ArticlePloS one2020
Shear stress-exposed pulmonary artery endothelial cells fail to upregulate HSP70 in chronic thromboembolic pulmonary hypertension.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- Orthogonal microfluidic approaches reveal force-enhanced migration of bacterial populations on surfaces.bioRxiv : the preprint server for biology · 2026Article
- The Research Progress in Targeted Therapy for Hypertension via Heat Shock Proteins.International journal of molecular sciences · 2026Review
- KLF6 activation marks an angiogenic and apoptosis resistant endothelial phenotype in pulmonary arterial hypertension.Communications biology · 2026Article
- Chronic Thromboembolic Pulmonary Hypertension as an Inflammation-Angiogenesis Disorder: From Thrombus Persistence to Dual Pulmonary Vasculopathy.Reviews in cardiovascular medicine · 2026Review
- Flow-driven delivery boosts antibiotic effectiveness by overwhelming bacterial defenses.bioRxiv : the preprint server for biology · 2026Article
- Detoxification of host-relevant HbioRxiv : the preprint server for biology · 2026Article
- HSP70 governs permeability and mechanotransduction in primary human endothelial cells.FEBS open bio · 2026Article
- Flow-induced bending of flagella restrictsmBio · 2026Article
- The Interplay Between Pulmonary Hypertension and Atrial Fibrillation: A Comprehensive Overview.Cells · 2025Review
- Shared genes and relevant potential molecular linkages between COVID-19 and chronic thromboembolic pulmonary hypertension (CTEPH).Journal of thrombosis and thrombolysis · 2025Article
- Microphysiological System-Generated Physiological Shear Forces Reduce TNF-α-Mediated Cartilage Damage in a 3D Model of Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Upfront combination therapy with sildenafil and ambrisentan in patients with chronic thromboembolic pulmonary hypertension.Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia · 2025Article
- Combining multiple stressors blocks bacterial migration and growth.Current biology : CB · 2024Article
- The Importance of Topographical Recognition of Pulmonary Arteries in Diagnostics and Treatment of CTEPH, Based on an Analysis of a Dissected Case Model-A Pilot Study.Diagnostics (Basel, Switzerland) · 2024Article
- Human HSP70-escort protein 1 (hHep1) interacts with negatively charged lipid bilayers and cell membranes.Cell stress & chaperones · 2023Article
- Shear force enhances adhesion ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Shear force enhances adhesion ofbioRxiv : the preprint server for biology · 2023Article
- CD39 in the development and progression of pulmonary arterial hypertension.Purinergic signalling · 2022Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pathophysiological mechanisms underlying chronic thromboembolic pulmonary hypertension (CTEPH) are still unclear. Endothelial cell (EC) remodeling is believed to contribute to this pulmonary disease triggered by thrombus and hemodynamic forces disbalance. Recently, we showed that HSP70 levels decrease by proatherogenic shear stress. Molecular chaperones play a major role in proteostasis in neurological, cancer and inflammatory/ infectious diseases. To shed light on microvascular responses in CTEPH, we characterized the expression of molecular chaperones and annexin A2, a component of the fibrinolytic system. There is no animal model that reproduces microvascular changes in CTEPH, and this fact led us to isolated endothelial cells from patients with CTEPH undergoing pulmonary endarterectomy (PEA). We exposed CTEPH-EC and control human pulmonary endothelial cells (HPAEC) to high- (15 dynes/cm2) or low- (5 dynes/cm2) shear stress. After high-magnitude shear stress HPAEC upregulated heat shock protein 70kDa (HSP70) and the HSP ER paralogs 78 and 94kDa glucose-regulated protein (GRP78 and 94), whereas CTEPH-ECs failed to exhibit this response. At static conditions, both HSP70 and HSP90 families in CTEPH-EC are decreased. Importantly, immunohistochemistry analysis showed that HSP70 expression was downregulated in vivo, and annexin A2 was upregulated. Interestingly, wound healing and angiogenesis assays revealed that HSP70 inhibition with VER-155008 further impaired CTEPH-EC migratory responses. These results implicate HSP70 as a novel master regulator of endothelial dysfunction in type 4 PH. Overall, we first show that global failure of HSP upregulation is a hallmark of CTEPH pathogenesis and propose HSP70 as a potential biomarker of this condition.
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