP01HL108801 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI CHOI, AUGUSTINE M · 2011 to 2015
$13.8MMechanobiology of Lung FibrosisR01HL092961 · NHLBI · MAYO CLINIC ROCHESTER · PI Daniel J. Tschumperlin · 2009 to 2026
$8.0MAirway redox biochemistry as a deteriminant of asthma phenotype during adolescen*U10HL109250 · NHLBI · UNIVERSITY OF VIRGINIA · PI ERZURUM, SERPIL C., GASTON, BENJAMIN · 2011 to 2016
$4.2MNitric Oxide in Pulmonary HypertensionR37HL060917 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI ERZURUM, SERPIL C. · 2009 to 2018
$3.9MMechanobiology of Vascular Remodeling in Pulmonary Arterial HypertensionR01HL114839 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI FREDENBURGH, LAURA ELIZABETH · 2012 to 2016
$2.1MRole of Cyclooxygenase-2-derived Prostanoids in Polymicrobial SepsisK08GM083207 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI FREDENBURGH, LAURA ELIZABETH · 2008 to 2012
$752kHypoxic inflammation, pulmonary hypertension, and HO-1K08HL077344 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI HARRISON HUNTOON, SALLY H · 2005 to 2009
$643kArterial Stiffness in the Pathogenesis of Human Pulmonary Arterial HypertensionR03HL115106 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI FREDENBURGH, LAURA ELIZABETH · 2012 to 2013
$174kNHLBI NIH HHS F32 HL131228NHLBI NIH HHS K08 HL077344NHLBI NIH HHS P01 HL103453NHLBI NIH HHS P01 HL108801NHLBI NIH HHS R01 HL092961NHLBI NIH HHS R01 HL114839NHLBI NIH HHS R03 HL115106NHLBI NIH HHS R37 HL060917NHLBI NIH HHS T32 HL007118NHLBI NIH HHS T32 HL007633NHLBI NIH HHS U10 HL109250NIGMS NIH HHS K08 GM083207NIGMS NIH HHS P01 GM095467
Abstract
Pulmonary arterial (PA) stiffness is associated with increased mortality in patients with pulmonary hypertension (PH); however, the role of PA stiffening in the pathogenesis of PH remains elusive. Here, we show that distal vascular matrix stiffening is an early mechanobiological regulator of experimental PH. We identify cyclooxygenase-2 (COX-2) suppression and corresponding reduction in prostaglandin production as pivotal regulators of stiffness-dependent vascular cell activation. Atomic force microscopy microindentation demonstrated early PA stiffening in experimental PH and human lung tissue. Pulmonary artery smooth muscle cells (PASMC) grown on substrates with the stiffness of remodeled PAs showed increased proliferation, decreased apoptosis, exaggerated contraction, enhanced matrix deposition, and reduced COX-2-derived prostanoid production compared with cells grown on substrates approximating normal PA stiffness. Treatment with a prostaglandin I
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.